Stuart Goodman, MD, PhD

All Publications

• Sliding Hydrogels Reveal the Modulation of Mechanosensing Attenuates the Inflammatory Phenotype of Osteoarthritic Chondrocytes in 3D. Journal of biomedical materials research. Part A Ayushman, M., Lee, H. P., Agarwal, P., Mikos, G., Tong, X., Jones, S., Sinha, S., Goodman, S., Bhutani, N., Yang, F. 2025; 113 (1): e37861

  Abstract

  Osteoarthritis (OA) is a prevalen degenerative joint disease with no FDA-approved therapies that can halt or reverse its progression. Current treatments address symptoms like pain and inflammation, but not underlying disease mechanisms. OA progression is marked by increased inflammation and extracellular matrix (ECM) degradation of the joint cartilage. While the role of biochemical cues has been widely studied for OA, how matrix mechanical cues influence OA phenotype remains poorly understood. Using sliding hydrogels (SGs) as a tool, we examine how local matrix compliance in 3D modulates OA chondrocyte phenotype and associated mechanosensing. We demonstrate that local matrix compliance reduces the inflammatory phenotype of OA chondrocytes, as indicated by decreased gene expression of catabolic markers and proinflammatory cytokine secretion. This is achieved via significantly reduced nuclear NF-κB expression and signaling in OA chondrocytes. Live cell imaging shows enhanced cellular and nuclear dynamics with increased matrix deformation in the compliant SG. Blocking cellular dynamics negates SG compliance-induced benefits in reducing OA inflammatory phenotype. Further, SG alters nuclear mechanosensing in OA as indicated by increased nuclear lamin reinforcement and chromatin condensation. Finally, we demonstrate that a drug inhibiting histone lysine demethylase to modulate chromatin accessibility reduces OA inflammation in 3D hydrogels. These findings advance our understanding of how ECM mechanics regulate OA mechanobiology and progression and highlight potential disease-modifying treatments via epigenetic and mechanosensing-based therapies.

  View details for DOI 10.1002/jbm.a.37861

  View details for PubMedID 39718447

• Metformin Modulates Cell Oxidative Stress to Mitigate Corticosteroid-Induced Suppression of Osteogenesis in a 3D Model. Journal of inflammation research Cekuc, M. S., Ergul, Y. S., Pius, A. K., Meagan, M., Shinohara, I., Murayama, M., Susuki, Y., Ma, C., Morita, M., Chow, S. K., Bunnell, B. A., Lin, H., Gao, Q., Goodman, S. B. 2024; 17: 10383-10396

  Abstract

  Corticosteroids provide well-established therapeutic benefits; however, they are also accompanied by adverse effects on bone. Metformin is a widely used medication for managing type 2 diabetes mellitus. Recent studies have highlighted additional therapeutic benefits of metformin, particularly concerning bone health and oxidative stress.This research investigates the effects of prednisolone on cellular metabolic functions and bone formation using a 3D in vitro model. Then, we demonstrate the potential therapeutic effects of metformin on oxidative stress and the formation of calcified matrix due to corticosteroids.Human mesenchymal stem cells (MSCs) and macrophages were cultured in a 3D GelMA scaffold and stimulated with prednisolone, with and without metformin. The adverse effects of prednisolone and metformin's therapeutic effect(s) were assessed by analyzing cell viability, osteogenesis markers, bone mineralization, and inflammatory markers. Oxidative stress was measured by evaluating reactive oxygen species (ROS) levels and ATP production.Prednisolone exhibited cytotoxic effects, reducing the viability of MSCs and macrophages. Lower osteogenesis potential was also detected in the MSC group. Metformin positively affected cell functions, including enhanced osteoblast activity and increased bone mineralization. Furthermore, metformin effectively reduced oxidative stress, as evidenced by decreased ROS levels and increased ATP production. These findings indicate that metformin protects against oxidative damage, thus supporting osteogenesis.Metformin exhibits promising therapeutic potential beyond its role in diabetes management. The capacity to alleviate oxidative stress highlights the potential of metformin in supporting bone formation in inflammatory environments.

  View details for DOI 10.2147/JIR.S498888

  View details for PubMedID 39654863

  View details for PubMedCentralID PMC11625639

• Quantification of Empty Lacunae in Tissue Sections of Osteonecrosis of the Femoral Head Using YOLOv8 Artificial Intelligence Model. Journal of biomedical materials research. Part B, Applied biomaterials Shinohara, I., Inui, A., Murayama, M., Susuki, Y., Gao, Q., Chow, S. K., Mifune, Y., Matsumoto, T., Kuroda, R., Goodman, S. B. 2024; 112 (12): e35512

  Abstract

  Histomorphometry is an important technique in the evaluation of non-traumatic osteonecrosis of the femoral head (ONFH). Quantification of empty lacunae and pyknotic cells on histological images is the most reliable measure of ONFH pathology, yet it is time and manpower consuming. This study focused on the application of artificial intelligence (AI) technology to tissue image evaluation. The aim of this study is to establish an automated cell counting platform using YOLOv8 as an object detection model on ONFH tissue images and to evaluate and validate its accuracy. From 30 ONFH model rabbits, 270 tissue images were prepared; based on evaluations by three researchers, ground truth labels were created to classify each cell in the image into two classes (osteocytes and empty lacunae) or three classes (osteocytes, pyknotic cells, and empty lacunae). Two and three classes were then annotated on each image. Transfer learning based on annotated data (80% for training and 20% for validation) was performed using YOLOv8n and YOLOv8x with different parameters. To evaluate the detection accuracy of the training model, the mean average precision (mAP (50)) and precision-recall curve were identified. In addition, the reliability of cell counting by YOLOv8 relative to manual cell counting was evaluated by linear regression analysis using five histological images unused in previous experiments. The mAP (50) for the detection of empty lacunae was 0.868 for the YOLOv8n and 0.883 for the YOLOv8x. The mAP (50) for the three classes was 0.735 for the YOLOv8n model and 0.750 for the YOLOv8x model. The quantification of empty lacunae by automated cell counting obtained in the learning was highly correlated with the manual counting data. The development of an AI-applied automated cell counting platform will significantly reduce the time and effort of manual cell counting in histological analysis.

  View details for DOI 10.1002/jbm.b.35512

  View details for PubMedID 39620323

• Leveraging AI models for lesion detection in osteonecrosis of the femoral head and T1-weighted MRI generation from radiographs. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Shinohara, I., Inui, A., Hwang, K., Murayama, M., Susuki, Y., Uno, T., Gao, Q., Morita, M., Chow, S. K., Tsubosaka, M., Mifune, Y., Matsumoto, T., Kuroda, R., Goodman, S. B. 2024

  Abstract

  This study emphasizes the importance of early detection of osteonecrosis of the femoral head (ONFH) in young patients on long-term glucocorticoid therapy, including those with acute lymphoblastic leukemia, lupus, and other diagnoses. While X-ray and magnetic resonance imaging (MRI) are standard imaging methods for staging ONFH, MRI can be costly and time-consuming. The research focuses on utilizing artificial intelligence (AI) to enhance the evaluation of radiographic images for ONFH detection. The study involved analyzing X-ray and MRI from 102 control hips and 104 ONFH-affected hips at Association Research Circulation Osseous (ARCO) Stage II and IIIa. We employed transfer learning with the YOLOv8 model for object detection, using 80% of the data for training and 20% for validation, then assessed detection accuracy through mean average precision (mAP) and a precision-recall curve. Additionally, AI generated synthetic MRI (sMRI) from X-ray images using a Generative Adversarial Network (GAN) and evaluated their similarity to original MRI. Results showed that the mAP for ONFH detection was 0.923 for the YOLOv8n model and 0.951 for YOLOv8x. The GAN-generated sMRI exhibited lower image quality compared with originals but maintained potential for lesion assessment. Intrarater reliability among evaluators was high. The findings indicate that AI techniques, particularly YOLOv8 for object detection and GAN for image generation, can effectively assist in ONFH screening, despite some limitations in the generated MRI quality.

  View details for DOI 10.1002/jor.26026

  View details for PubMedID 39579026

• The mononuclear phagocyte system obscures the accurate diagnosis of infected joint replacements. Journal of translational medicine Manasherob, R., Warren, S. I., Arora, P., Heo, L., Haddock, N. L., Koliesnik, I., Furukawa, D., Otieno-Ayayo, Z. N., Maloney, W. J., Lowenberg, D. W., Goodman, S. B., Amanatullah, D. F. 2024; 22 (1): 1041

  Abstract

  Diagnosing infected joint replacements relies heavily on assessing the neutrophil response to bacteria. Bacteria form biofilms on joint replacements. Biofilms are sessile bacterial communities encased in a protective extracellular matrix, making them notoriously difficult to culture, remarkably tolerant to antibiotics, and able to evade phagocytosis. Phagocytized bacteria dramatically alter cytokine production and compromise macrophage antigen presentation. We hypothesize that a subset of joint replacements have a dormant infection that suppresses the neutrophil response to bacteria but can be distinguished from uninfected joint replacements by the response of the mononuclear phagocyte system (MPS) within periarticular tissue, synovial fluid, and circulating plasma.Single cell RNASeq transcriptomic and OLink proteomic profiling was performed on matched whole blood, synovial fluid, and periarticular tissue samples collected from 4 joint replacements with an active infection and 3 joint replacements without infection as well as 6 joint replacements with a prior infection deemed "infection-free" by the 2018 Musculoskeletal Infection Society criteria (follow-up of 26 ± 3 months).The MPS and neutrophil responses differ by infected state; the cellular distribution of the MPS response in the subset of joints with dormant infections resembled actively infected joints (p = 0.843, Chi-square test) but was significantly different from uninfected joints (p < 0.001, Chi-square test) despite the absence of systemic acute phase reactants and recruitment of neutrophils (p < 0.001, t-test). When compared to no infection, the cellular composition of dormant infection was distinct. There was reduction in classically activated M1 macrophages (p < 0.001, Fischer's test) and alternatively activated M2 macrophages coupled with an increase in classical monocytes (p < 0.001, Fischer's test), myeloid dendritic cells (p < 0.001, Fischer's test), regulatory T-cells (p < 0.001, Fischer's test), natural killer cells (p = 0.009, Fischer's test), and plasmacytoid dendritic cells (p = 0.005, Fischer's test). Hierarchical cluster analysis and single-cell gene expression revealed that classically M1 and alternatively M2 activated macrophages as well as myeloid dendritic cells can independently distinguish the dormant and uninfected patient populations suggesting that a process that modulates neutrophil recruitment (C1QA, C1QB, LY86, SELL, CXCL5, CCL20, CD14, ITGAM), macrophage polarization (FOSB, JUN), immune checkpoint regulation (IFITM2, IFITM3, CST7, THBS1), and T-cell response (VISIG4, CD28, FYN, LAT2, FCGR3A, CD52) was occurring during dormant infection. Gene set variation analysis suggested that activation of the TNF (FDR < 0.01) and IL17 (FDR < 0.01) pathways may distinguish dormant infections from the active and uninfected populations, while an inactivation of neutrophil extracellular traps (NETs) may be involved in the lack of a clinical response to a dormant infection using established diagnostic criteria. Synovial inflammatory proteomics show an increase in synovial CXCL5 associated with dormant infection (p = 0.011, t-test), suggesting the establishment of a chronic inflammatory state by the MPS during a dormant infection involved in neutrophil inhibition. Plasma inflammatory proteomics also support a chronic inflammatory state (EGF, GZMN, FGF2, PTN, MMP12) during dormant infection that involves a reduction in neutrophil recruitment (CXCL5, p = 0.006, t-test), antigen presentation (LAMP3, p = 0.047, t-test), and T-cell function (CD28, p = 0.045, t-test; CD70, p = 0.002, t-test) that are also seen during the development of bacterial tolerance.All current diagnostic criteria assume each patient can mount the same neutrophil response to an implant-associated infection. However, the state of the MPS is of critical importance to accurate diagnosis of an implant-associated infection. A reduction in neutrophil recruitment and function mediated by the MPS may allow joint replacements with a dormant infection to be mischaracterized as uninfected, thus limiting the prognostic capabilities of all current diagnostic tests.

  View details for DOI 10.1186/s12967-024-05866-5

  View details for PubMedID 39563367

  View details for PubMedCentralID 4887354

• Role of Mitochondrial Complex I in the Proinflammatory Response to Polylactide Implants ACS APPLIED ENGINEERING MATERIALS Maduka, C. V., Makela, A. V., Tundo, A., Ural, E., Stivers, K. B., Alhaj, M., Narayan, R., Goodman, S. B., Ashammakhi, N., Elisseeff, J. H., Hankenson, K. D., Contag, C. H. 2024

  View details for DOI 10.1021/acsaenm.4c00393

  View details for Web of Science ID 001356529200001

• The advantages and shortcomings of stem cell therapy for enhanced bone healing. Tissue engineering. Part C, Methods Chow, S. K., Gao, Q., Pius, A., Morita, M., Ergul, Y. S., Murayama, M., Shinohara, I., Cekuc, M. S., Ma, C., Susuki, Y., Goodman, S. B. 2024

  Abstract

  This review explores the regenerative potential of key progenitor cell types and therapeutic strategies to improve healing of complex fractures and bone defects. We define, summarize, and discuss the differentiation potential of totipotent, pluripotent, and multipotent stem cells, emphasizing the advantages and shortcomings of cell therapy for bone repair and regeneration. The fundamental role of mesenchymal stem cells (MSCs) is highlighted due to their multipotency to differentiate into the key lineage cells including osteoblasts, osteocytes, and chondrocytes, which are crucial for bone formation and remodeling. Hematopoietic stem cells (HSCs) also play a significant role; immune cells such as macrophages and T cells modulate inflammation and tissue repair. Osteoclasts are multi-nucleated cells that are important to bone remodeling. Vascular progenitor cells are critical to oxygen and nutrient supply. The dynamic interplay among these lineages and their microenvironment is essential for effective bone restoration. Therapies involving cells that are more than "minimally manipulated" are controversial and include embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs, derived from early-stage embryos, possess pluripotent capabilities and have shown promise in preclinical studies for bone healing. iPSCs, reprogrammed from somatic cells, offer personalized medicine applications and can differentiate into various tissue-specific cell lines. Minimally manipulative cell therapy approaches such as the use of concentrated bone marrow aspirate (BMAC), exosomes, and various biomaterials for local delivery are explored for their effectiveness in bone regeneration. BMAC, which contains mostly immune cells but few mesenchymal and vascular progenitors, probably improves bone healing by facilitating paracrine mediated intercellular communication. Exosome isolation harnesses the biological signals and cellular byproducts that are a primary source for cell crosstalk and activation. Safe, efficacious, and cost-effective strategies to enhance bone healing using novel cellular therapies are part of a changing paradigm to modulate the inflammatory, repair and regenerative pathways to achieve earlier more robust tissue healing and improved physical function.

  View details for DOI 10.1089/ten.TEC.2024.0252

  View details for PubMedID 39311464

• Author Correction: Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration. Nature communications Andrew, T. W., Koepke, L. S., Wang, Y., Lopez, M., Steininger, H., Struck, D., Boyko, T., Ambrosi, T. H., Tong, X., Sun, Y., Gulati, G. S., Murphy, M. P., Marecic, O., Tevlin, R., Schallmoser, K., Strunk, D., Seita, J., Goodman, S. B., Yang, F., Longaker, M. T., Yang, G. P., Chan, C. K. 2024; 15 (1): 8030

  View details for DOI 10.1038/s41467-024-51829-1

  View details for PubMedID 39271692

• The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration. Bone & joint research Murayama, M., Chow, S. K., Lee, M. L., Young, B., Ergul, Y. S., Shinohara, I., Susuki, Y., Toya, M., Gao, Q., Goodman, S. B. 2024; 13 (9): 462-473

  Abstract

  Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes - the main cellular components in BMAC - interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

  View details for DOI 10.1302/2046-3758.139.BJR-2024-0122.R1

  View details for PubMedID 39237112

• Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches. Immunity & ageing : I & A Zhang, N., Zhai, L., Wong, R. M., Cui, C., Law, S. W., Chow, S. K., Goodman, S. B., Cheung, W. H. 2024; 21 (1): 55

  Abstract

  Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

  View details for DOI 10.1186/s12979-024-00458-9

  View details for PubMedID 39103919

  View details for PubMedCentralID 3118623

• MANAGEMENT OF ACETABULAR OSTEOLYSIS WITH A RETAINED SHELL AND INJECTION OF DEMINERALIZED BONE MATRIX USING A VINYL URINARY CATHETER AND SYRINGE: A NEW TECHNIQUE AND CASE SERIES Apinyankul, R., Silva, L., Goodman, S. SPRINGER. 2024: S509-S510

  View details for Web of Science ID 001363175503353

• The Influence of an Unexpected Symbolic Gift on Postoperative Arthroplasty Patients' Press Ganey Scores. The Journal of arthroplasty Lee, J. J., Mitchell, A. R., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2024

  Abstract

  INTRODUCTION: Hospitals use Press Ganey surveys to evaluate patient satisfaction. The goal of our study was to evaluate whether surgeon-driven gifting to patients post-operatively affects Press Ganey Survey responses.METHODS: There were 1,468 patients undergoing arthroplasty at our institution who were randomized to receive a thank you gift, a small bouquet of flowers, and a note from their provider after surgery, or nothing for completing their pre-operative arthroplasty registry questionnaire. Press Ganey surveys were sent to patients who received and did not receive flowers immediately after their hospital stay and after the patients' first post-operative visit. Scores were reported as the mean score and the fraction of responses with a top-box rating. One-sided student t-tests and Fischer Exact tests were used to assess statistical significance.RESULTS: Hospital Discharge Patients who received flowers had higher Press Ganey survey scores than patients who did not receive flowers. For example, for "Physician's concerns for questions," they had higher scores (mean difference: 3.7 ± 1.6 points, P = 0.012) and a 9% higher top-box rating (P = 0.032). For "Staff attitude towards visitors," they also had higher scores (mean difference: 2.8 ± 1.3 points, P = 0.019) and a 7% higher top-box rating (P = 0.049). First Follow-up Patients who received flowers had a higher top-box rating for "Concern provider showed for questions" and "Amount of time provider spent with you" by 6% (P = 0.046) and 11% (P = 0.009), respectively. They also had higher scores for "Information provider gave about medications" (mean difference: 4.0 ± 1.6 points, P = 0.009) and 11% higher top-box rating (P = 0.006).DISCUSSION: Press Ganey Surveys were higher in orthopaedic patients who received bouquets of flowers from their arthroplasty surgeons compared to patients who did not. At follow-up, improved Press Ganey scores persisted if the patient received flowers. The gift of flowers generates patient loyalty to their surgeon.

  View details for DOI 10.1016/j.arth.2024.07.018

  View details for PubMedID 39025277

• T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells. Journal of biomedical materials research. Part A Murayama, M., Shinohara, I., Toya, M., Susuki, Y., Lee, M. L., Young, B., Gao, Q., Chow, S. K., Goodman, S. B. 2024

  Abstract

  Approximately 5%-10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA-approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti-inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC-based therapies.

  View details for DOI 10.1002/jbm.a.37771

  View details for PubMedID 38963690

• The outcome of revision total hip arthroplasty for instability. The bone & joint journal Apinyankul, R., Hong, C., Hwang, K. L., Burket Koltsov, J. C., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2024; 106-B (5 Supple B): 105-111

  Abstract

  Instability is a common indication for revision total hip arthroplasty (THA). However, even after the initial revision, some patients continue to have recurrent dislocation. The aim of this study was to assess the risk for recurrent dislocation after revision THA for instability.Between 2009 and 2019, 163 patients underwent revision THA for instability at Stanford University Medical Center. Of these, 33 (20.2%) required re-revision due to recurrent dislocation. Cox proportional hazard models, with death and re-revision surgery for periprosthetic infection as competing events, were used to analyze the risk factors, including the size and alignment of the components. Paired t-tests or Wilcoxon signed-rank tests were used to assess the outcome using the Veterans RAND 12 (VR-12) physical and VR-12 mental scores, the Harris Hip Score (HHS) pain and function, and the Hip disability and Osteoarthritis Outcome score for Joint Replacement (HOOS, JR).The median follow-up was 3.1 years (interquartile range 2.0 to 5.1). The one-year cumulative incidence of recurrent dislocation after revision was 8.7%, which increased to 18.8% at five years and 31.9% at ten years postoperatively. In multivariable analysis, a high American Society of Anesthesiologists (ASA) grade (hazard ratio (HR) 2.72 (95% confidence interval (CI) 1.13 to 6.60)), BMI between 25 and 30 kg/m2 (HR 4.31 (95% CI 1.52 to 12.27)), the use of specialized liners (HR 5.39 (95% CI 1.97 to 14.79) to 10.55 (95% CI 2.27 to 49.15)), lumbopelvic stiffness (HR 6.03 (95% CI 1.80 to 20.23)), and postoperative abductor weakness (HR 7.48 (95% CI 2.34 to 23.91)) were significant risk factors for recurrent dislocation. Increasing the size of the acetabular component by > 1 mm significantly decreased the risk of dislocation (HR 0.89 (95% CI 0.82 to 0.96)). The VR-12 physical and HHS (pain and function) scores improved significantly at mid term.Patients requiring revision THA for instability are at risk of recurrent dislocation. Higher ASA grades, being overweight, a previous lumbopelvic fusion, the use of specialized liners, and postoperative abductor weakness are significant risk factors.

  View details for DOI 10.1302/0301-620X.106B5.BJJ-2023-0726.R1

  View details for PubMedID 38688516

• Correction: Pius et al. Effects of Aging on Osteosynthesis at Bone-Implant Interfaces. Biomolecules 2024, 14, 52. Biomolecules Pius, A. K., Toya, M., Gao, Q., Lee, M. L., Ergul, Y. S., Chow, S. K., Goodman, S. B. 2024; 14 (3)

  Abstract

  Max L. Lee was not included as an author in the original publication [...].

  View details for DOI 10.3390/biom14030340

  View details for PubMedID 38540803

• Targeting an inflammation-amplifying cell population can attenuate osteoarthritis-associated pain. Arthritis research & therapy Pandey, A., Singla, M., Geller, A., Goodman, S. B., Bhutani, N. 2024; 26 (1): 53

  Abstract

  BACKGROUND: Understanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade.METHODS: In this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice.RESULTS: Modulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants.CONCLUSION: These studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.

  View details for DOI 10.1186/s13075-024-03284-y

  View details for PubMedID 38368390

• Assessing Ability for ChatGPT to Answer Total Knee Arthroplasty-Related Questions. The Journal of arthroplasty Magruder, M. L., Rodriguez, A., Wong, C. H., Erez, O., Piuzzi, N. S., Scuderi, G. R., Slover, J., Oh, J. H., Schwarzkopf, R., Chen, A. F., Iorio, R., Goodman, S. B., Mont, M. A. 2024

  Abstract

  Artificial intelligence (AI) in the field of orthopaedics has been a topic of increasing interest and opportunity in recent years. Its applications are widespread both for physicians and patients, including use in clinical decision-making, in the operating room, and in research. In this study, we aimed to assess the quality of ChatGPT answers when asked questions related to total knee arthroplasty (TKA).ChatGPT prompts were created by turning 15 of the American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice Guidelines into questions. An online survey was created, which included screenshots of each prompt and answers to the 15 questions. Surgeons were asked to grade ChatGPT answers from 1 to 5 based on their characteristics: 1) Relevance; 2) Accuracy; 3) Clarity; 4) Completeness; 5) Evidence-based; and 6) Consistency. There were eleven Adult Joint Reconstruction fellowship-trained surgeons who completed the survey. Questions were subclassified based on the subject of the prompt: 1) risk factors, 2) implant/Intraoperative, and 3) pain/functional outcomes. The average and standard deviation for all answers, as well as for each subgroup, were calculated. Inter-rater reliability (IRR) was also calculated.All answer characteristics were graded as being above average (i.e., a score > 3). Relevance demonstrated the highest scores (4.43±0.77) by surgeons surveyed, and consistency demonstrated the lowest scores (3.54±1.10). ChatGPT prompts in the Risk Factors group demonstrated the best responses, while those in the Pain/Functional Outcome group demonstrated the lowest. The overall IRR was found to be 0.33 (poor reliability), with the highest IRR for relevance (0.43) and the lowest for evidence-based (0.28).ChatGPT can answer questions regarding well-established clinical guidelines in TKA with above-average accuracy but demonstrates variable reliability. This investigation is the first step in understanding large language model (LLM) AIs like ChatGPT and how well they perform in the field of arthroplasty.

  View details for DOI 10.1016/j.arth.2024.02.023

  View details for PubMedID 38364879

• Additively manufactured Ti-Ta-Cu alloys for the next-generation load-bearing implants. International journal of extreme manufacturing Bandyopadhyay, A., Mitra, I., Ciliveri, S., Avila, J. D., Dernell, W., Goodman, S. B., Bose, S. 2024; 6 (1): 015503

  Abstract

  Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum (Ta)-Copper (Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological, mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta (10Ta) and 3 wt.% Cu (3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e. 78%-86% with respect to CpTi. Mechanical properties for Ti3Al2V-10Ta-3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with 10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse inflammatory response in vivo. Our results establish the Ti3Al2V-10Ta-3Cu alloy's synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

  View details for DOI 10.1088/2631-7990/ad07e7

  View details for PubMedID 38021398

  View details for PubMedCentralID PMC10654690

• Sex differences of NF-κB-targeted therapy for mitigating osteoporosis associated with chronic inflammation of bone. Bone & joint research Toya, M., Kushioka, J., Shen, H., Utsunomiya, T., Hirata, H., Tsubosaka, M., Gao, Q., Chow, S. K., Zhang, N., Goodman, S. B. 2024; 13 (1): 28-39

  Abstract

  Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN.We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males.

  View details for DOI 10.1302/2046-3758.131.BJR-2023-0040.R3

  View details for PubMedID 38194999

• Preclinical models for studying corticosteroid-induced osteonecrosis of the femoral head. Journal of biomedical materials research. Part B, Applied biomaterials Tsubosaka, M., Maruyama, M., Lui, E., Kushioka, J., Toya, M., Gao, Q., Shen, H., Li, X., Chow, S. K., Zhang, N., Yang, Y. P., Goodman, S. B. 2024; 112 (1): e35360

  Abstract

  Nontraumatic osteonecrosis of the femoral head (ONFH) is a refractory condition that commonly results in femoral head collapse and degenerative arthritis of the hip. In the early stages, surgical procedures for hip preservation, including core decompression (CD), have been developed to prevent progressive collapse of the femoral head. Optimization of bone regeneration and biological augmentation may further enhance the therapeutic efficacy of CD for ONFH. Thus, combining CD with cell-based therapy has recently been proposed. In fact, patients treated with cell-based therapy using autologous bone marrow concentrate demonstrate improved survivorship of the femoral head, compared with conventional CD alone. Preclinical research studies to investigate adjunctive therapies for CD often utilize the rabbit model of corticosteroid-induced ONFH. Mesenchymal stem cells (MSCs) are known to promote osteogenesis and angiogenesis, and decrease inflammation in bone. Local drug delivery systems have the potential to achieve targeted therapeutic effects by precisely controlling the drug release rate. Scaffolds can provide an osteoconductive structural framework to facilitate the repair of osteonecrotic bone tissue. We focused on the combination of both cell-based and scaffold-based therapies for bone tissue regeneration in ONFH. We hypothesized that combining CD and osteoconductive scaffolds would provide mechanical strength and structural cell guidance; and that combining CD and genetically modified (GM) MSCs to express relevant cytokines, chemokines, and growth factors would promote bone tissue repair. We developed GM MSCs that overexpress the anti-inflammatory, pro-reconstructive cytokines platelet-derived growth factor-BB to provide MSCs with additional benefits and investigated the efficacy of combinations of these GM MSCs and scaffolds for treatment of ONFH in skeletally mature male New Zealand white rabbits. In the future, the long-term safety, efficacy, durability, and cost-effectiveness of these and other biological and mechanical treatments must be demonstrated for the patients affected by ONFH.

  View details for DOI 10.1002/jbm.b.35360

  View details for PubMedID 38247252

• Preclinical models for studying corticosteroid-induced osteonecrosis of the femoral head JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Tsubosaka, M., Maruyama, M., Lui, E., Kushioka, J., Toya, M., Gao, Q., Shen, H., Li, X., Chow, S., Zhang, N., Yang, Y., Goodman, S. B. 2024; 112 (1)

  View details for DOI 10.1002/jbm.b.35360

  View details for Web of Science ID 001129268300001

• Effects of Aging on Osteosynthesis at Bone-Implant Interfaces. Biomolecules Pius, A. K., Toya, M., Gao, Q., Ergul, Y. S., Chow, S. K., Goodman, S. B. 2023; 14 (1)

  Abstract

  Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.

  View details for DOI 10.3390/biom14010052

  View details for PubMedID 38254652

• The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Schwarz, E. M., Archer, N. K., Atkins, G. J., Bentley, K. a., Botros, M., Cassat, J. E., Chisari, E., Coraça-Huber, D. C., Daiss, J. L., Gill, S. R., Goodman, S. B., Harro, J., Hernandez, C. J., Ivashkiv, L. B., Kates, S. L., Marques, C. N., Masters, E. A., Muthukrishnan, G., Owen, J. R., Raafat, D., Saito, M., Veis, D. J., Xie, C. 2023

  Abstract

  Musculoskeletal infections (MSKI), which are a major problem in orthopedics, occur when the pathogen eludes or overwhelms the host immune system. While effective vaccines and immunotherapies to prevent and treat MSKI should be possible, fundamental knowledge gaps in our understanding of protective, nonprotective, and pathogenic host immunity are prohibitive. We also lack critical knowledge of how host immunity is affected by the microbiome, implants, prior infection, nutrition, antibiotics, and concomitant therapies, autoimmunity, and other comorbidities. To define our current knowledge of these critical topics, a Host Immunity Section of the 2023 Orthopaedic Research Society MSKI International Consensus Meeting (ICM) proposed 78 questions. Systematic reviews were performed on 15 of these questions, upon which recommendations with level of evidence were voted on by the 72 ICM delegates, and another 12 questions were voted on with a recommendation of "Unknown" without systematic reviews. Two questions were transferred to another ICM Section, and the other 45 were tabled for future consideration due to limitations of available human resources. Here we report the results of the voting with internet access to the questions, recommendations, and rationale from the systematic reviews. Eighteen questions received a consensus vote of ≥90%, while nine recommendations failed to achieve this threshold. Commentary on why consensus was not achieved on these questions and potential ways forward are provided to stimulate specific funding mechanisms and research on these critical MSKI host defense questions.

  View details for DOI 10.1002/jor.25758

  View details for PubMedID 38102985

• Primary Total Hip Arthroplasty in Juvenile Idiopathic Arthritis: Survivorship after a Median Follow-up of 12 Years. The Journal of arthroplasty Warren, S. I., Hwang, K. L., Lee, J. J., Murrietta, A., Koltsov, J. C., Goodman, S. B. 2023

  Abstract

  Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition of childhood that frequently affects the hip. Total hip arthroplasty (THA) in JIA can be challenging due to the patient's young age, small proportion, complex anatomy, and bone loss. Outcome data is limited.We reviewed prospectively collected data in 57 JIA patients (83 hips) who underwent THA between 1986 and 2020 by a single surgeon. The median patient age at surgery was 26 years (range, 14 to 62). Reoperation-free survival was assessed via the cumulative incidence function, accounting for the competing risk of death. Relationships between patient and implant factors and survivorship were evaluated by stratification of the cumulative incidence function and Gray's tests. Wilcoxon signed rank tests were used to assess the preoperative to latest postoperative change in patient reported outcomes measures (PROMs).At a median (interquartile range) of 12 (4, 20) years follow-up, 13 (16%) patients underwent reoperation, most commonly for polyethylene wear and osteolysis (7 hips). The estimated incidence of 10-, 20-, and 30-year revision (95% confidence interval) were 11.3% (4.5, 21.6%), 18.5% (8.9, 30.9%), and 40.6% (19.4, 60.9%), respectively. There were no differences in survival based on patient age, sex, implant fixation method, polyethylene type, or thickness. All PROMs improved from preoperative to latest follow up.Primary THA is a durable and effective treatment for JIA patients with severe hip involvement and results in major improvements in pain and function. We did not identify any factors predictive of failure.

  View details for DOI 10.1016/j.arth.2023.12.021

  View details for PubMedID 38104785

• Host and Microbial Characteristics Associated with Recurrent Prosthetic Joint Infections. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Hampton, J. P., Zhou, J. Y., Kameni, F. N., Espiritu, J. R., Manasherob, R., Cheung, E., Miller, M. D., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2023

  Abstract

  Approximately 20% of patients after resection arthroplasty and antibiotic spacer placement for prosthetic joint infection develop repeat infections, requiring an additional antibiotic spacer before definitive reimplantation. The host and bacterial characteristics associated with the development of recurrent infection is poorly understood. A case-control study was conducted for 106 patients with intention to treat by two-stage revision arthroplasty for prosthetic joint infection at a single institution between 2009-2020. Infection was defined according to the 2018 Musculoskeletal Infection Society criteria. Thirty-nine cases ("recurrent-PJI") received at least two antibiotic spacers before clinical resolution of their infection, and 67 controls ("single-PJI") received a single antibiotic cement spacer prior to infection-free prosthesis reimplantation. Patient demographics, McPherson host grade, and culture results including antibiotic susceptibilities were compared. Fifty-two (78%) single-PJI and 32 (82%) recurrent-PJI patients had positive intraoperative cultures at the time of their initial spacer procedure. The odds of polymicrobial infections were 11-fold higher among recurrent-PJI patients, and the odds of significant systemic compromise (McPherson host-grade C) were more than double. Recurrent-PJI patients were significantly more likely to harbor Staphylococcus aureus. We found no differences between cases and controls in pathogen resistance to the six most tested antibiotics. Among recurrent-PJI patients, erythromycin-resistant infections were more prevalent at the final than initial spacer, despite no erythromycin exposure. Our findings suggest that McPherson host grade, polymicrobial infection, and S. aureus infection are key indicators of secondary or persistent joint infection following resection arthroplasty and antibiotic spacer placement, while bacterial resistance does not predict infection-related arthroplasty failure. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.25768

  View details for PubMedID 38093490

• C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration. Biomolecules Shinohara, I., Tsubosaka, M., Toya, M., Lee, M. L., Kushioka, J., Murayama, M., Gao, Q., Li, X., Zhang, N., Chow, S. K., Matsumoto, T., Kuroda, R., Goodman, S. B. 2023; 13 (11)

  Abstract

  Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2-overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

  View details for DOI 10.3390/biom13111665

  View details for PubMedID 38002347

• Polylactide Degradation Activates Immune Cells by Metabolic Reprogramming. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Maduka, C. V., Alhaj, M., Ural, E., Habeeb, O. M., Kuhnert, M. M., Smith, K., Makela, A. V., Pope, H., Chen, S., Hix, J. M., Mallett, C. L., Chung, S., Hakun, M., Tundo, A., Zinn, K. R., Hankenson, K. D., Goodman, S. B., Narayan, R., Contag, C. H. 2023: e2304632

  Abstract

  Polylactide (PLA) is the most widely utilized biopolymer in medicine. However, chronic inflammation and excessive fibrosis resulting from its degradation remain significant obstacles to extended clinical use. Immune cell activation has been correlated to the acidity of breakdown products, yet methods to neutralize the pH have not significantly reduced adverse responses. Using a bioenergetic model, delayed cellular changes are observed that are not apparent in the short-term. Amorphous and semi-crystalline PLA degradation products, including monomeric l-lactic acid, mechanistically remodel metabolism in cells leading to a reactive immune microenvironment characterized by elevated proinflammatory cytokines. Selective inhibition of metabolic reprogramming and altered bioenergetics both reduce these undesirable high cytokine levels and stimulate anti-inflammatory signals. The results present a new biocompatibility paradigm by identifying metabolism as a target for immunomodulation to increase tolerance to biomaterials, ensuring safe clinical application of PLA-based implants for soft- and hard-tissue regeneration, and advancing nanomedicine and drug delivery.

  View details for DOI 10.1002/advs.202304632

  View details for PubMedID 37737614

• Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials. Journal of biomedical materials research. Part A Gibon, E., Takakubo, Y., Zwingenberger, S., Gallo, J., Takagi, M., Goodman, S. B. 2023

  Abstract

  The use of biomaterials and implants for joint replacement, fracture fixation, spinal stabilization and other orthopedic indications has revolutionized patient care by reliably decreasing pain and improving function. These surgical procedures always invoke an acute inflammatory reaction initially, that in most cases, readily subsides. Occasionally, chronic inflammation around the implant develops and persists; this results in unremitting pain and compromises function. The etiology of chronic inflammation may be specific, such as with infection, or be unknown. The histological hallmarks of chronic inflammation include activated macrophages, fibroblasts, T cell subsets, and other cells of the innate immune system. The presence of cells of the adaptive immune system usually indicates allergic reactions to metallic haptens. A foreign body reaction is composed of activated macrophages, giant cells, fibroblasts, and other cells often distributed in a characteristic histological arrangement; this reaction is usually due to particulate debris and other byproducts from the biomaterials used in the implant. Both chronic inflammation and the foreign body response have adverse biological effects on the integration of the implant with the surrounding tissues. Strategies to mitigate chronic inflammation and the foreign body response will enhance the initial incorporation and longevity of the implant, and thereby, improve long-term pain relief and overall function for the patient. The seminal research performed in the laboratory of Dr. James Anderson and co-workers has provided an inspirational and driving force for our laboratory's work on the interactions and crosstalk among cells of the mesenchymal, immune, and vascular lineages, and orthopedic biomaterials. Dr. Anderson's delineation of the fundamental biologic processes and mechanisms underlying acute and chronic inflammation, the foreign body response, resolution, and eventual functional integration of implants in different organ systems has provided researchers with a strategic approach to the use of biomaterials to improve health in numerous clinical scenarios.

  View details for DOI 10.1002/jbm.a.37599

  View details for PubMedID 37656958

• TET1 regulates skeletal stem cell (SSC) mediated cartilage regeneration. Arthritis & rheumatology (Hoboken, N.J.) Pandey, A., Hoover, M., Singla, M., Bedi, Y., Storaci, H., Goodman, S. B., Chan, C., Bhutani, N. 2023

  Abstract

  Adult skeletal stem cells (SSC) give rise to chondrocytes, osteocytes and stromal cells as progeny have been shown to contribute to cartilage regeneration in Osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase, TET1 regulates SSC function in OA.We investigated the differences in SSC lineage tree and differentiation potential in neonatal and adult Tet1 +/+ and Tet1-/- mice, with and without injury and upon OA induction and progression. Using RNA-seq, the transcriptomic differences between SSC and Bone, cartilage and stromal progenitor cells (BCSP) were identified in Tet1 +/+ mice and Tet1-/- mice.Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSC and BCSP. Tet1 inhibition led to enhanced chondrogenesis in in human SSC and chondroprogenitors (CP) isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of Osteoarthritis (OA) led to increased cartilage regeneration. Transcriptomic analyses of SSC and BCSP lacking Tet1 revealed pathway alterations in TGFβ signaling, melatonin degradation and cartilage development associated genes. Lastly, we report that use of hormone melatonin can dampen inflammation and improve cartilage health.While Tet1 is a broad epigenetic regulator, Melatonin can mimic the ability of TET1 inhibition to enhance the chondrogenic ability of skeletal stem cells. Melatonin administration has the potential to be an attractive stem cell based therapy for cartilage regeneration.

  View details for DOI 10.1002/art.42678

  View details for PubMedID 37610277

• Glycolytic reprogramming in macrophages and MSCs during inflammation. Frontiers in immunology Li, X., Shen, H., Zhang, M., Teissier, V., Huang, E. E., Gao, Q., Tsubosaka, M., Toya, M., Kushioka, J., Maduka, C. V., Contag, C. H., Chow, S. K., Zhang, N., Goodman, S. B. 2023; 14: 1199751

  Abstract

  Dysregulated inflammation is associated with many skeletal diseases and disorders, such as osteolysis, non-union of fractures, osteonecrosis, osteoarthritis and orthopaedic infections. We previously showed that continuous infusion of lipopolysaccharide (LPS) contaminated polyethylene particles (cPE) caused prolonged inflammation and impaired bone formation. However, the metabolic and bioenergetic processes associated with inflammation of bone are unknown. Mitochondria are highly dynamic organelles that modulate cell metabolism and orchestrate the inflammatory responses that involve both resident and recruited cells. Glycolytic reprogramming, the shift from oxidative phosphorylation (OXPHOS) to glycolysis causes inappropriate cell activation and function, resulting in dysfunctional cellular metabolism. We hypothesized that impaired immunoregulation and bone regeneration from inflammatory states are associated with glycolytic reprogramming and mitochondrial dysfunction in macrophages (Mφ) and mesenchymal stromal cells (MSCs).We used the Seahorse XF96 analyzer and real-time qPCR to study the bioenergetics of Mφ and MSCs exposed to cPE. To understand the oxygen consumption rate (OCR), we used Seahorse XF Cell Mito Stress Test Kit with Seahorse XF96 analyzer. Similarly, Seahorse XF Glycolytic Rate Assay Kit was used to detect the extracellular acidification rate (ECAR) and Seahorse XF Real-Time ATP Rate Assay kit was used to detect the real-time ATP production rates from OXPHOS and glycolysis. Real-time qPCR was performed to analyze the gene expression of key enzymes in glycolysis and mitochondrial biogenesis. We further detected the gene expression of proinflammatory cytokines in Mφ and genes related to cell differentiation in MSC during the challenge of cPE.Our results demonstrated that the oxidative phosphorylation of Mφ exposed to cPE was significantly decreased when compared with the control group. We found reduced basal, maximal and ATP-production coupled respiration rates, and decreased proton leak in Mφ during challenge with cPE. Meanwhile, Mφ showed increased basal glycolysis and proton efflux rates (PER) when exposed to cPE. The percentage (%) of PER from glycolysis was higher in Mφ exposed to cPE, indicating that the contribution of the glycolytic pathway to total extracellular acidification was elevated during the challenge of cPE. In line with the results of OCR and ECAR, we found Mφ during cPE challenge showed higher glycolytic ATP (glycoATP) production rates and lower mitochondrial ATP (mitoATP) production rates which is mainly from OXPHOS. Interestingly, MSCs showed enhanced glycolysis during challenge with cPE, but no significant changes in oxygen consumption rates (OCR). In accordance, seahorse assay of real-time ATP revealed glycoATP rates were elevated while mitoATP rates showed no significant differences in MSC during challenge with cPE. Furthermore, Mφ and MSCs exposed to cPE showed upregulated gene expression levels of glycolytic regulators and Mφ exposed to cPE expressed higher levels of pro-inflammatory cytokines.This study demonstrated the dysfunctional bioenergetic activity of bone marrow-derived Mφ and MSCs exposed to cPE, which could impair the immunoregulatory properties of cells in the bone niche. The underlying molecular defect related to disordered mitochondrial function could represent a potential therapeutic target during the resolution of inflammation.

  View details for DOI 10.3389/fimmu.2023.1199751

  View details for PubMedID 37675119

  View details for PubMedCentralID PMC10477714

• Del1 Is a Growth Factor for Skeletal Progenitor Cells in the Fracture Callus. Biomolecules Sun, Y., Boyko, T., Marecic, O., Struck, D., Mann, R. K., Andrew, T. W., Lopez, M., Tong, X., Goodman, S. B., Yang, F., Longaker, M. T., Chan, C. K., Yang, G. P. 2023; 13 (8)

  Abstract

  Failure to properly form bone or integrate surgical implants can lead to morbidity and additional surgical interventions in a significant proportion of orthopedic surgeries. While the role of skeletal stem cells (SSCs) in bone formation and repair is well-established, very little is known about the factors that regulate the downstream Bone, Cartilage, Stromal, Progenitors (BCSPs). BCSPs, as transit amplifying progenitor cells, undergo multiple mitotic divisions to expand the pool of lineage committed progenitors allowing stem cells to preserve their self-renewal and stemness. Del1 is a protein widely expressed in the skeletal system, but its deletion led to minimal phenotype changes in the uninjured mouse. In this paper, we demonstrate that Del1 is a key regulator of BCSP expansion following injury. In Del1 knockout mice, there is a significant reduction in the number of BCSPs which leads to a smaller callus and decreased bone formation compared with wildtype (WT) littermates. Del1 serves to promote BCSP proliferation and prevent apoptosis in vivo and in vitro. Moreover, exogenous Del1 promotes proliferation of aged human BCSPs. Our results highlight the potential of Del1 as a therapeutic target for improving bone formation and implant success. Del1 injections may improve the success of orthopedic surgeries and fracture healing by enhancing the proliferation and survival of BCSPs, which are crucial for generating new bone tissue during the process of bone formation and repair.

  View details for DOI 10.3390/biom13081214

  View details for PubMedID 37627279

• CCL2 promotes osteogenesis by facilitating macrophage migration during acute inflammation. Frontiers in cell and developmental biology Toya, M., Zhang, N., Tsubosaka, M., Kushioka, J., Gao, Q., Li, X., Chow, S. K., Goodman, S. B. 2023; 11: 1213641

  Abstract

  Novel minimally invasive strategies are needed to obtain robust bone healing in complex fractures and bone defects in the elderly population. Local cell therapy is one potential option for future treatment. Mesenchymal stromal cells (MSCs) are not only involved in osteogenesis but also help direct the recruitment of macrophages during bone regeneration via MSC-macrophage crosstalk. The C-C motif chemokine ligand 2 (CCL2) is an inflammatory chemokine that is associated with the migration of macrophages and MSCs during inflammation. This study investigated the use of CCL2 as a therapeutic target for local cell therapy. MSCs and macrophages were isolated from 10 to 12 week-old BALB/c male mice. Genetically modified CCL2 over-expressing MSCs were produced using murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture. Cell migration assays were also performed. MSCs transfected with murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector showed higher levels of CCL2 secretion compared to unaltered MSCs (p < 0.05). Genetic manipulation did not affect cell proliferation. CCL2 did not affect the osteogenic ability of MSCs alone. However, acute (1 day) but not sustained (7 days) stimulation with CCL2 increased the alizarin red-positive area when MSCs were co-cultured with macrophages (p < 0.001). Both recombinant CCL2 (p < 0.05) and CCL2 released from MSCs (p < 0.05) facilitated macrophage migration. We demonstrated that acute CCL2 stimulation promoted subsequent osteogenesis in co-culture of MSCs and macrophages. Acute CCL2 stimulation potentially facilitates osteogenesis during the acute inflammatory phase of bone healing by directing local macrophage migration, fostering macrophage-MSC crosstalk, and subsequently, by activating or licensing of MSCs by macrophage pro-inflammatory cytokines. The combination of CCL2, MSCs, and macrophages could be a potential strategy for local cell therapy in compromised bone healing.

  View details for DOI 10.3389/fcell.2023.1213641

  View details for PubMedID 37457301

  View details for PubMedCentralID PMC10348816

• Purification and functional characterization of novel human skeletal stem cell lineages. Nature protocols Hoover, M. Y., Ambrosi, T. H., Steininger, H. M., Koepke, L. S., Wang, Y., Zhao, L., Murphy, M. P., Alam, A. A., Arouge, E. J., Butler, M. G., Takematsu, E., Stavitsky, S. P., Hu, S., Sahoo, D., Sinha, R., Morri, M., Neff, N., Bishop, J., Gardner, M., Goodman, S., Longaker, M., Chan, C. K. 2023

  Abstract

  Human skeletal stem cells (hSSCs) hold tremendous therapeutic potential for developing new clinical strategies to effectively combat congenital and age-related musculoskeletal disorders. Unfortunately, refined methodologies for the proper isolation of bona fide hSSCs and the development of functional assays that accurately recapitulate their physiology within the skeleton have been lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs), commonly used to describe the source of precursors for osteoblasts, chondrocytes, adipocytes and stroma, have held great promise as the basis of various approaches for cell therapy. However, the reproducibility and clinical efficacy of these attempts have been obscured by the heterogeneous nature of BMSCs due to their isolation by plastic adherence techniques. To address these limitations, our group has refined the purity of individual progenitor populations that are encompassed by BMSCs by identifying defined populations of bona fide hSSCs and their downstream progenitors that strictly give rise to skeletally restricted cell lineages. Here, we describe an advanced flow cytometric approach that utilizes an extensive panel of eight cell surface markers to define hSSCs; bone, cartilage and stromal progenitors; and more differentiated unipotent subtypes, including an osteogenic subset and three chondroprogenitors. We provide detailed instructions for the FACS-based isolation of hSSCs from various tissue sources, in vitro and in vivo skeletogenic functional assays, human xenograft mouse models and single-cell RNA sequencing analysis. This application of hSSC isolation can be performed by any researcher with basic skills in biology and flow cytometry within 1-2 days. The downstream functional assays can be performed within a range of 1-2 months.

  View details for DOI 10.1038/s41596-023-00836-5

  View details for PubMedID 37316563

  View details for PubMedCentralID 6568007

• Glycolytic reprogramming underlies immune cell activation by polyethylene wear particles. Biomaterials advances Maduka, C. V., Habeeb, O. M., Kuhnert, M. M., Hakun, M., Goodman, S. B., Contag, C. H. 2023; 152: 213495

  Abstract

  Primary total joint arthroplasties (TJAs) are widely and successfully applied reconstructive procedures to treat end-stage arthritis. Nearly 50% of TJAs are now performed in young patients, posing a new challenge: performing TJAs which last a lifetime. The urgency is justified because subsequent TJAs are costlier and fraught with higher complication rates, not to mention the toll taken on patients and their families. Polyethylene particles, generated by wear at joint articulations, drive aseptic loosening by inciting insidious inflammation associated with surrounding bone loss. Down modulating polyethylene particle-induced inflammation enhances integration of implants to bone (osseointegration), preventing loosening. A promising immunomodulation strategy could leverage immune cell metabolism, however, the role of immunometabolism in polyethylene particle-induced inflammation is unknown. Our findings reveal that immune cells exposed to sterile or contaminated polyethylene particles show fundamentally altered metabolism, resulting in glycolytic reprogramming. Inhibiting glycolysis controlled inflammation, inducing a pro-regenerative phenotype that could enhance osseointegration.

  View details for DOI 10.1016/j.bioadv.2023.213495

  View details for PubMedID 37301057

• Bone regeneration in inflammation with aging and cell-based immunomodulatory therapy. Inflammation and regeneration Kushioka, J., Chow, S. K., Toya, M., Tsubosaka, M., Shen, H., Gao, Q., Li, X., Zhang, N., Goodman, S. B. 2023; 43 (1): 29

  Abstract

  Aging of the global population increases the incidence of osteoporosis and associated fragility fractures, significantly impacting patient quality of life and healthcare costs. The acute inflammatory reaction is essential to initiate healing after injury. However, aging is associated with "inflammaging", referring to the presence of systemic low-level chronic inflammation. Chronic inflammation impairs the initiation of bone regeneration in elderly patients. This review examines current knowledge of the bone regeneration process and potential immunomodulatory therapies to facilitate bone healing in inflammaging.Aged macrophages show increased sensitivity and responsiveness to inflammatory signals. While M1 macrophages are activated during the acute inflammatory response, proper resolution of the inflammatory phase involves repolarizing pro-inflammatory M1 macrophages to an anti-inflammatory M2 phenotype associated with tissue regeneration. In aging, persistent chronic inflammation resulting from the failure of M1 to M2 repolarization leads to increased osteoclast activation and decreased osteoblast formation, thus increasing bone resorption and decreasing bone formation during healing.Inflammaging can impair the ability of stem cells to support bone regeneration and contributes to the decline in bone mass and strength that occurs with aging. Therefore, modulating inflammaging is a promising approach for improving bone health in the aging population. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may benefit bone regeneration in inflammation. Preconditioning MSCs with pro-inflammatory cytokines affects MSCs' secretory profile and osteogenic ability. MSCs cultured under hypoxic conditions show increased proliferation rates and secretion of growth factors. Resolution of inflammation via local delivery of anti-inflammatory cytokines is also a potential therapy for bone regeneration in inflammaging. Scaffolds containing anti-inflammatory cytokines, unaltered MSCs, and genetically modified MSCs can also have therapeutic potential. MSC exosomes can increase the migration of MSCs to the fracture site and enhance osteogenic differentiation and angiogenesis.In conclusion, inflammaging can impair the proper initiation of bone regeneration in the elderly. Modulating inflammaging is a promising approach for improving compromised bone healing in the aging population.

  View details for DOI 10.1186/s41232-023-00279-1

  View details for PubMedID 37231450

  View details for PubMedCentralID 2880220

• Bioenergetic Profile Of Mesenchymal Stromal Cells And Macrophages In The Presence Of An Inflammatory Stimulus In A 3D Model Teissier, V., Gao, Q., Shen, H., Li, J., Li, X., Huang, E., Kushioka, J., Toya, M., Tsubosaka, M., Hirata, H., Alizadeh, H., Maduka, C., Zhang, N., Contag, C., Yang, Y. P., Goodman, S. B. MARY ANN LIEBERT, INC. 2023

  View details for Web of Science ID 001120356800285

• Selecting a High-dose Antibiotic-laden Cement Knee Spacer. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Hollyer, I., Ivanov, D., Kappagoda, S., Lowenberg, D. W., Goodman, S. B., Amanatullah, D. F. 2023

  Abstract

  Periprosthetic infection (PJI) after total knee arthroplasty (TKA) remains a common and challenging problem for joint replacement surgeons and patients. Once the diagnosis of PJI has been made, patient goals and characteristics and the infection timeline dictate treatment. Most commonly, this involves a two-stage procedure with removal of all implants, debridement, and placement of a static or dynamic antibiotic spacer. Static spacers are commonly indicated for older, less healthy patients that would benefit from soft tissue rest after initial debridement. Mobile spacers are typically used in younger, healthier patients to improve quality of life and reduce soft tissue contractures during antibiotic spacer treatment. Spacers are highly customizable with regard to antibiotic choice, cement variety, and spacer design, each with reported advantages, drawbacks, and indications that will be covered in this article. While no spacer has yet to be demonstrated as superior to any other, the modern arthroplasty surgeon must be familiar with the available modalities to optimize treatment for each patient. Here we propose a treatment algorithm to assist surgeons in deciding on treatment for PJI after TKA. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.25570

  View details for PubMedID 37127938

• Sex Differences Of Nf-κB-targeted Therapy For Mitigating Chronic Inflammation In Bone Toya, M., Kushioka, J., Shen, H., Utsunomiya, T., Huang, E., Hirata, H., Tsubosaka, M., Gao, Q., Teissier, V., Li, X., Zhang, N., Goodman, S. B. MARY ANN LIEBERT, INC. 2023

  View details for Web of Science ID 001120356800181

• Arthroplasty for femoral neck fractures is at risk for under restoration of lateral femoral offset. Hip international : the journal of clinical and experimental research on hip pathology and therapy Shah, H. N., Barrett, A. A., Finlay, A. K., Arora, P., Bellino, M. J., Bishop, J. A., Gardner, M. J., Miller, M. D., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2023: 11207000231169914

  Abstract

  PURPOSE: The aim of the study was to determine the restoration of hip biomechanics through lateral offset, leg length, and acetabular component position when comparing non-arthroplasty surgeons (NAS) to elective arthroplasty surgeons (EAS).METHODS: 131 patients, with a femoral neck fracture treated with a THA by 7 EAS and 20 NAS, were retrospectively reviewed. 2 blinded observers measured leg-length discrepancy, femoral offset, and acetabular component position. Multivariate logistic regression models examined the association between the surgeon groups and restoration of lateral femoral, acetabular offset, leg length discrepancy, acetabular anteversion, acetabular position, and component size, while adjusting for surgical approach and spinal pathology.RESULTS: NAS under-restored 4.8mm of lateral femoral offset (43.9±8.7mm) after THA when compared to the uninjured side (48.7±7.1mm, p=0.044). NAS were at risk for under-restoring lateral femoral offset when compared to EAS (p=0.040). There was no association between lateral acetabular offset, leg length, acetabular position, or component size and surgeon type.CONCLUSIONS: Lateral femoral offset is at risk for under-restoration after THA for femoral neck fractures, when performed by surgeons that do not regularly perform elective THA. This indicates that lateral femoral offset is an under-appreciated contributor to hip instability when performing THA for a femoral neck fracture. Lateral femoral offset deserves as much attention and awareness as acetabular component position since a secondary analysis of our data reveal that preoperative templating and intraoperative imaging did not prevent under-restoration.

  View details for DOI 10.1177/11207000231169914

  View details for PubMedID 37128124

• Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model. Stem cell research & therapy Teissier, V., Gao, Q., Shen, H., Li, J., Li, X., Huang, E. E., Kushioka, J., Toya, M., Tsubosaka, M., Hirata, H., Alizadeh, H. V., Maduka, C. V., Contag, C. H., Yang, Y. P., Zhang, N., Goodman, S. B. 2023; 14 (1): 99

  Abstract

  Continuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway.We cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species-ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs.Exposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days.This work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.

  View details for DOI 10.1186/s13287-023-03260-4

  View details for PubMedID 37085909

  View details for PubMedCentralID PMC10122387

• Assessment of Team Dynamics and Operative Efficiency in Hip and Knee Arthroplasty. JAMA surgery Cousins, H. C., Cahan, E. M., Steere, J. T., Maloney, W. J., Goodman, S. B., Miller, M. D., Huddleston, J. I., Amanatullah, D. F. 2023

  Abstract

  Surgical team communication is a critical component of operative efficiency. The factors underlying optimal communication, including team turnover, role composition, and mutual familiarity, remain underinvestigated in the operating room.To assess staff turnover, trainee involvement, and surgeon staff preferences in terms of intraoperative efficiency.Retrospective analysis of staff characteristics and operating times for all total joint arthroplasties was performed at a tertiary academic medical center by 5 surgeons from January 1 to December 31, 2018. Data were analyzed from May 1, 2021, to February 18, 2022. The study included cases with primary total hip arthroplasties (THAs) and primary total knee arthroplasties (TKAs) comprising all primary total joint arthroplasties performed over the 1-year study interval.Intraoperative turnover among nonsurgical staff, presence of trainees, and presence of surgeon-preferred staff.Incision time, procedure time, and room time for each surgery. Multivariable regression analyses between operative duration, presence of surgeon-preferred staff, and turnover among nonsurgical personnel were conducted.A total of 641 cases, including 279 THAs (51% female; median age, 64 [IQR, 56.3-71.5] years) and 362 TKAs (66% [238] female; median age, 68 [IQR, 61.1-74.1] years) were considered. Turnover among circulating nurses was associated with a significant increase in operative duration in both THAs and TKAs, with estimated differences of 19.6 minutes (SE, 3.5; P < .001) of room time in THAs and 14.0 minutes (SE, 3.1; P < .001) of room time in TKAs. The presence of a preferred anesthesiologist or surgical technician was associated with significant decreases of 26.5 minutes (SE, 8.8; P = .003) of procedure time and 12.6 minutes (SE, 4.0; P = .002) of room time, respectively, in TKAs. The presence of a surgeon-preferred vendor was associated with a significant increase in operative duration in both THAs (26.3 minutes; SE, 7.3; P < .001) and TKAs (29.6 minutes; SE, 9.6; P = .002).This study found that turnover among operative staff is associated with procedural inefficiency. In contrast, the presence of surgeon-preferred staff may facilitate intraoperative efficiency. Administrative or technologic support of perioperative communication and team continuity may help improve operative efficiency.

  View details for DOI 10.1001/jamasurg.2023.0168

  View details for PubMedID 36947044

  View details for PubMedCentralID PMC10034665

• Improving Biocompatibility for Next Generation of Metallic Implants. Progress in materials science Bandyopadhyay, A., Mitra, I., Goodman, S. B., Kumar, M., Bose, S. 2023; 133

  Abstract

  The increasing need for joint replacement surgeries, musculoskeletal repairs, and orthodontics worldwide prompts emerging technologies to evolve with healthcare's changing landscape. Metallic orthopaedic materials have a shared application history with the aerospace industry, making them only partly efficient in the biomedical domain. However, suitability of metallic materials in bone tissue replacements and regenerative therapies remains unchallenged due to their superior mechanical properties, eventhough they are not perfectly biocompatible. Therefore, exploring ways to improve biocompatibility is the most critical step toward designing the next generation of metallic biomaterials. This review discusses methods of improving biocompatibility of metals used in biomedical devices using surface modification, bulk modification, and incorporation of biologics. Our investigation spans multiple length scales, from bulk metals to the effect of microporosities, surface nanoarchitecture, and biomolecules such as DNA incorporation for enhanced biological response in metallic materials. We examine recent technologies such as 3D printing in alloy design and storing surface charge on nanoarchitecture surfaces, metal-on-metal, and ceramic-on-metal coatings to present a coherent and comprehensive understanding of the subject. Finally, we consider the advantages and challenges of metallic biomaterials and identify future directions.

  View details for DOI 10.1016/j.pmatsci.2022.101053

  View details for PubMedID 36686623

• Abrieb bei Metall-Metall-Gleitpaarungen : Was haben wir aus den letzten Jahrzehnten gelernt? Orthopadie (Heidelberg, Germany) Knecht, C., Polakof, L., Behrens, J., Goodman, S. B. 2023

  Abstract

  Metal-on-metal (MoM) bearing hip arthroplasty saw increasing utilization and peaked in the 1990s and early 2000s. Although the linear and volumetric wear rate for aMoM bearings was lower than its polyethylene counterpart, metal ion particles were found to be approximately 10 *smaller and 500 *higher in quantity compared to polyethylene wear debris. Research into these articulations have demonstrated their relationship to the formation of lymphocyte-mediated adverse local tissue reactions. The work-up for metal particle-associated conditions (metallosis) includes athorough patient history and physical examination, blood laboratory studies for metal ion concentrations, and advanced imaging studies including magnetic resonance imaging (MRI). The treatment of metallosis and adverse local tissue reactions ranges from close serial observation to extensive debridement and full revision of arthroplasty components, when indicated.

  View details for DOI 10.1007/s00132-023-04346-w

  View details for PubMedID 36820850

• Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss-A Pilot Study. Biomolecules Makarczyk, M. J., Hines, S., Yagi, H., Li, Z. A., Aguglia, A. M., Zbikowski, J., Padget, A. M., Gao, Q., Bunnell, B. A., Goodman, S. B., Lin, H. 2023; 13 (2)

  Abstract

  Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a "synovitis"-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1β (IL-1β), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-κB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-κB ODNs and BMP-7 can be further validated in future clinical studies.

  View details for DOI 10.3390/biom13020384

  View details for PubMedID 36830751

• Complications, Implant Survivorships, and Functional Outcomes of Conversion Total Knee Arthroplasty with Prior Hardware. The Journal of arthroplasty Apinyankul, R., Hui, A. Y., Hwang, K., Segovia, N. A., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2023

  Abstract

  End-stage knee osteoarthritis with retained peri-articular hardware is a frequent scenario. Conversion total knee arthroplasty (TKA) leads to excellent outcomes, but poses unique challenges. The evidence supporting retention vs. removal of hardware during TKA is controversial.Patients who underwent TKA with prior hardware between January 2009 and December 2019 were identified. A total of 148 patients underwent TKA with prior hardware. Mean follow-up was 60 months (range, 24 to 223). Univariate and multivariable analyses were used to study correlations among factors and surgical-related complications, prosthesis failures, and functional outcomes.The complication rate was 28 of 148 (18.9%). The use of a quadriceps snips in addition to a medial parapatellar arthrotomy was associated with a higher complication (Odds ratio (OR) 20.7, p < 0.05), implant failures (OR 13.9, p < 0.05), and lower Veteran Rand 12 Mental Score (VR-12 MS) (-14.8, p < 0.05). Hardware removal vs. retention and use of single vs. multiple incisions were not associated with complications or prosthesis failures. Removal of all hardware was associated with significantly higher (+7.3, p < 0.05) VR-12 MS compared to retention of all hardware.TKA with prior hardware was associated with more complications, implant failures, and lower VR-12 MS when a more constrained construct or quadriceps snip was performed. This probably reflects the level of difficulty of the procedure, rather than the surgical approach used. Hardware removal or retention was not associated with complications or implant failures; however, removal rather than retention of all prior hardware is associated with increased general health outcomes.

  View details for DOI 10.1016/j.arth.2023.01.049

  View details for PubMedID 36758842

• Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs. Journal of visualized experiments : JoVE Makarcyzk, M. J., Li, Z. A., Yu, I., Yagi, H., Zhang, X., Yocum, L., Li, E., Fritch, M. R., Gao, Q., Bunnell, B. A., Goodman, S. B., Tuan, R. S., Alexander, P. G., Lin, H. 2023

  Abstract

  The high prevalence of debilitating joint diseases like osteoarthritis (OA) poses a high socioeconomic burden. Currently, the available drugs that target joint disorders are mostly palliative. The unmet need for effective disease-modifying OA drugs (DMOADs) has been primarily caused by the absence of appropriate models for studying the disease mechanisms and testing potential DMOADs. Herein, we describe the establishment of a miniature synovial joint-mimicking microphysiological system (miniJoint) comprising adipose, fibrous, and osteochondral tissue components derived from human mesenchymal stem cells (MSCs). To obtain the three-dimensional (3D) microtissues, MSCs were encapsulated in photocrosslinkable methacrylated gelatin before or following differentiation. The cell-laden tissue constructs were then integrated into a 3D-printed bioreactor, forming the miniJoint. Separate flows of osteogenic, fibrogenic, and adipogenic media were introduced to maintain the respective tissue phenotypes. A commonly shared stream was perfused through the cartilage, synovial, and adipose tissues to enable tissue crosstalk. This flow pattern allows the induction of perturbations in one or more of the tissue components for mechanistic studies. Furthermore, potential DMOADs can be tested via either "systemic administration" through all the medium streams or "intraarticular administration" by adding the drugs to only the shared "synovial fluid"-simulating flow. Thus, the miniJoint can serve as a versatile in vitro platform for efficiently studying disease mechanisms and testing drugs in personalized medicine.

  View details for DOI 10.3791/64186

  View details for PubMedID 36779602

• Stereochemistry Determines Immune Cellular Responses to Polylactide Implants. ACS biomaterials science & engineering Maduka, C. V., Alhaj, M., Ural, E., Kuhnert, M. M., Habeeb, O. M., Schilmiller, A. L., Hankenson, K. D., Goodman, S. B., Narayan, R., Contag, C. H. 2023

  Abstract

  Repeating l- and d-chiral configurations determine polylactide (PLA) stereochemistry, which affects its thermal and physicochemical properties, including degradation profiles. Clinically, degradation of implanted PLA biomaterials promotes prolonged inflammation and excessive fibrosis, but the role of PLA stereochemistry is unclear. Additionally, although PLA of varied stereochemistries causes differential immune responses in vivo, this observation has yet to be effectively modeled in vitro. A bioenergetic model was applied to study immune cellular responses to PLA containing >99% l-lactide (PLLA), >99% d-lactide (PDLA), and a 50/50 melt-blend of PLLA and PDLA (stereocomplex PLA). Stereocomplex PLA breakdown products increased IL-1β, TNF-α, and IL-6 protein levels but not MCP-1. Expression of these proinflammatory cytokines is mechanistically driven by increases in glycolysis in primary macrophages. In contrast, PLLA and PDLA degradation products selectively increase MCP-1 protein expression. Although both oxidative phosphorylation and glycolysis are increased with PDLA, only oxidative phosphorylation is increased with PLLA. For each biomaterial, glycolytic inhibition reduces proinflammatory cytokines and markedly increases anti-inflammatory (IL-10) protein levels; differential metabolic changes in fibroblasts were observed. These findings provide mechanistic explanations for the diverse immune responses to PLA of different stereochemistries and underscore the pivotal role of immunometabolism in the biocompatibility of biomaterials applied in medicine.

  View details for DOI 10.1021/acsbiomaterials.2c01279

  View details for PubMedID 36634351

• The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid-induced osteonecrosis of the femoral head in rabbits. Journal of biomedical materials research. Part A Tsubosaka, M., Maruyama, M., Lui, E., Moeinzadeh, S., Huang, E. E., Kushioka, J., Hirata, H., Jain, C., Storaci, H. W., Chan, C., Toya, M., Gao, Q., Teissier, V., Shen, H., Li, X., Zhang, N., Matsumoto, T., Kuroda, R., Goodman, S. B., Yang, Y. P. 2023

  Abstract

  Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of beta-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS+PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

  View details for DOI 10.1002/jbm.a.37495

  View details for PubMedID 36606330

• MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects. Theranostics Suryadevara, V., Hajipour, M. J., Adams, L. C., Aissaoui, N. M., Rashidi, A., Kiru, L., Theruvath, A. J., Huang, C., Maruyama, M., Tsubosaka, M., Lyons, J. K., Wu, W. E., Roudi, R., Goodman, S. B., Daldrup-Link, H. E. 2023; 13 (8): 2710-2720

  Abstract

  Rationale: Efficient labeling methods for mesenchymal stem cells (MSCs) are crucial for tracking and understanding their behavior in regenerative medicine applications, particularly in cartilage defects. MegaPro nanoparticles have emerged as a potential alternative to ferumoxytol nanoparticles for this purpose. Methods: In this study, we employed mechanoporation to develop an efficient labeling method for MSCs using MegaPro nanoparticles and compared their effectiveness with ferumoxytol nanoparticles in tracking MSCs and chondrogenic pellets. Pig MSCs were labeled with both nanoparticles using a custom-made microfluidic device, and their characteristics were analyzed using various imaging and spectroscopy techniques. The viability and differentiation capacity of labeled MSCs were also assessed. Labeled MSCs and chondrogenic pellets were implanted into pig knee joints and monitored using MRI and histological analysis. Results: MegaPro-labeled MSCs demonstrated shorter T2 relaxation times, higher iron content, and greater nanoparticle uptake compared to ferumoxytol-labeled MSCs, without significantly affecting their viability and differentiation capacity. Post-implantation, MegaPro-labeled MSCs and chondrogenic pellets displayed a strong hypointense signal on MRI with considerably shorter T2* relaxation times compared to adjacent cartilage. The hypointense signal of both MegaPro- and ferumoxytol-labeled chondrogenic pellets decreased over time. Histological evaluations showed regenerated defect areas and proteoglycan formation with no significant differences between the labeled groups. Conclusion: Our study demonstrates that mechanoporation with MegaPro nanoparticles enables efficient MSC labeling without affecting viability or differentiation. MegaPro-labeled cells show enhanced MRI tracking compared to ferumoxytol-labeled cells, emphasizing their potential in clinical stem cell therapies for cartilage defects.

  View details for DOI 10.7150/thno.82620

  View details for PubMedID 37215574

• Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence? Current osteoporosis reports Lopas, L. A., Shen, H., Zhang, N., Jang, Y., Tawfik, V. L., Goodman, S. B., Natoli, R. M. 2022

  Abstract

  PURPOSE OF REVIEW: The purpose of this review is to summarize the clinical and basic science methods used to assess fracture healing and propose a framework to improve the translational possibilities.RECENT FINDINGS: Mainstays of fracture healing assessment include clinical examination, various imaging modalities, and assessment of function. Pre-clinical studies have yielded insight into biomechanical progression as well as the genetic, molecular, and cellular processes of fracture healing. Efforts are emerging to identify early markers to predict impaired healing and possibly early intervention to alter these processes. Despite of the differences in clinical and preclinical research, opportunities exist to unify and improve the translational efforts between these arenas to develop and optimize our ability to assess and predict fracture healing, thereby improving the clinical care of these patients.

  View details for DOI 10.1007/s11914-022-00770-7

  View details for PubMedID 36534307

• Revision hip arthroplasty using a modular, cementless femoral stem: long-term follow-up. The Journal of arthroplasty Valtanen, R. S., Hwang, K. L., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2022

  Abstract

  BACKGROUND: As the number of primary total hip arthroplasty (THA) cases increase, so does the demand for revision operations. However, long-term follow-up data for revision THA is lacking.METHODS: A retrospective review was completed of patients who underwent revision THA at a single institution between January 2002 and October 2007 using a cementless modular stem. Patient demographic, clinical, and radiographic data was collected. Preoperative and postoperative patient reported outcome (PRO) scores were compared at a minimum of fourteen-year follow-up.RESULTS: Eighty-four patients (89 hips) with a median age of 69 years (range, 28 to 88) at operation were included. Indications for revision included aseptic loosening (84.2%), infection (12.4%), and periprosthetic fracture (3.4%). Twenty-two hips sustained at least one complication: intraoperative fracture (7.9%), dislocation (6.7%), prosthetic joint infection (4.5%), deep venous thrombosis (3.4%), late periprosthetic fracture (2.2%). There were no modular junction complications. Eight patients underwent reoperations; only three involved the stem. Thirty-eight patients (45%) were deceased prior to final follow-up without known reoperations. Twenty-seven patients (32%) were lost to follow-up. Twenty-one patients (23%) were alive at minimum fourteen-year follow-up. Complete PROs were available for nineteen patients (range, 14 to 18.5 years follow-up). Significant improvement was seen in UCLA Activity, VR-12 physical, HOOS, JR., and HHS pain and function scores.CONCLUSION: Challenges of long-term follow-up include patient migration, an unwillingness to travel for re-examination, medical comorbidities, advanced age, and death. The cementless modular revision stem demonstrated long-term clinical success and remains a safe and reliable option for complex revision operations.

  View details for DOI 10.1016/j.arth.2022.12.018

  View details for PubMedID 36535440

• Experimental models to study osteoarthritis pain and develop therapeutics. Osteoarthritis and cartilage open Riewruja, K., Makarczyk, M., Alexander, P. G., Gao, Q., Goodman, S. B., Bunnell, B. A., Gold, M. S., Lin, H. 2022; 4 (4): 100306

  Abstract

  Pain is the predominant symptom of osteoarthritis (OA) that drives patients to seek medical care. Currently, there are no pharmacological treatments that can reverse or halt the progression of OA. Safe and efficacious medications for long-term management of OA pain are also unavailable. Understanding the mechanisms behind OA pain generation at onset and over time is critical for developing effective treatments. In this narrative review, we first summarize our current knowledge on the innervation of the knee joint, and then discuss the molecular mechanism(s) currently thought to underlie OA pain. In particular, we focus on the contribution of each joint component to the generation of pain. Next, the current experimental models for studying OA pain are summarized, and the methods to assess pain in rodents are presented. The potential application of emerging microphysiological systems in OA pain research is especially highlighted. Lastly, we discuss the current challenge in standardizing models and the selection of appropriate systems to address specific questions.

  View details for DOI 10.1016/j.ocarto.2022.100306

  View details for PubMedID 36474784

• The Environmental Impact of Orthopaedic Surgery. The Journal of bone and joint surgery. American volume Saleh, J. R., Mitchell, A., Kha, S. T., Outterson, R., Choi, A., Allen, L., Chang, T., Ladd, A. L., Goodman, S. B., Fox, P., Chou, L. 2022

  Abstract

  ➤: There are a growing number of opportunities within the field of orthopaedic surgery to address climate change and investigate ways to promote sustainability.➤: Orthopaedic surgeons can take a proactive role in addressing climate change and its impacts within the areas of operating-room waste, carbon emissions from transportation and implant manufacturing, anesthetic gases, and water usage.➤: Future studies are needed to further these initiatives on quantifying and decreasing environmental impact and furthering sustainable use of our resources.

  View details for DOI 10.2106/JBJS.22.00548

  View details for PubMedID 36574633

• Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration. Nature communications Andrew, T. W., Koepke, L. S., Wang, Y., Lopez, M., Steininger, H., Struck, D., Boyko, T., Ambrosi, T. H., Tong, X., Sun, Y., Gulati, G. S., Murphy, M. P., Marecic, O., Telvin, R., Schallmoser, K., Strunk, D., Seita, J., Goodman, S. B., Yang, F., Longaker, M. T., Yang, G. P., Chan, C. K. 2022; 13 (1): 6491

  Abstract

  Sexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice. We found that skeletal stem cell (SSC) mediated regeneration in female mice is dependent on estrogen signaling but SSCs from male mice do not exhibit similar estrogen responsiveness. Mechanistically, we found that estrogen acts directly on the SSC lineage in mice and humans by up-regulating multiple skeletogenic pathways and is necessary for the stem cell's ability to self- renew and differentiate. Our results also suggest a clinically applicable strategy to accelerate bone healing using localized estrogen hormone therapy.

  View details for DOI 10.1038/s41467-022-34063-5

  View details for PubMedID 36310174

• Outcome of the Wagner Cone femoral component for difficult anatomical conditions during total hip arthroplasty. International orthopaedics Lawson, K., Hwang, K. L., Montgomery, S., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2022

  Abstract

  PURPOSE: Total hip arthroplasty (THA) in patients with small or unusual proximal femoral anatomy is challenging due to sizing issues, control of version, and implant fixation. The Wagner Cone is a monoblock, fluted, tapered stem with successful outcomes for these patients; however, there is limited information on subsidence, a common finding with cementless stems.METHODS: We retrospectively reviewed our cases using the modified Wagner Cone (Zimmer, Warsaw, IN) implanted over a 13-year period (2006-2019) in patients with small or abnormal proximal femoral anatomy. We performed 144 primary THAs in 114 patients using this prosthesis. Mean follow-up was 4.5±3.4years (range, 1-13years). Common reasons for implantation were hip dysplasia (52%) and osteoarthritis in patients with small femoral proportions (22%). Analysis of outcomes included assessment of stem subsidence and stability.RESULTS: Survival was 98.6% in aseptic cases; revision-free survival was 97.9%. Femoral subsidence occurred in 84 cases (58%). No subsidence progressed after 3months. Of those that subsided, the mean distance was 2.8±2.0mm. There was less subsidence in stems that stabilized prior to sixweeks (2.2±1.4mm) compared to those that continued until 12weeks (3.9±1.6, p=0.02). Harris Hip, UCLA, and WOMAC scores significantly improved from pre-operative evaluation (p<0.001*, p<0.003*, p≪0.001*); there was no difference in outcome between patients with and without subsidence (p=0.430, p=0.228, p=0.147).CONCLUSION: The modified Wagner Cone demonstrates excellent clinical outcomes in patients with challenging proximal femoral anatomy. Subsidence is minor, stops by 3months, and does not compromise clinical outcome.

  View details for DOI 10.1007/s00264-022-05608-6

  View details for PubMedID 36224431

• Relationship of Aging, Inflammation, and Skeletal Stem Cells and Their Effects on Fracture Repair. Current osteoporosis reports Goodnough, L. H., Goodman, S. B. 2022

  Abstract

  PURPOSE OF REVIEW: This review summarizes recent investigations into the cellular and molecular effects of skeletal aging on the inflammatory response and stem cell function after fracture.RECENT FINDINGS: Proper regulation of the inflammatory phase of fracture healing is essential. Aging is associated with chronic inflammation, which inhibits bone formation and promotes bone resorption. Osteogenic differentiation and anti-senescence pathways in skeletal stem cells are impaired in geriatric fractures. As the population ages, fragility fractures will continue to represent a significant clinical problem, which will require innovative clinical solutions. Skeletal stem cells in geriatric individuals demonstrate defects in anti-senescence pathways that lead to impaired osteogenic differentiation in vitro in humans. Small molecule-based therapies can partially reverse the aging phenotype. In the future, molecular- or cell-based therapies modulating either inflammatory cells or skeletal stem cells represent potential therapeutic targets to augment contemporary fracture healing interventions in osteoporotic or aging individuals.

  View details for DOI 10.1007/s11914-022-00742-x

  View details for PubMedID 36129609

• Isolated Versus Full Component Revision In Total Knee Arthroplasty For Aseptic Loosening. The Journal of arthroplasty Apinyankul, R., Hwang, K., Segovia, N. A., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2022

  Abstract

  Revision of both femoral and tibial components of a total knee arthroplasty (TKA) for aseptic loosening has favorable outcomes. Revision of only one loose component with retention of others has shorter operative time and lower cost, however, implant survivorship and clinical outcomes of these different operations are unclear.Between January 2009 and December 2019, a consecutive cohort of revision TKA were reviewed. Univariate and multivariable analyses were used to study correlations among factors and surgical related complications, time to prosthesis failure, and functional outcomes (University of California Los Angeles (UCLA), Knee Society (KS) functional, Knee osteoarthritis and outcome score for joint replacement (KOOS JR), Veterans RAND 12 (VR-12) physical, and VR-12 mental).A total of 238 patients underwent revision TKA for aseptic loosening. The mean follow-up time was 61 months (range 25 to 152). Ten of the 105 patients (9.5%) who underwent full revision (both femoral and tibial components) and 18 of the 133 (13.5%) who underwent isolated revision had subsequent prosthesis failure [Hazard ratio (HR) 0.67, p = 0.343]. The factor analysis of type of revision (full or isolated revision) did not demonstrate a significant difference between groups in terms of complications, implant failures, and times to failure. Metallosis was related to early time to failure [HR 10.11, p < 0.001] and iliotibial band release was associated with more complications (Odds ratio (OR) 9.87, p = 0.027). Preoperative symptoms of instability were associated with the worst improvement in UCLA score. Higher American Society of Anesthesiologists (ASA) and higher Charlson Comorbidity Index (CCI) were related with worse VR-12 physical (-30.5, p = 0.008) and KOOS JR (-4.2, p = 0.050) scores, respectively.Isolated and full component revision TKA for aseptic loosening do not differ with respect to prosthesis failures, complications, and clinical results at 5 years. Poor ASA status, increased comorbidities, instability, and a severe bone defect are related to worse functional improvement.

  View details for DOI 10.1016/j.arth.2022.09.006

  View details for PubMedID 36099937

• The Impact of Extended Trochanteric Osteotomy with Cerclage Fixation in Revision Total Hip Arthroplasty for Prosthetic Joint Infection. The Journal of arthroplasty Whittaker, M. J., Arora, P., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2022

  Abstract

  BACKGROUND: An extended trochanteric osteotomy (ETO) is a powerful tool for femoral component revision. There is limited evidence that directly supports its use in the setting of a prosthetic joint infection (PJI). Cerclage fixation raises the theoretical concern for persistent infection.METHODS: The institutional database included 76 ETOs for revision arthroplasty between January 1, 2008 and December 31, 2019. The cohort was divided based on indication for femoral component revision: PJI versus aseptic revision. The PJI group was subdivided based on second stage exchange versus retention of initial cerclage fixation. Operative time, estimated blood loss, complications, and rate of repeat revision surgery were evaluated.RESULTS: Forty-nine patients (64%) underwent revision for PJI and 27 patients (36%) underwent aseptic revision. There was no significant difference in operative times (p = 0.082), postoperative complications (p = 0.258), or rate of repeat revision surgery (p = 0.322) between groups. Of the 49 patients in the PJI group, 40 (82%) retained cerclage fixation while 9 (18%) had cerclage exchange. Cerclage exchange did not significantly impact operative time (p = 0.758), blood loss (p = 0.498), rate of repeat revision surgery (p = 0.302), or postoperative complications (p = 0.253) including infection (p = 0.639).CONCLUSION: An ETO remains a powerful tool for femoral component removal, even in the presence of a PJI. A multi-institutional investigation would be required to validate observed trends toward better infection control with cerclage exchange. Cerclage exchange did not appear to increase operative time, blood loss, or postoperative complication rates.

  View details for DOI 10.1016/j.arth.2022.08.041

  View details for PubMedID 36067886

• Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect. Journal of orthopaedic translation Huang, E. E., Zhang, N., Ganio, E. A., Shen, H., Li, X., Ueno, M., Utsunomiya, T., Maruyama, M., Gao, Q., Su, N., Yao, Z., Yang, F., Gaudilliere, B., Goodman, S. B. 2022; 36: 64-74

  Abstract

  Background: A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous bone graft is often insufficient in quantity or quality for transplantation to these large defects. Recently, tissue engineering methods using mesenchymal stem cells (MSCs) have been proposed as an alternative treatment. However, the underlying biological principles and optimal techniques for tissue regeneration of bone using stem cell therapy have not been completely elucidated.Methods: In this study, we compare the early cellular dynamics of healing between bone graft transplantation and MSC therapy in a murine chronic femoral critical-size bone defect. We employ high-dimensional mass cytometry to provide a comprehensive view of the differences in cell composition, stem cell functionality, and immunomodulatory activity between these two treatment methods one week after transplantation.Results: We reveal distinct cell compositions among tissues from bone defect sites compared with original bone graft, show active recruitment of MSCs to the bone defect sites, and demonstrate the phenotypic diversity of macrophages and T cells in each group that may affect the clinical outcome.Conclusion: Our results provide critical data and future directions on the use of MSCs for treating critical size defects to regenerate bone.Translational Potential of this article: This study showed systematic comparisons of the cellular and immunomodulatory profiles among different interventions to improve the healing of the critical-size bone defect. The results provided potential strategies for designing robust therapeutic interventions for the unmet clinical need of treating critical-size bone defects.

  View details for DOI 10.1016/j.jot.2022.05.010

  View details for PubMedID 35979174

• A Physician Assistant Is Associated With Higher Patient Satisfaction With Outpatient Orthopedic Surgery ORTHOPEDICS Korth, M., Lu, L. Y., Finlay, A. K., Kamal, R. N., Goodman, S. B., Maloney, W. J., Amanatullah, D. F., Huddleston, J. I. 2022; 45 (5): E252-E256

  Abstract

  Patient satisfaction is increasingly used to assess the quality of care and determine physician reimbursement. Patient characteristics influence patient satisfaction, but the effect of physician practice parameters on satisfaction has not been studied in detail. Outpatient satisfaction scores from 11,059 patients who rated 24 orthopedic surgeons from a single institution were studied. Practice-related parameters were collected in a provider-reported survey. Univariate logistic regressions were used to test the associations between each provider characteristic and the likelihood of receiving a 5-star rating on a selection of 16 Press Ganey patient satisfaction questions. The presence of a physician assistant in the clinic positively affected the 5-star rating for all but 1 of the patient satisfaction questions examined, including overall satisfaction (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P=.031); the likelihood of being recommended to others (OR, 1.57; 95% CI, 1.16-2.14; P=.004); and friendliness/courtesy (OR, 1.58; 95% CI, 1.17-2.13; P=.003). However, having a fellow or nurse practitioner in the clinic, treating children, productivity (measured as total relative value units), taking trauma call, and provider distance from home were not associated with higher scores for any of the Press Ganey patient satisfaction questions. Having a physician assistant in the clinic is an actionable, practice-specific characteristic that positively affects patient satisfaction on many levels and may ultimately improve the perception of care. [Orthopedics. 2022;45(5):e252-e256.].

  View details for DOI 10.3928/01477447-20220511-04

  View details for Web of Science ID 001124810800004

  View details for PubMedID 35576483

• Therapeutic effects of MSCs, genetically modified MSCs, and NFkB-inhibitor on chronic inflammatory osteolysis in aged mice. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Kushioka, J., Toya, M., Shen, H., Hirata, H., Zhang, N., Huang, E., Tsubosaka, M., Gao, Q., Teissier, V., Li, X., Utsunomiya, T., Goodman, S. B. 2022

  Abstract

  The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-kB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-kB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15-17-month-old) for six weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared to the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.25434

  View details for PubMedID 36031590

• Synovial joint-on-a-chip for modeling arthritis: progress, pitfalls, and potential. Trends in biotechnology Li, Z. A., Sant, S., Cho, S. K., Goodman, S. B., Bunnell, B. A., Tuan, R. S., Gold, M. S., Lin, H. 2022

  Abstract

  Disorders of the synovial joint, such as osteoarthritis (OA) and rheumatoid arthritis (RA), afflict a substantial proportion of the global population. However, current clinical management has not been focused on fully restoring the native function of joints. Organ-on-chip (OoC), also called a microphysiological system, which typically accommodates multiple human cell-derived tissues/organs under physiological culture conditions, is an emerging platform that potentially overcomes the limitations of current models in developing therapeutics. Herein, we review major steps in the generation of OoCs for studying arthritis, discuss the challenges faced when these novel platforms enter the next phase of development and application, and present the potential for OoC technology to investigate the pathogenesis of joint diseases and the development of efficacious therapies.

  View details for DOI 10.1016/j.tibtech.2022.07.011

  View details for PubMedID 35995600

• Facilitation Of Bone Defect Healing By IL-4 Over- expressing MSCs Goodman, S. B., Zhang, N., Ueno, M., Yang, F. MARY ANN LIEBERT, INC. 2022: 80-81

  View details for Web of Science ID 000848131900086

• Aberrant Expression of COX-2 and FOXG1 in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors. Cells O'Donnell, B. T., Monjure, T. A., Al-Ghadban, S., Ives, C. J., L'Ecuyer, M. P., Rhee, C., Romero-Lopez, M., Li, Z., Goodman, S. B., Lin, H., Tuan, R. S., Bunnell, B. A. 2022; 11 (15)

  Abstract

  Osteoarthritis (OA) is a degenerative joint disease resulting in limited mobility and severe disability. Type II diabetes mellitus (T2D) is a weight-independent risk factor for OA, but a link between the two diseases has not been elucidated. Adipose stem cells (ASCs) isolated from the infrapatellar fat pad (IPFP) may be a viable regenerative cell for OA treatment. This study analyzed the expression profiles of inflammatory and adipokine-related genes in IPFP-ASCs of non-diabetic (Non-T2D), pre-diabetic (Pre-T2D), and T2D donors. Pre-T2D ASCs exhibited a substantial decrease in levels of mesenchymal markers CD90 and CD105 with no change in adipogenic differentiation compared to Non-T2D and T2D IPFP-ASCs. In addition, Cyclooxygenase-2 (COX-2), Forkhead box G1 (FOXG1) expression and prostaglandin E2 (PGE2) secretion were significantly increased in Pre-T2D IPFP-ASCs upon stimulation by interleukin-1 beta (IL-1β). Interestingly, M1 macrophages exhibited a significant reduction in expression of pro-inflammatory markers TNFα and IL-6 when co-cultured with Pre-T2D IPFP-ASCs. These data suggest that the heightened systemic inflammation associated with untreated T2D may prime the IPFP-ASCs to exhibit enhanced anti-inflammatory characteristics via suppressing the IL-6/COX-2 signaling pathway. In addition, the elevated production of PGE2 by the Pre-T2D IPFP-ASCs may also suggest the contribution of pre-diabetic conditions to the onset and progression of OA.

  View details for DOI 10.3390/cells11152367

  View details for PubMedID 35954211

• Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial (vol 153, pg 303, 2018) JAMA SURGERY Hah, J., Mackey, S. C., Schmidt, P. 2022; 157 (6): 553

  View details for DOI 10.1001/jamasurg.2022.1392

  View details for Web of Science ID 000809213600033

• Efficacy of Periarticular Multimodal Analgesic Injection Containing High-Dose Ketorolac versus Triamcinolone in Early Postoperative Total Knee Arthroplasty: A Randomized Controlled Trial SURGICAL TECHNOLOGY INTERNATIONAL-INTERNATIONAL DEVELOPMENTS IN SURGERY AND SURGICAL RESEARCH Apinyankul, R., Lilakhunakon, K., Vechvitvarakul, M., Witayakom, W., Goodman, S. B. 2022; 40

  View details for Web of Science ID 001001091900007

• Efficacy of Periarticular Multimodal Analgesic Injection Containing High-Dose Ketorolac versus Triamcinolone in Early Postoperative Total Knee Arthroplasty: A Randomized Controlled Trial. Surgical technology international Apinyankul, R., Lilakhunakon, K., Witayakom, W., Vechvitvarakul, M., Goodman, S. B. 2022; 40

  Abstract

  INTRODUCTION: Periarticular multimodal analgesic injection associates with less postoperative (post-op) pain after total knee arthroplasty (TKA) with less opioid consumption. The combination of additives and dosage are various and controversial. Evidence of ketorolac compared to triamcinolone as an additive is limited in terms of efficacy and safety.MATERIALS AND METHODS: Fifty-six patients with unilateral TKA were randomized to receive either 60mg ketorolac or 80mg triamcinolone acetonide as cocktail additives in periarticular injection. Significant threshold was considered if the adjusted mean difference of morphine consumption was greater than 3mg at any timepoint. The primary outcomes were morphine consumptions at immediate post-op, 24 hour (h), 48h, and 72h post-op. Pain visual analogue scale (VAS), knee range of motion, straight leg raising ability, and adverse events were secondary outcomes.RESULTS: Adjusted mean differences (ketorolac-triamcinolone) in morphine consumption were -0.4, 2.5, 2.6, and 2.3mg at given timepoints without significance. No difference observed in pain VAS at rest and during motion, post-op knee extension, and straight leg raising ability. However, post-op knee flexion was significantly higher in triamcinolone group at any timepoints (mean differences 10.3, 10.6, and 9.7, respectively, p<0.05).CONCLUSIONS: Periarticular analgesic injection containing 60mg ketorolac provided similar analgesic efficacy and early functional recovery compared with 80mg triamcinolone acetonide. However, triamcinolone may benefit over ketorolac in early post-op knee flexion.

  View details for PubMedID 35453173

• Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial (vol 153, pg 303, 2018) JAMA SURGERY Hah, J., Mackey, S. C., Schmidt, P. 2022

  View details for DOI 10.1001/jamasurg.2017.4915

  View details for Web of Science ID 000784959200002

• Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Li, Z., Lin, Z., Liu, S., Yagi, H., Zhang, X., Yocum, L., Romero-Lopez, M., Rhee, C., Makarcyzk, M. J., Yu, I., Li, E. N., Fritch, M. R., Gao, Q., Goh, K. B., O'Donnell, B., Hao, T., Alexander, P. G., Mahadik, B., Fisher, J. P., Goodman, S. B., Bunnell, B. A., Tuan, R. S., Lin, H. 2022: e2105909

  Abstract

  Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell-derived microphysiologica system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell-derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial-like fibrous tissue, and adipose tissue are integrated into a microfluidics-enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin-1beta mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the "therapeutic effect" of the nonsteroidal anti-inflammatory drug, naproxen, as well as four other potential disease-modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions.

  View details for DOI 10.1002/advs.202105909

  View details for PubMedID 35436042

• A Review of Biomimetic Topographies and Their Role in Promoting Bone Formation and Osseointegration: Implications for Clinical Use. Biomimetics (Basel, Switzerland) Berger, M. B., Slosar, P., Schwartz, Z., Cohen, D. J., Goodman, S. B., Anderson, P. A., Boyan, B. D. 2022; 7 (2)

  Abstract

  The use of metallic and polymeric materials for implants has been increasing over the past decade. This trend can be attributed to a variety of factors including a significant increase in basic science research focused on implant material characteristics and how various surface modifications may stimulate osseointegration and, ultimately, fusion. There are many interbody fusion devices and dental implants commercially available; however, detailed information about their surface properties, and the effects that various materials and surface modifications may have on osteogenesis, is lacking in the literature. While the concept of bone-implant osseointegration is a relatively recent addition to the spine fusion literature, there is a comparatively large body of literature related to dental implants. The purpose of this article is to summarize the science of surface modified bone-facing implants, focusing on biomimetic material chemistry and topography of titanium implants, to promote a better understanding of how these characteristics may impact bone formation and osseointegration. This manuscript has the following aspects: highlights the role of titanium and its alloys as potent osteoconductive bioactive materials; explores the importance of biomimetic surface topography at the macro-, micro- and nano-scale; summarizes how material surface design can influence osteogenesis and immune responses in vitro; focuses on the kinds of surface modifications that play a role in the process. Biomimetic surface modifications can be varied across many clinically available biomaterials, and the literature supports the hypothesis that those biomaterial surfaces that exhibit physical properties of bone resorption pits, such as roughness and complex hierarchical structures at the submicron and nanoscale, are more effective in supporting osteoblast differentiation in vitro and osteogenesis in vivo.

  View details for DOI 10.3390/biomimetics7020046

  View details for PubMedID 35466263

• Novel Techniques and Future Perspective for Investigating Critical-Size Bone Defects. Bioengineering (Basel, Switzerland) Huang, E. E., Zhang, N., Shen, H., Li, X., Maruyama, M., Utsunomiya, T., Gao, Q., Guzman, R. A., Goodman, S. B. 2022; 9 (4)

  Abstract

  A critical-size bone defect is a challenging clinical problem in which a gap between bone ends will not heal and will become a nonunion. The current treatment is to harvest and transplant an autologous bone graft to facilitate bone bridging. To develop less invasive but equally effective treatment options, one needs to first have a comprehensive understanding of the bone healing process. Therefore, it is imperative to leverage the most advanced technologies to elucidate the fundamental concepts of the bone healing process and develop innovative therapeutic strategies to bridge the nonunion gap. In this review, we first discuss the current animal models to study critical-size bone defects. Then, we focus on four novel analytic techniques and discuss their strengths and limitations. These four technologies are mass cytometry (CyTOF) for enhanced cellular analysis, imaging mass cytometry (IMC) for enhanced tissue special imaging, single-cell RNA sequencing (scRNA-seq) for detailed transcriptome analysis, and Luminex assays for comprehensive protein secretome analysis. With this new understanding of the healing of critical-size bone defects, novel methods of diagnosis and treatment will emerge.

  View details for DOI 10.3390/bioengineering9040171

  View details for PubMedID 35447731

• EFFICACY OF PRECONDITIONED OR GENETICALLY MODIFIED IL4-SECRETING MESENCHYMAL STROMAL CELLS IN A MODEL OF STEROID-ASSOCIATED OSTEONECROSIS OF THE FEMORAL HEAD IN RABBITS Goodman, S., Maruyama, M., Moeinzadeh, S., Guzman, R., Takagi, M., Yang, Y. MARY ANN LIEBERT, INC. 2022: S30

  View details for Web of Science ID 000821187300099

• AN INNERVATED SYNOVIUM-CARTILAGE CHIP FOR MODELING JOINT INFLAMMATION AND ASSOCIATED PAIN Li, Z., Makarcyzk, M. J., Moy, J. K., Yu, I., Liu, F., Gao, Q., Cho, S., Weber, D. J., Bunnell, B. A., Goodman, S. B., Gold, M. S., Lin, H. MARY ANN LIEBERT, INC. 2022: S505

  View details for Web of Science ID 000821187302237

• Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix. International journal of molecular sciences Culla, A. C., Vater, C., Tian, X., Bolte, J., Ahlfeld, T., Bretschneider, H., Pape, A., Goodman, S. B., Gelinsky, M., Zwingenberger, S. 2022; 23 (6)

  Abstract

  To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing.

  View details for DOI 10.3390/ijms23063400

  View details for PubMedID 35328820

• Ageing attenuates bone healing by mesenchymal stem cellsin a microribbon hydrogelwith a murine long bone critical-size defect model. Immunity & ageing : I & A Hirata, H., Zhang, N., Ueno, M., Barati, D., Kushioka, J., Shen, H., Tsubosaka, M., Toya, M., Lin, T., Huang, E., Yao, Z., Wu, J. Y., Zwingenberger, S., Yang, F., Goodman, S. B. 2022; 19 (1): 14

  Abstract

  BACKGROUND: Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice.METHODS: A 2mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (RB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc+MSCs, and Sc+IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (CT), histochemical and immunohistochemical analyses were performed.RESULTS: CT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc+MSCs and Sc+IL4-MSC groups. However, no bridging of bone was observed in all groups. H&E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc+IL4-MSC group. The Sc+IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio.DISCUSSION: IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the RB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.

  View details for DOI 10.1186/s12979-022-00272-1

  View details for PubMedID 35279175

• The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head-CT Based Study. The Journal of arthroplasty Koo, K., Mont, M. A., Cui, Q., Hines, J., Yoon, B., Novicoff, W., Lee, Y. J., Cheng, E. Y., Drescher, W., Hernigou, P., Kim, S., Sugano, N., Zhao, D., Ha, Y., Goodman, S. B., Sakai, T., Jones, L. C., Lee, M. S., Yamamoto, T., Lee, Y., Kang, Y., Burgess, J., Chen, D., Quinlan, N., Xu, J. Z., Park, J., Kim, H. 2022

  Abstract

  BACKGROUND: The Association Research Circulation Osseous (ARCO) developed a novel classification for early-stage (pre-collapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous three classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications.METHODS: In the novel classification, necrotic lesions were classified into three types: Type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; Type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and Type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on CT imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi square tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH.RESULTS: In the derivation cohort, inter-observer reliability (k=0.545) and intra-observer agreement (63 to 100%) of the novel method were higher than the other three classifications. The novel classification system was best able to predict future collapse (p<0.05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (AUC =0.692[0.522-0.863], p<0.05) and the validation cohort (AUC=0.742[0.644-0.841], p=2.46x10-5).CONCLUSIONS: This novel classification is a highly reliable and valid method of those examined. ARCO recommends using this method as a unified classification for early-stage ONFH.

  View details for DOI 10.1016/j.arth.2022.02.009

  View details for PubMedID 35151809

• Macrophage Polarization and the Osteoimmunology of Periprosthetic Osteolysis. Current osteoporosis reports Goodman, S. B., Gibon, E., Gallo, J., Takagi, M. 2022

  Abstract

  PURPOSE OF REVIEW: Joint replacement has revolutionized the treatment of end-stage arthritis. We highlight the key role of macrophages in the innate immune system in helping to ensure that the prosthesis-host interface remains biologically robust.RECENT FINDINGS: Osteoimmunology is of great interest to researchers investigating the fundamental biological and material aspects of joint replacement. Constant communication between cells of the monocyte/macrophage/osteoclast lineage and the mesenchymal stem cell-osteoblast lineage determines whether a durable prosthesis-implant interface is obtained, or whether implant loosening occurs. Tissue and circulating monocytes/macrophages provide local surveillance of stimuli such as the presence of byproducts of wear and can quickly polarize to pro- and anti-inflammatory phenotypes to re-establish tissue homeostasis. When these mechanisms fail, periprosthetic osteolysis results in progressive bone loss and painful failure of mechanical fixation. Immune modulation of the periprosthetic microenvironment is a potential intervention to facilitate long-term durability of prosthetic interfaces.

  View details for DOI 10.1007/s11914-022-00720-3

  View details for PubMedID 35133558

• Staging Bilateral Total Knee Arthroplasties Reduces Alignment Outliers. The Journal of arthroplasty Follett, M. A., Arora, P., Maloney, W. J., Goodman, S. B., Huddleston, J. I., Amanatullah, D. F. 1800

  Abstract

  PURPOSE: Patients frequently present with bilateral symptomatic knee osteoarthritis and request simultaneous total knee arthroplasties (TKAs). Technical differences between simultaneous and staged TKAs could affect clinical and radiographic outcomes. We hypothesized staged TKAs would have fewer mechanical alignment outliers than simultaneous TKAs.METHODS: We reviewed 87 simultaneous and 72 staged TKAs with at least 2 years of follow-up. Radiographic assessment was done using standing long leg and lateral radiographs of the knee. Coronal and sagittal measurements were performed by four blinded observers on two separate occasions with an intra-observer agreement of 0.95 and inter-observer of 0.92.RESULTS: The first simultaneous knee had no difference in the probability of establishing the mechanical axis outside 3° of neutral (45%) compared to the first staged knee (54%, p = 0.337). However, the second simultaneous knee (49%) was more likely to establish the axis outside mechanical neutral compared to the second staged knee (28%; Odds Ratio (OR): 2.54, Confidence Interval (CI): 1.31 - 4.94, p = 0.006). There was an increased risk of deep venous thrombosis with staged TKA (OR: 2.96, CI: 1.28 - 6.84, p = 0.011), but other perioperative complication rates were not significantly different. There were no clinically significant differences in range of motion or Knee Society Score.CONCLUSION: There is a significantly increased risk of establishing the second knee outside mechanical neutral during a simultaneous TKA compared to staged bilateral TKAs, possibly related to a number of surgeon- and system-related factors. The impact on clinical outcomes and radiographic loosening may become significant in long-term follow up.

  View details for DOI 10.1016/j.arth.2022.01.003

  View details for PubMedID 35017050

• Dental Pulp-Derived Stem Cells Are as Effective as Bone Marrow-Derived Mesenchymal Stromal Cells When Implanted into a Murine Critical Bone Defect. Current stem cell research & therapy Vater, C., Männel, C., Bolte, J., Tian, X., Goodman, S. B., Zwingenberger, S. 2022

  Abstract

  Background While bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been used for many years in bone tissue engineering applications, the procedure still has drawbacks such as painful collection methods and damage to the donor site. Dental pulp-derived stem cells (DPSCs) are readily accessible, occur in high amounts and show a high proliferation and differentiation capability. Therefore, DPSCs may be a promising alternative for BM-MSCs to repair bone defects. Objective The aim of this study was to investigate the bone regenerative potential of DPSCs in comparison to BM-MSCs in vitro and in vivo. Methods In vitro investigations included analysis of cell doubling time as well as proliferation and osteogenic differentiation. For the in vivo study 36 male NMRI nude mice were randomized into 3 groups: 1) control (cell-free mineralized collagen matrix (MCM) scaffold), 2) MCM + DPSCs and 3) MCM + BM-MSCs. Critical size 2 mm bone defects were created at the right femur of each mouse and stabilized by an external fixator. After 6 weeks animals were euthanized and microcomputed tomography scans (µCT) and histological analyses were performed. Results In vitro DPSCs showed a 2-fold lower population doubling time and a 9-fold higher increase in proliferation when seeded onto MCM scaffolds as compared to BM-MSCs, but DPSCs showed a significantly lower osteogenic capability than BM-MSCs. In vivo, the healing of the critical bone defect in NMRI nude mice was comparable among all groups. Conclusions Pre-seeding of MCM scaffolds with DPSCs and BM-MSCs did not enhance bone defect healing.

  .

  View details for DOI 10.2174/1574888X17666220215100732

  View details for PubMedID 35168511

• Sex differences in the therapeutic effect of unaltered versus NFkappaB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss. Frontiers in bioengineering and biotechnology Shen, H., Kushioka, J., Toya, M., Utsunomiya, T., Hirata, H., Huang, E. E., Tsubosaka, M., Gao, Q., Li, X., Teissier, V., Zhang, N., Goodman, S. B. 2022; 10: 962114

  Abstract

  Wear particles from joint arthroplasties induce chronic inflammation associated with prolonged upregulation of nuclear factor kappa-B (NF-kappaB) signaling in macrophages and osteoclasts, which leads to osteolysis and implant loosening. Mesenchymal stromal cell (MSC)-based therapy showed great potential for immunomodulation and mitigation of osteolysis in vivo, especially in the chronic phase of inflammation. We previously generated genetically modified MSCs that secrete the anti-inflammatory cytokine interleukin 4 (IL-4) in response to NF-kappaB activation (NFkappaB-IL-4 MSCs). However, whether the impact of sexual difference in the internal environment can alter the therapeutic effects of IL-4 over-secreting MSCs that simultaneously mitigate prolonged inflammation and enhance bone formation remains unknown. This study investigated the therapeutic effects of unaltered MSCs versus NFkappaB-IL-4 MSCs in mitigating chronic inflammation and enhancing bone formation in male and female mice. The murine model was established by continuous infusion of polyethylene particles contaminated with lipopolysaccharide (cPE) into the medullary cavity of the distal femur for 6 weeks to induce chronic inflammation. Unaltered MSCs or NFkappaB-IL-4 MSCs were infused into the femoral intramedullary cavity in sex-matched groups beginning 3 weeks after primary surgery. Femurs were harvested at 6 weeks, and bone marrow density was measured with micro-computational tomography. Numbers of osteoclast-like cells, osteoblasts, and macrophages were evaluated with histochemical and immunofluorescence staining. cPE infusion resulted in severe bone loss at the surgery site, increased tartrate-resistant acid phosphatase positive osteoclasts and M1 pro-inflammatory macrophages, and decreased alkaline phosphatase expression. MSC-based therapy effectively decreased local bone loss and polarized M1 macrophages into an M2 anti-inflammatory phenotype. In females, unaltered MSCs demonstrated a larger impact in enhancing the osteogenesis, but they demonstrated similar anti-inflammatory effects compared to NFkappaB-IL-4 MSCs. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments in a sexually dimorphic manner, which could be an efficacious therapeutic strategy for treatment of periprosthetic osteolysis in both genders.

  View details for DOI 10.3389/fbioe.2022.962114

  View details for PubMedID 36046680

• Notching of the Neck After Acetabular Constraint Necessitating Femoral Component Revision. Arthroplasty today Bonano, J. C., Bala, A., Chen, F., Amanatullah, D. F., Goodman, S. B. 2021; 12: 32-35

  Abstract

  A 75-year-old woman who had previously undergone a left revision total hip arthroplasty with the use of a constrained acetabular liner presented with recurrent dislocation of the hip. Intraoperatively, there was metallic staining of the hip capsule and significant notching of the femoral neck, consistent with impingement of the intact locking ring, necessitating stem revision. Constrained acetabular liners have high failure rates due to intraprosthetic impingement, but to our knowledge, failure due to notching of the femoral component and metallosis from repeated impingement has not been described. Surgeons should be aware of this potential mode of failure.

  View details for DOI 10.1016/j.artd.2021.09.007

  View details for PubMedID 34761091

• Macrophages Modulate the Function of MSC- and iPSC-Derived Fibroblasts in the Presence of Polyethylene Particles. International journal of molecular sciences Gao, Q., Li, Z., Rhee, C., Xiang, S., Maruyama, M., Huang, E. E., Yao, Z., Bunnell, B. A., Tuan, R. S., Lin, H., Gold, M. S., Goodman, S. B. 2021; 22 (23)

  Abstract

  Fibroblasts in the synovial membrane secrete molecules essential to forming the extracellular matrix (ECM) and supporting joint homeostasis. While evidence suggests that fibroblasts contribute to the response to joint injury, the outcomes appear to be patient-specific and dependent on interactions between resident immune cells, particularly macrophages (Mphis). On the other hand, the response of Mphis to injury depends on their functional phenotype. The goal of these studies was to further explore these issues in an in vitro 3D microtissue model that simulates a pathophysiological disease-specific microenvironment. Two sources of fibroblasts were used to assess patient-specific influences: mesenchymal stem cell (MSC)- and induced pluripotent stem cell (iPSC)-derived fibroblasts. These were co-cultured with either M1 or M2 Mphis, and the cultures were challenged with polyethylene particles coated with lipopolysaccharide (cPE) to model wear debris generated from total joint arthroplasties. Our results indicated that the fibroblast response to cPE was dependent on the source of the fibroblasts and the presence of M1 or M2 Mphis: the fibroblast response as measured by gene expression changes was amplified by the presence of M2 Mphis. These results demonstrate that the immune system modulates the function of fibroblasts; furthermore, different sources of differentiated fibroblasts may lead to divergent results. Overall, our research suggests that M2 Mphis may be a critical target for the clinical treatment of cPE induced fibrosis.

  View details for DOI 10.3390/ijms222312837

  View details for PubMedID 34884641

• Effect on Osteogenic Differentiation of Genetically Modified IL4 or PDGF-BB Over-Expressing and IL4-PDGF-BB Co-Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro. Bioengineering (Basel, Switzerland) Tsubosaka, M., Maruyama, M., Huang, E. E., Zhang, N., Utsunomiya, T., Gao, Q., Shen, H., Li, X., Kushioka, J., Hirata, H., Yao, Z., Yang, Y. P., Goodman, S. B. 2021; 8 (11)

  Abstract

  The use of genetically modified (GM) mesenchymal stromal cells (MSCs) and preconditioned MSCs (pMSCs) may provide further opportunities to improve the outcome of core decompression (CD) for the treatment of early-stage osteonecrosis of the femoral head (ONFH). GM interleukin-4 (IL4) over-expressing MSCs (IL4-MSCs), platelet-derived growth factor (PDGF)-BB over-expressing MSCs (PDGF-BB-MSCs), and IL4-PDGF-BB co-over-expressing MSCs (IL4-PDGF-BB-MSCs) and their respective pMSCs were used in this in vitro study and compared with respect to cell proliferation and osteogenic differentiation. IL4-MSCs, PDGF-BB-MSCs, IL4-PDGF-BB-MSCs, and each pMSC treatment significantly increased cell proliferation compared to the MSC group alone. The percentage of Alizarin red-stained area in the IL4-MSC and IL4-pMSC groups was significantly lower than in the MSC group. However, the percentage of Alizarin red-stained area in the PDGF-BB-MSC group was significantly higher than in the MSC and PDGF-BB-pMSC groups. The percentage of Alizarin red-stained area in the IL4-PDGF-BB-pMSC was significantly higher than in the IL4-PDGF-BB-MSC group. There were no significant differences in the percentage of Alizarin red-stained area between the MSC and IL4-PDGF-BB-pMSC groups. The use of PDGF-BB-MSCs or IL4-PDGF-BB-pMSCs increased cell proliferation. Furthermore, PDGF-BB-MSCs promoted osteogenic differentiation. The addition of GM MSCs may provide a useful supplementary cell-based therapy to CD for treatment of ONFH.

  View details for DOI 10.3390/bioengineering8110165

  View details for PubMedID 34821731

• Applying Deep Learning to Quantify Empty Lacunae in Histologic Sections of Osteonecrosis of the Femoral Head. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Lui, E., Maruyama, M., Guzman, R. A., Moeinzadeh, S., Pan, C., Pius, A. K., Quig, M. S., Wong, L. E., Goodman, S. B., Yang, Y. P. 2021

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a disease in which inadequate blood supply to the subchondral bone causes death of cells in the bone marrow. Decalcified histology and assessment of the percentage of empty lacunae are used to quantify the severity of ONFH. However, the current clinical practice of manually counting cells is a tedious and inefficient process. We utilized the power of artificial intelligence by training an established deep convolutional neural network framework, Faster-RCNN, to automatically classify and quantify osteocytes (healthy and pyknotic) and empty lacunae in 135 histology images. The adjusted correlation coefficient between the trained cell classifier and the ground truth was R = 0.98. The methods detailed in this work significantly reduced the manual effort of cell counting in ONFH histological samples and can be translated to other fields of image quantification. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.25201

  View details for PubMedID 34676596

• CORR Insights: Highly Crosslinked Polyethylene Liners Have Negligible Wear at 10 Years: A Radiostereometric Analysis Study. Clinical orthopaedics and related research Goodman, S. B. 2021

  View details for DOI 10.1097/CORR.0000000000002014

  View details for PubMedID 34652288

• The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits. Stem cell research & therapy Guzman, R. A., Maruyama, M., Moeinzadeh, S., Lui, E., Zhang, N., Storaci, H. W., Tam, K., Huang, E. E., Utsunomiya, T., Rhee, C., Gao, Q., Yao, Z., Yang, Y. P., Goodman, S. B. 2021; 12 (1): 503

  Abstract

  BACKGROUND: Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH.METHODS: In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed.RESULTS: In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P<0.001) and CMV-PDGF-BB-MSCs (P<0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P<0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14days (P<0.01), and osteogenic differentiation at 28days (P=0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P=0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P<0.001), greater osteoclast density (P<0.01), and greater angiogenesis (P<0.01) than the other treatment groups.CONCLUSION: The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

  View details for DOI 10.1186/s13287-021-02572-7

  View details for PubMedID 34526115

• Nonoperative and Operative Bone and Cartilage Regeneration and Orthopaedic Biologics of the Hip: An Orthoregeneration Network (ON) Foundation Hip Review. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Hernigou, J., Verdonk, P., Homma, Y., Verdonk, R., Goodman, S. B., Hernigou, P. 2021

  Abstract

  Orthoregeneration is defined as a solution for orthopedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include: drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the hip, including osteonecrosis (aseptic necrosis) involving bone marrow, bone, and cartilage, and chondral injuries involving articular cartilage, synovium, and bone marrow. Promising and established treatment modalities for osteonecrosis include non-weight bearing; pharmacological treatments including low molecular-weight heparin, prostacyclin, statins, bisphophonates, and denosumab, a receptor activator of nuclear factor-kB ligand (RANKL) inhibitor; extracorporeal shock wave therapy; pulsed electromagnetic fields; core decompression surgery; cellular therapies including bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs aka mesenchymal stem cells) and bone marrow autologous concentrate (BMAC), with or without expanded or cultured cells, and possible addition of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF); and arterial perfusion of MSCs which may be combined with addition of carriers or scaffolds including autologous MSCs cultured with beta-tricalcium phosphate (b-TCP) ceramics associated with a free vascularized fibula. Promising and established treatment modalities for chondral lesions include autologous platelet-rich plasma (PRP); hyaluronic acid (HA); MSCs (in expanded or non-expanded form) derived from bone marrow or other sources such as fat, placenta, umbilical cord blood, synovial membrane, and cartilage; microfrature or microfracture augmented with membrane containing MSCs, collagen, HA, or synthetic polymer; mosaicpasty; one-stage autologous cartilage translation (ACT) or two-stage ACT using three-dimensional spheroids; and autologous cartilage grafting; chondral flap repair, or flap fixation with fibrin glue. Hip pain is catastrophic in young patients, and promising therapies offer an alternative to premature arthroplasty. This may address both physical and psychological components of pain the goal is to avoid or postpone an artificial joint. LEVEL OF EVIDENCE: Level V, expert opinion. Hip Orthoregeneration for Osteonecrosis and Chondral Defects.

  View details for DOI 10.1016/j.arthro.2021.08.032

  View details for PubMedID 34506886

• Single-cell Profiling of B and T Cell Repertoire and Gene Expression in the RA Synovium Reveals Tissue Specific Clonal Expansion Meednu, N., Wagner, A., Dunlap, G., Zhang, F., Jonsson, A., Wei, K., Utz, P., Robinson, W., Maecker, H., James, J., Guthridge, J., Bridges, S., Bykerk, V., Donlin, L., Goodman, S., DiCarlo, E., Ritchlin, C., Tabechian, D., Lederer, J., Gravallese, E., McGeachy, M., Firestein, G., Boyle, D., Gregersen, P., Horowitz, D., Perlman, H., Mandelin, A., Bathon, J., Geraldino--Pardilla, L., Hughes, L., Holers, V., Deane, K., Moreland, L., Filer, A., Pitzalis, C., Forbess, L., Ben-Artzi, A., Salomon-Escoto, K., Raychaudhuri, S., Brenner, M., Rao, D., McDavid, A., Anolik, J., Medicines, A. WILEY. 2021: 951-952

  View details for Web of Science ID 000744545201215

• Use of Total Hip Arthroplasty in Patients Under 21 Years Old: A US Population Analysis Gibbons, J., Kahlenberg, C., Jannat--Khah, D., Goodman, S., Mandl, L., Sculco, P., Goodman, S., Figgie, M., Mehta, B. WILEY. 2021: 3396-3399

  View details for Web of Science ID 000744545206192

• Use of Total Hip Arthroplasty in Patients Under 21 Years Old: A US Population Analysis. The Journal of arthroplasty Kahlenberg, C. A., Gibbons, J. A., Jannat-Khah, D. P., Goodman, S. M., Mandl, L. A., Sculco, P. K., Goodman, S. B., Figgie, M. P., Mehta, B. Y. 2021

  Abstract

  BACKGROUND: The purpose of this study is to evaluate trends in the use of total hip arthroplasty (THA) in the United States in patients under 21 years of age. Specifically, we examined the frequency of THA in this patient population over the past 2 decades, the epidemiologic characteristics of patients under 21 who underwent THA, and the characteristics of the hospitals where these procedures were performed.METHODS: We retrospectively reviewed the Kids' Inpatient Database, an inpatient US national weighted sample of hospital admissions in patients under 21 from approximately 4200 hospitals in 46 states. We queried the database using Current Procedural Terminology codes for elective and non-elective primary THA for the years 2000-2016. We utilized the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes to determine primary diagnoses.RESULTS: The weighted total number of THAs performed in patients under 21 in the Kids' Inpatient Database increased from 347 in 2000 to 551 in 2016. The most common diagnoses were osteonecrosis, osteoarthritis, and inflammatory arthritis. The frequency of THA for osteonecrosis increased from 24% in 2000 to 38% in 2016, while the frequency of THA for inflammatory arthritis decreased from 27% in 2000 to 4% in2016.CONCLUSION: The number of THAs in patients under 21 in the United States has increased over the past 2 decades and these procedures are increasingly performed in urban teaching hospitals. The decrease in THA for inflammatory arthritis in this population likely reflects improvements in medical management during the study period.

  View details for DOI 10.1016/j.arth.2021.08.004

  View details for PubMedID 34456091

• The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits. Biomaterials Maruyama, M., Moeinzadeh, S., Guzman, R. A., Zhang, N., Storaci, H. W., Utsunomiya, T., Lui, E., Huang, E. E., Rhee, C., Gao, Q., Yao, Z., Takagi, M., Yang, Y. P., Goodman, S. B. 2021; 275: 120972

  Abstract

  Cell-based therapy for augmentation of core decompression (CD) using mesenchymal stromal cells (MSCs) is a promising treatment for early stage osteonecrosis of the femoral head (ONFH). Recently, the therapeutic potential for immunomodulation of osteogenesis using preconditioned (with pro-inflammatory cytokines) MSCs (pMSCs), or by the timely resolution of inflammation using MSCs that over-express anti-inflammatory cytokines has been described. Here, pMSCs exposed to tumor necrosis factor-alpha and lipopolysaccharide for 3 days accelerated osteogenic differentiation in vitro. Furthermore, injection of pMSCs encapsulated with injectable hydrogels into the bone tunnel facilitated angiogenesis and osteogenesis in the femoral head in vivo, using rabbit bone marrow-derived MSCs and a model of corticosteroid-associated ONFH in rabbits. In contrast, in vitro and in vivo studies demonstrated that genetically-modified MSCs that over-express IL4 (IL4-MSCs), established by using a lentiviral vector carrying the rabbit IL4 gene under the cytomegalovirus promoter, accelerated proliferation of MSCs and decreased the percentage of empty lacunae in the femoral head. Therefore, adjunctive cell-based therapy of CD using pMSCs and IL4-MSCs may hold promise to heal osteonecrotic lesions in the early stage ONFH. These interventions must be applied in a temporally sensitive fashion, without interfering with the mandatory acute inflammatory phase of bone healing.

  View details for DOI 10.1016/j.biomaterials.2021.120972

  View details for PubMedID 34186237

• Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment. Journal of Korean medical science Hines, J. T., Jo, W. L., Cui, Q., Mont, M. A., Koo, K. H., Cheng, E. Y., Goodman, S. B., Ha, Y. C., Hernigou, P., Jones, L. C., Kim, S. Y., Sakai, T., Sugano, N., Yamamoto, T., Lee, M. S., Zhao, D., Drescher, W., Kim, T. Y., Lee, Y. K., Yoon, B. H., Baek, S. H., Ando, W., Kim, H. S., Park, J. W. 2021; 36 (24): e177

  Abstract

  Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

  View details for DOI 10.3346/jkms.2021.36.e177

  View details for PubMedID 34155839

• Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence-Based Clinical Practice Guidelines SURGICAL TECHNOLOGY INTERNATIONAL-INTERNATIONAL DEVELOPMENTS IN SURGERY AND SURGICAL RESEARCH Cheng, E. Y., Cui, Q., Goodman, S. B., Ando, W., Baek, S., Bakker, C., Drescher, W., Hernigou, P., Jones, L. C., Kim, H., Kim, S., Kim, T., Ha, Y., Koo, K., Lee, M. S., Mont, M. A., Reichert, I., Sakai, T., Salem, H. S., Sierra, R. J., Stronach, B., Sugano, N., Yamamoto, T., Yoon, B., Zhao, D. 2021; 38

  View details for Web of Science ID 000661729000045

• Concentrated autologous bone marrow aspirate is not "stem cell" therapy in the repair of nonunions and bone defects. Biomaterials and biosystems Goodman, S. B., Zwingenberger, S. 2021; 2: 100017

  Abstract

  Autogenous bone grafting is the gold standard for replacing large bone defects. Due to limitations in the quantity and quality of harvested bone from the iliac crest, and the potential associated morbidity, the technique of cell grafting has been developed. Autogenous bone marrow aspirate is concentrated (so called BMAC) and delivered locally to the intended site with minimally invasive techniques. However, there are only about 1 in 30,000 Colony Forming Unit-Fibroblast (CFU-F) progenitor cells in unconcentrated iliac crest aspirate. Current techniques for cell concentration only increase these numbers by about 5-fold. Thus, BMAC is not equivalent to "stem cell therapy".

  View details for DOI 10.1016/j.bbiosy.2021.100017

  View details for PubMedID 36824655

  View details for PubMedCentralID PMC9934489

• Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence-Based Clinical Practice Guidelines. Surgical technology international Cheng, E. Y., Cui, Q., Goodman, S. B., Ando, W., Baek, S., Bakker, C., Drescher, W., Hernigou, P., Jones, L. C., Kim, H., Kim, S., Kim, T., Ha, Y., Koo, K., Lee, M. S., Mont, M. A., Reichert, I., Sakai, T., Salem, H. S., Sierra, R. J., Stronach, B., Sugano, N., Yamamoto, T., Yoon, B., Zhao, D. 2021; 38

  Abstract

  INTRODUCTION: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines.MATERIALS AND METHODS: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: 1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; 2) What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and 3) What is the best treatment strategy for patients who have post-collapse disease? The Patient, Intervention, Comparison, and Outcome (PICO) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH.DISCUSSION: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.

  View details for PubMedID 34043232

• Perioperative Statin Use May Reduce Postoperative Arrhythmia Rates After Total Joint Arthroplasty. The Journal of arthroplasty Bonano, J. C., Aratani, A. K., Sambare, T. D., Goodman, S. B., Huddleston, J. I., Maloney, W. J., Burk, D. R., Aaronson, A. J., Finlay, A. K., Amanatullah, D. F. 2021

  Abstract

  BACKGROUND: Postoperative arrhythmias are associated with increased morbidity and mortality in total joint arthroplasty (TJA) patients. HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) decrease atrial fibrillation rates after cardiac surgery, but it is unknown if this cardioprotective effect is maintained after joint reconstruction surgery. We aim to determine if perioperative statin use decreases the incidence of 90-day postoperative arrhythmias in patients undergoing primary TJA.METHODS: We performed a single-center retrospective cohort study in which 231 primary TJA patients (109 hips, 122 knees) received simvastatin 80 mg daily during their hospitalization as part of a single surgeon's standard postoperative protocol. This cohort was matched to 966 primary TJA patients (387 hips and 579 knees) that did not receive simvastatin. New-onset arrhythmias (bradycardia, atrial fibrillation/tachycardia/flutter, paroxysmal supraventricular tachycardia, and ventricular tachycardia) and complications (readmissions, thromboembolism, infection, and dislocation) within 90 days of the procedure were documented. Categorical variables were analyzed using Fisher's exact tests. Our study was powered to detect a 3% difference in arrhythmia rates.RESULTS: Within 90 days postoperatively, arrhythmias occurred in 1 patient (0.4%) who received a perioperative statin, 39 patients (4.0%) who did not receive statins (P= .003), and 24 patients (4.2%) who were on outpatient statins (P= .005). This is 10-fold reduction in the relative risk of developing a postoperative arrhythmia within 90 days of arthroplasty and an absolute risk reduction of 3.6%.CONCLUSION: Treating as few as 28 patients with perioperative simvastatin prevents one new cardiac arrhythmia within 90 days in statin-naive patients undergoing TJA.

  View details for DOI 10.1016/j.arth.2021.05.022

  View details for PubMedID 34127349

• Effect of porosity of a functionally-graded scaffold for the treatment of corticosteroid-associated osteonecrosis of the femoral head in rabbits. Journal of orthopaedic translation Maruyama, M., Pan, C., Moeinzadeh, S., Storaci, H. W., Guzman, R. A., Lui, E., Ueno, M., Utsunomiya, T., Zhang, N., Rhee, C., Yao, Z., Takagi, M., Goodman, S. B., Yang, Y. P. 2021; 28: 90–99

  Abstract

  Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits.Methods: Two different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and beta-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20​mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed.Results: The actual porosity and pore size of the middle segments were 26.4%​±​2.3% and 699​±​56​mum in the 30% porosity FGS, and 56.0%​±​4.5% and 999​±​71​mum in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9%​±​15.8%, which was significantly higher than 39.5%​±​13.0% in the CD group on microCT (p​<​0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3%​±​30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4​±​192.3​N/mm3, which was significantly higher than 338.7​±​164.6​N/mm3 in the 60% porosity FGS group during push-out testing (p​<​0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group.Conclusion: These findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS.Translation potential statement: The translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.

  View details for DOI 10.1016/j.jot.2021.01.002

  View details for PubMedID 33816112

• The Effects of Macrophage Phenotype on Osteogenic Differentiation of MSCs in the Presence of Polyethylene Particles BIOMEDICINES Gao, Q., Rhee, C., Maruyama, M., Li, Z., Shen, H., Zhang, N., Utsunomiya, T., Huang, E., Yao, Z., Bunnell, B. A., Lin, H., Tuan, R. S., Goodman, S. B. 2021; 9 (5)

  View details for DOI 10.3390/biomedicines9050499

  View details for Web of Science ID 000653426000001

• MSC-BASED THERAPY MITIGATES WEAR PARTICLE-INDUCED CHRONIC INFLAMMATION AND ASSOCIATED BONE LOSS IN MICE Zhang, N., Utsunomiya, T., Lin, T. D., Kohno, Y., Ueno, M., Maruyama, M., Huang, E., Rhee, C., Gao, Q., Guzman, R. A., Yao, Z., Goodman, S. B. ELSEVIER SCI LTD. 2021: S34-S35

  View details for Web of Science ID 000650965900029

• The Effects of Macrophage Phenotype on Osteogenic Differentiation of MSCs in the Presence of Polyethylene Particles. Biomedicines Gao, Q., Rhee, C., Maruyama, M., Li, Z., Shen, H., Zhang, N., Utsunomiya, T., Huang, E. E., Yao, Z., Bunnell, B. A., Lin, H., Tuan, R. S., Goodman, S. B. 2021; 9 (5)

  Abstract

  Wear debris generated from the bearing surfaces of joint arthroplasties leads to acute and chronic inflammation, which is strongly associated with implant failure. Macrophages derived from monocytes recruited to the local tissues have a significant impact on bone healing and regeneration. Macrophages can adopt various functional phenotypes. While M1 macrophages are pro-inflammatory, M2 macrophages express factors important for tissue repair. Here, we established a 3D co-culture system to investigate how the immune system influences the osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of micron-sized particles. This system allowed for the simulation of an inflammatory reaction via the addition of Lipopolysaccharide-contaminated polyethylene particles (cPE) and the characterization of bone formation using micro-CT and gene and protein expression. Co-cultures of MSCs with M2 macrophages in the presence of cPE in a 3D environment resulted in the increased expression of osteogenic markers, suggesting facilitation of bone formation. In this model, the upregulation of M2 macrophage expression of immune-associated genes and cytokines contributes to enhanced bone formation by MSCs. This study elucidates how the immune system modulates bone healing in response to an inflammatory stimulus using a unique 3D culture system.

  View details for DOI 10.3390/biomedicines9050499

  View details for PubMedID 34062822

• 3D Printing in alloy design to improve biocompatibility in metallic implants. Materials today (Kidlington, England) Mitra, I., Bose, S., Dernell, W. S., Dasgupta, N., Eckstrand, C., Herrick, J., Yaszemski, M. J., Goodman, S. B., Bandyopadhyay, A. 2021; 45: 20-34

  Abstract

  3D Printing (3DP) or additive manufacturing (AM) enables parts with complex shapes, design flexibility, and customization opportunities for defect specific patient-matched implants. 3DP or AM also offers a design platform that can be used to innovate novel alloys for application-specific compositional modifications. In medical applications, the biological response from a host tissue depends on a biomaterial's structural and compositional properties in the physiological environment. Application of 3DP can pave the way towards manufacturing innovative metallic implants, combining structural variations at different length scales and tailored compositions designed for specific biological responses. This study shows how 3DP can be used to design metallic alloys for orthopedic and dental applications with improved biocompatibility using in vitro and in vivo studies. Titanium (Ti) and its alloys are used extensively in biomedical devices due to excellent fatigue and corrosion resistance and good strength to weight ratio. However, Ti alloys' in vivo biological response is poor due to its bioinert surface. Different coatings and surface modification techniques are currently being used to improve the biocompatibility of Ti implants. We focused our efforts on improving Ti's biocompatibility via a combination of tantalum (Ta) chemistry in Ti, the addition of designed micro-porosity, and nanoscale surface modification to enhance both in vitro cytocompatibility and early stage in vivo osseointegration, which was studied in rat and rabbit distal femur models.

  View details for DOI 10.1016/j.mattod.2020.11.021

  View details for PubMedID 34220288

  View details for PubMedCentralID PMC8248902

• 3D Printing in alloy design to improve biocompatibility in metallic implants MATERIALS TODAY Mitra, I., Bose, S., Dernell, W. S., Dasgupta, N., Eckstrand, C., Herrick, J., Yaszemski, M. J., Goodman, S. B., Bandyopadhyay, A. 2021; 45: 20-34

  View details for DOI 10.1016/j.mattod.2020.11.021

  View details for Web of Science ID 000659957300007

• Cell spheroids are as effective as single cells suspensions in the treatment of critical-sized bone defects. BMC musculoskeletal disorders Findeisen, L., Bolte, J., Vater, C., Petzold, C., Quade, M., Muller, L., Goodman, S. B., Zwingenberger, S. 2021; 22 (1): 401

  Abstract

  BACKGROUND: Due to their multilineage potential and high proliferation rate, mesenchymal stem cells (MSC) indicate a sufficient alternative in regenerative medicine. In comparison to the commonly used 2-dimensional culturing method, culturing cells as spheroids stimulates the cell-cell communication and mimics the in vivo milieu more accurately, resulting in an enhanced regenerative potential. To investigate the osteoregenerative potential of MSC spheroids in comparison to MSC suspensions, cell-loaded fibrin gels were implanted into murine critical-sized femoral bone defects.METHODS: After harvesting MSCs from 4 healthy human donors and preculturing and immobilizing them in fibrin gel, cells were implanted into 2mm murine femoral defects and stabilized with an external fixator. Therefore, 26 14- to 15-week-old nu/nu NOD/SCID nude mice were randomized into 2 groups (MSC spheroids, MSC suspensions) and observed for 6weeks. Subsequently, micro-computed tomography scans were performed to analyze regenerated bone volume and bone mineral density. Additionally, histological analysis, evaluating the number of osteoblasts, osteoclasts and vessels at the defect side, were performed. Statistical analyzation was performed by using the Student's t-test and, the Mann-Whitney test. The level of significance was set at p=0.05.RESULTS: muCT-analysis revealed a significantly higher bone mineral density of the MSC spheroid group compared to the MSC suspension group. However, regenerated bone volume of the defect side was comparable between both groups. Furthermore, no significant differences in histological analysis between both groups could be shown.CONCLUSION: Our in vivo results reveal that the osteo-regenerative potential of MSC spheroids is similar to MSC suspensions.

  View details for DOI 10.1186/s12891-021-04264-y

  View details for PubMedID 33941144

• Articulating vs Static Spacers for Native Knee Infection in the Setting of Degenerative Joint Disease. Arthroplasty today Hooper, J., Arora, P., Kappagoda, S., Huddleston, J. I., Goodman, S. B., Amanatullah, D. F. 2021; 8: 138–44

  Abstract

  Background: Patients with advanced knee arthritis who develop a septic joint are not adequately treated with irrigation and debridement and intravenous antibiotics because of antecedent cartilage damage. The gold standard treatment has been a 2-stage approach. The periprosthetic joint infection literature has demonstrated the superiority of articulating spacers, and metal-on-poly (MOP) spacers are being used with increasing frequency. The purpose of this study was to compare the postoperative outcomes of patients with infected, arthritic knees treated by a 2-stage approach to those of patients who received single-stage treatment with a MOP spacer.Methods: Sixteen patients with native knee septic arthritis treated with an antibiotic spacer between 1998 and 2019 were reviewed. Demographic data, clinical data, knee motion, Knee Society score, Timed-Up-and-Go, and pain scores were collected. Survivorship of final implants was compared.Results: Six of 16 knees (38%) received single-stage treatment, and 10 received 2-stage treatment (62%). Five of 6 MOP spacers (83%) were retained at a mean follow-up of 3 ± 1.2 years. Nine of 10 (90%) receiving static spacers had subsequent reconstruction, with 9 (100%) surviving at mean follow-up of 7 ± 3.2 years. The patients who received MOP spacers trended toward greater terminal flexion, higher Knee Society score, and faster Timed-Up-and-Go at final follow-up.Conclusion: Infection in a native, arthritic knee may be effectively treated using single-stage MOP spacer. Postoperative outcomes of single-stage MOP spacers compare favorably to staged static spacers and with those undergoing revision surgery for other indications. Longer follow-up is needed to evaluate durability of MOP spacers.

  View details for DOI 10.1016/j.artd.2021.01.009

  View details for PubMedID 33748374

• Suppression of NF-kappaB-induced chronic inflammation mitigates inflammatory osteolysis in the murine continuous polyethylene particle infusion model. Journal of biomedical materials research. Part A Utsunomiya, T., Zhang, N., Lin, T., Kohno, Y., Ueno, M., Maruyama, M., Huang, E., Rhee, C., Yao, Z., Goodman, S. B. 2021

  Abstract

  Wear particle-associated bone loss (periprosthetic osteolysis) constrains the longevity of total joint arthroplasty (TJA). Wear particles induce a prolonged upregulation of nuclear factor kappa B (NF-kappaB) signaling in macrophages and osteoclasts. Synthetic double-stranded oligodeoxynucleotides (ODNs) can prevent the binding of NF-kappaB to the promoter regions of targeted genes and inhibit genetic activation. We tested the hypothesis that polyethylene-particle induced chronic inflammatory bone loss could be suppressed by local delivery of NF-kappaB decoy ODNs in murine in vivo model. Polyethylene particles were continuously infused into the medullary cavity of the distal femur for 6weeks to induce chronic inflammation, and micro-computational tomography and immunohistochemical analysis were performed. Particle-induced chronic inflammation resulted in lower BMD values, an increase in osteoclastogenesis and nuclear translocation of p65, a prolonged M1 pro-inflammatory macrophage phenotype, and a decrease of M2 anti-inflammatory macrophage phenotype. Delayed timing of local infusion of NF-kappaB decoy ODN for the last 3weeks reversed polyethylene-particle associated chronic inflammatory bone loss and facilitated bone healing. This study demonstrated that polyethylene-particle associated chronic inflammatory osteolysis can be effectively modulated via interference with the NF-kappaB pathway; this minimally invasive intervention could potentially be an efficacious therapeutic strategy for periprosthetic osteolysis after TJA.

  View details for DOI 10.1002/jbm.a.37175

  View details for PubMedID 33779115

• A dysfunctional TRPV4-GSK3beta pathway prevents osteoarthritic chondrocytes from sensing changes in extracellular matrix viscoelasticity. Nature biomedical engineering Agarwal, P., Lee, H., Smeriglio, P., Grandi, F., Goodman, S., Chaudhuri, O., Bhutani, N. 2021

  Abstract

  Changes in the composition and viscoelasticity of the extracellular matrix in load-bearing cartilage influence the proliferation and phenotypes of chondrocytes, and are associated with osteoarthritis. However, the underlying molecular mechanism is unknown. Here we show that the viscoelasticity of alginate hydrogels regulates cellular volume in healthy human chondrocytes (with faster stress relaxation allowing cell expansion and slower stress relaxation restricting it) but not in osteoarthritic chondrocytes. Cellular volume regulation in healthy chondrocytes was associated with changes in anabolic gene expression, in the secretion of multiple pro-inflammatory cytokines, and in the modulation of intracellular calcium regulated by the ion-channel protein transient receptor potential cation channel subfamily V member 4 (TRPV4), which controls the phosphorylation of glycogen synthase kinase 3beta (GSK3beta), an enzyme with pleiotropic effects in osteoarthritis. A dysfunctional TRPV4-GSK3beta pathway in osteoarthritic chondrocytes rendered the cells unable to respond to environmental changes in viscoelasticity. Our findings suggest strategies for restoring chondrocyte homeostasis in osteoarthritis.

  View details for DOI 10.1038/s41551-021-00691-3

  View details for PubMedID 33707778

• Modified Kerboul Angle Predicts Outcome of Core Decompression With or Without Additional Cell Therapy. The Journal of arthroplasty Boontanapibul, K., Huddleston, J. I., Amanatullah, D. F., Maloney, W. J., Goodman, S. B. 2021

  Abstract

  BACKGROUND: Core decompression is the most common procedure for early-stage osteonecrosis of the femoral head (ONFH). This study investigated outcomes of core decompression with/without bone marrow aspirate concentrate (BMAC), based on the Kerboul combined necrotic angles using magnetic resonance imaging.METHODS: We reviewed 66 patients (83 hips) with early ONFH, Association Research Circulation Osseous stages I-IIIa, who underwent core decompression alone (26 patients, 33 hips) or in combination with BMAC (40 patients, 50 hips). Survival rate and progressive collapse were analyzed using the Kaplan-Meier method, and conversion to total hip arthroplasty (THA) was evaluated. Subgroup analyses based on the modified Kerboul angle were performed: grade I (<200°), grade II (200°-249°), grade III (250°-299°), and grade IV (≥300°).RESULTS: Mean follow-up was 36±23 months. Femoral head collapse with BMAC (16 hips, 32%) was significantly lower than without BMAC (19 hips, 58%, P= .019). Conversion THA was significantly lower with BMAC (28%) than without (58%, P= .007). Survival rates among groups showed significant differences (P= .017). In grade I, 0/12 hips with BMAC collapsed while 3/9 (33%) without BMAC collapsed (P= .063); in grade II, 2/16 hips (12%) with BMAC collapsed while 7/13 (54%) without BMAC collapsed (P= .023). There was no significant difference in collapse with (64%) or without (82%) BMAC in grade III-IV hips (P= .256).CONCLUSION: Core decompression with/without BMAC had a high failure rate, by increasing disease progression and the necessity for THA, for combined necrotic angles >250°. In our study, addition of BMAC had more reliable outcomes than isolated core decompression for precollapse ONFH if the combined necrotic angles were <250°.

  View details for DOI 10.1016/j.arth.2021.01.075

  View details for PubMedID 33618954

• Management of Morbidity and Mortality in a New Zealand White Rabbit Model of Steroid-Induced Osteonecrosis of the Femoral Head COMPARATIVE MEDICINE Casey, K. M., Gore, F., Vilches-Moure, J. G., Maruyama, M., Goodman, S. B., Yang, Y., Baker, S. W. 2021; 71 (1): 86–98

  Abstract

  Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of SONFH due to its shared femoral vascular anatomy with human patients, relative size of the femoral head, and general fecundity. However, morbidity and mortality are frequent during the steroid induction period, prior to surgical manipulation. These problems are poorly reported and inadequately described in the literature. In this study, we report the clinical, gross, and histopathologic findings of New Zealand white (NZW) rabbits undergoing the steroid induction phase of the SONFH model. Severe weight loss (>30%), lipemia, hypercholesterolemia, hyperglycemia, and elevations in ALT and AST were consistent findings across all rabbits, although these changes did not differentiate asymptomatic rabbits from those that became clinically symptomatic or died. Euthanized and spontaneously deceased rabbits exhibited hepatomegaly, hepatic lipidosis/glycogenosis, and hepatocellular necrosis, in addition to a lipid-rich and proteinaceous thoracic effusion. A subset of rabbits developed opportunistic pulmonary infections with Bordetella bronchiseptica and Escherichia coli and small intestine infections with Lawsonia intracellularis superimposed on hepatic and thoracic disease. Together, these findings allowed us to establish a clinical decision-making flowchart that reduced morbidities and mortalities in a subsequent cohort of SONFH rabbits. Recognition of these model-associated morbidities is critical for providing optimal clinical care during the disease induction phase of SONFH.

  View details for DOI 10.30802/AALAS-CM-20-000071

  View details for Web of Science ID 000620257900005

  View details for PubMedID 33500020

  View details for PubMedCentralID PMC7898173

• Current Models for Development of Disease-Modifying Osteoarthritis Drugs. Tissue engineering. Part C, Methods Makarczyk, M. J., Gao, Q., He, Y., Li, Z., Gold, M. S., Hochberg, M., Bunnell, B., Tuan, R. S., Goodman, S. B., Lin, H. 2021

  Abstract

  Osteoarthritis (OA) is a painful and disabling disease that affects millions of people worldwide. Symptom-alleviating treatments exist, although none with long-term efficacy. Furthermore, there are currently no disease-modifying OA drugs (DMOADs) with demonstrated efficacy in OA patients, which is, in part, attributed to a lack of full understanding of the pathogenesis of OA. The inability to translate findings from basic research to clinical applications also highlights the deficiencies in the available OA models at simulating the clinically relevant pathologies and responses to treatments in humans. In this review, the current status in the development of DMOADs will be first presented, with special attention to those in Phase II-IV clinical trials. Next, current in vitro, ex vivo, and in vivo OA models are summarized and the respective advantages and disadvantages of each are highlighted. Notably, the development and application of microphysiological or tissue-on-a-chip systems for modeling OA in humans are presented and the issues that need to be addressed in the future are discussed. Microphysiological systems should be given serious consideration for their inclusion in the DMOAD development pipeline, both for their ability to predict drug safety and efficacy in human clinical trials at present, as well as for their potential to serve as a test platform for personalized medicine.

  View details for DOI 10.1089/ten.TEC.2020.0309

  View details for PubMedID 33403944

• Response to Letter to the Editor on "Diagnosis of Osteonecrosis of the Femoral Head: Too Little, Too Late, and Independent of Etiology". The Journal of arthroplasty Boontanapibul, K. n., Steere, J. T., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2021; 36 (2): e12–e13

  View details for DOI 10.1016/j.arth.2020.09.037

  View details for PubMedID 33446355

• Sex Differences in Mesenchymal Stem Cell Therapy With Gelatin-Based Microribbon Hydrogels in a Murine Long Bone Critical-Size Defect Model. Frontiers in bioengineering and biotechnology Ueno, M., Zhang, N., Hirata, H., Barati, D., Utsunomiya, T., Shen, H., Lin, T., Maruyama, M., Huang, E., Yao, Z., Wu, J. Y., Zwingenberger, S., Yang, F., Goodman, S. B. 2021; 9: 755964

  Abstract

  Mesenchymal stem cell (MSC)-based therapy and novel biomaterials are promising strategies for healing of long bone critical size defects. Interleukin-4 (IL-4) over-expressing MSCs within a gelatin microribbon (RB) scaffold was previously shown to enhance the bridging of bone within a critical size femoral bone defect in male Balb/c mice. Whether sex differences affect the healing of this bone defect in conjunction with different treatments is unknown. In this study, we generated 2-mm critical-sized femoral diaphyseal bone defects in 10-12-week-old female and male Balb/c mice. Scaffolds without cells and with unmodified MSCs were implanted immediately after the primary surgery that created the bone defect; scaffolds with IL-4 over-expressing MSCs were implanted 3days after the primary surgery, to avoid the adverse effects of IL-4 on the initial inflammatory phase of fracture healing. Mice were euthanized 6weeks after the primary surgery and femurs were collected. MicroCT (CT), histochemical and immunohistochemical analyses were subsequently performed of the defect site. RB scaffolds with IL-4 over-expressing MSCs enhanced bone healing in both female and male mice. Male mice showed higher measures of bone bridging and increased alkaline phosphatase (ALP) positive areas, total macrophages and M2 macrophages compared with female mice after receiving scaffolds with IL-4 over-expressing MSCs. Female mice showed higher Tartrate-Resistant Acid Phosphatase (TRAP) positive osteoclast numbers compared with male mice. These results demonstrated that sex differences should be considered during the application of MSC-based studies of bone healing.

  View details for DOI 10.3389/fbioe.2021.755964

  View details for PubMedID 34738008

• Return to work and productivity loss after surgery: A health economic evaluation. International journal of surgery (London, England) M Hah, J., Lee, E., Shrestha, R., Pirrotta, L., Huddleston, J., Goodman, S., Amanatullah, D. F., Dirbas, F. M., Carroll, I. R., Schofield, D. 2021: 106100

  Abstract

  We aimed to identify preoperative psychosocial factors associated with return-to-work (RTW) and the associated cost of productivity loss due to work absenteeism following surgery. Research demonstrates a high economic burden from productivity loss after surgery, but the comparative cost of productivity loss relative to income across different operations has not been examined.A mixed surgical cohort recruited for a randomized controlled trial were prospectively followed for up to two years following surgery with daily phone assessments to three months, weekly assessments thereafter to six months, then monthly assessments thereafter to determine RTW status, opioid use and pain.183 of 207 (88.3%) patients in paid employment prior to surgery, who provided at least one day of follow-up, were included in this analysis. The average cost of productivity loss due to work absenteeism was $13 761 (median $9064). Patients who underwent total knee replacement incurred the highest income loss. Medical claims filed before surgery were significantly associated with relative income loss (AOR 5.09; 95% CI 1.73-14.96; p < 0.01) and delayed postoperative RTW. Elevated preoperative PTSD symptoms were associated with delayed RTW (HR 0.78; 95%CI 0.63-0.96; p-value = 0.02) while male gender (HR 1.63; 95%CI 1.11-2.38; p-value = 0.01) was associated with faster postoperative RTW.Surgery places a high economic burden on individuals due to postoperative productivity loss. Multidisciplinary approaches, such as pathways, that facilitate the operation and recovery may mitigate the economic consequences for patients, employers, and the healthcare system.

  View details for DOI 10.1016/j.ijsu.2021.106100

  View details for PubMedID 34600123

• Objective Activity Parameters Track Patient-Specific Physical Recovery Trajectories After Surgery and Link With Individual Preoperative Immune States. Annals of surgery Fallahzadeh, R., Verdonk, F., Ganio, E., Culos, A., Stanley, N., Marić, I., Chang, A. L., Becker, M., Phongpreecha, T., Xenochristou, M., De Francesco, D., Espinosa, C., Gao, X., Tsai, A., Sultan, P., Tingle, M., Amanatullah, D. F., Huddleston, J. I., Goodman, S. B., Gaudilliere, B., Angst, M. S., Aghaeepour, N. 2021

  Abstract

  The longitudinal assessment of physical function with high temporal resolution at a scalable and objective level in patients recovering from surgery is highly desirable to understand the biological and clinical factors that drive the clinical outcome. However, physical recovery from surgery itself remains poorly defined and the utility of wearable technologies to study recovery after surgery has not been established.Prolonged postoperative recovery is often associated with long-lasting impairment of physical, mental, and social functions. While phenotypical and clinical patient characteristics account for some variation of individual recovery trajectories, biological differences likely play a major role. Specifically, patient-specific immune states have been linked to prolonged physical impairment after surgery. However, current methods of quantifying physical recovery lack patient specificity and objectivity.Here, a combined high-fidelity accelerometry and state-of-the-art deep immune profiling approach was studied in patients undergoing major joint replacement surgery. The aim was to determine whether objective physical parameters derived from accelerometry data can accurately track patient-specific physical recovery profiles (suggestive of a 'clock of postoperative recovery'), compare the performance of derived parameters with benchmark metrics including step count, and link individual recovery profiles with patients' preoperative immune state.The results of our models indicate that patient-specific temporal patterns of physical function can be derived with a precision superior to benchmark metrics. Notably, six distinct domains of physical function and sleep are identified to represent the objective temporal patterns: "activity capacity" and "moderate and overall activity" (declined immediately after surgery); "sleep disruption and sedentary activity" (increased after surgery); "overall sleep", "sleep onset", and "light activity" (no clear changes were observed after surgery). These patterns can be linked to individual patients' preoperative immune state using cross-validated canonical-correlation analysis. Importantly, the pSTAT3 signal activity in M-MDSCs predicted a slower recovery.Accelerometry-based recovery trajectories are scalable and objective outcomes to study patient-specific factors that drive physical recovery.

  View details for DOI 10.1097/SLA.0000000000005250

  View details for PubMedID 35129529

• Mesenchymal Stem Cells and NF-κB Sensing Interleukin-4 Over-Expressing Mesenchymal Stem Cells Are Equally Effective in Mitigating Particle-Associated Chronic Inflammatory Bone Loss in Mice. Frontiers in cell and developmental biology Zhang, N., Utsunomiya, T., Lin, T., Kohno, Y., Ueno, M., Maruyama, M., Huang, E., Rhee, C., Yao, Z., Goodman, S. B. 2021; 9: 757830

  Abstract

  Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

  View details for DOI 10.3389/fcell.2021.757830

  View details for PubMedID 34722543

  View details for PubMedCentralID PMC8551755

• Provider Personal and Demographic Characteristics and Patient Satisfaction in Orthopaedic Surgery. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews Lu, L. Y., Sharabianlou Korth, M. J., Cheng, R. Z., Finlay, A. K., Kamal, R. N., Goodman, S. B., Maloney, W. J., Huddleston, J. I., Amanatullah, D. F. 2021; 5 (4)

  Abstract

  INTRODUCTION: Patient satisfaction has increasingly been used to assess physician performance and quality of care. Although there is evidence that patient satisfaction is associated with patient-reported health outcomes and communication-related measures, there is debate over the use of patient satisfaction in reimbursement policy. Patient characteristics that influence satisfaction have been studied, but the effects of personal and demographic characteristics of physicians on patient satisfaction have yet to be explored.METHODS: Outpatient satisfaction scores from 11,059 patients who rated 25 orthopaedic surgeons from a single institution were studied. In this study, we sought to explore the relationship between nonmodifiable physician characteristics, such as sex and race, and patient satisfaction with outpatient orthopaedic surgery care, as expressed in the Press Ganey Satisfaction Scores. Univariate logistic regression models were used to test the associations between each provider characteristic and patient satisfaction on the Press Ganey patient satisfaction questionnaire.RESULTS: Three nonmodifiable physician personal and demographic characteristics were markedly associated with lower patient satisfaction scores across overall satisfaction, communication, and empathy domains: (1) female gender, (2) Asian ethnicity, and (3) being unmarried. Asian ethnicity reduced the odds of receiving a 5-star rating for likelihood to recommend the provider by nearly 40%, but none of these nonmodifiable physician personal and demographic characteristics affected the likelihood to recommend the practice.DISCUSSION: Sex, ethnicity, and marital status are nonmodifiable provider characteristics, each associated with markedly lower odds of receiving a 5-star rating on Press Ganey patient satisfaction survey. These data reveal inherent patient biases that negatively affect physician-patient interactions and may exacerbate the lack of diversity in orthopaedic surgery. More research is necessary before using patient satisfaction ratings to evaluate surgeons or as quality measures that affect reimbursement policies.

  View details for DOI 10.5435/JAAOSGlobal-D-20-00198

  View details for PubMedID 33835991

• Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis. Frontiers in immunology Qiu, J., Wu, B., Goodman, S. B., Berry, G. J., Goronzy, J. J., Weyand, C. M. 2021; 12: 652771

  Abstract

  Like other autoimmune diseases, rheumatoid arthritis (RA) develops in distinct stages, with each phase of disease linked to immune cell dysfunction. HLA class II genes confer the strongest genetic risk to develop RA. They encode for molecules essential in the activation and differentiation of T cells, placing T cells upstream in the immunopathology. In Phase 1 of the RA disease process, T cells lose a fundamental function, their ability to be self-tolerant, and provide help for autoantibody-producing B cells. Phase 2 begins many years later, when mis-differentiated T cells gain tissue-invasive effector functions, enter the joint, promote non-resolving inflammation, and give rise to clinically relevant arthritis. In Phase 3 of the RA disease process, abnormal innate immune functions are added to adaptive autoimmunity, converting synovial inflammation into a tissue-destructive process that erodes cartilage and bone. Emerging data have implicated metabolic mis-regulation as a fundamental pathogenic pathway in all phases of RA. Early in their life cycle, RA T cells fail to repair mitochondrial DNA, resulting in a malfunctioning metabolic machinery. Mitochondrial insufficiency is aggravated by the mis-trafficking of the energy sensor AMPK away from the lysosomal surface. The metabolic signature of RA T cells is characterized by the shunting of glucose toward the pentose phosphate pathway and toward biosynthetic activity. During the intermediate and terminal phase of RA-imposed tissue inflammation, tissue-residing macrophages, T cells, B cells and stromal cells are chronically activated and under high metabolic stress, creating a microenvironment poor in oxygen and glucose, but rich in metabolic intermediates, such as lactate. By sensing tissue lactate, synovial T cells lose their mobility and are trapped in the tissue niche. The linkage of defective DNA repair, misbalanced metabolic pathways, autoimmunity, and tissue inflammation in RA encourages metabolic interference as a novel treatment strategy during both the early stages of tolerance breakdown and the late stages of tissue inflammation. Defining and targeting metabolic abnormalities provides a new paradigm to treat, or even prevent, the cellular defects underlying autoimmune disease.

  View details for DOI 10.3389/fimmu.2021.652771

  View details for PubMedID 33868292

• Different Effects of Intramedullary Injection of Mesenchymal Stem Cells During the Acute vs. Chronic Inflammatory Phase on Bone Healing in the Murine Continuous Polyethylene Particle Infusion Model. Frontiers in cell and developmental biology Utsunomiya, T., Zhang, N., Lin, T., Kohno, Y., Ueno, M., Maruyama, M., Rhee, C., Huang, E., Yao, Z., Goodman, S. B. 2021; 9: 631063

  Abstract

  Chronic inflammation is a common feature in many diseases of different organ systems, including bone. However, there are few interventions to mitigate chronic inflammation and preserve host tissue. Previous in vitro studies demonstrated that preconditioning of mesenchymal stem cells (pMSCs) using lipopolysaccharide and tumor necrosis factor-alpha polarized macrophages from a pro-inflammatory to an anti-inflammatory phenotype and increased osteogenesis compared to unaltered MSCs. In the current study, we investigated the local injection of MSCs or pMSCs during the acute versus chronic inflammatory phase in a murine model of inflammation of bone: the continuous femoral intramedullary polyethylene particle infusion model. Chronic inflammation due to contaminated polyethylene particles decreased bone mineral density and increased osteoclast-like cells positively stained with leukocyte tartrate resistant acid phosphatase (TRAP) staining, and resulted in a sustained M1 pro-inflammatory macrophage phenotype and a decreased M2 anti-inflammatory phenotype. Local injection of MSCs or pMSCs during the chronic inflammatory phase reversed these findings. Conversely, immediate local injection of pMSCs during the acute inflammatory phase impaired bone healing, probably by mitigating the mandatory acute inflammatory reaction. These results suggest that the timing of interventions to facilitate bone healing by modulating inflammation is critical to the outcome. Interventions to facilitate bone healing by modulating acute inflammation should be prudently applied, as this phase of bone healing is temporally sensitive. Alternatively, local injection of MSCs or pMSCs during the chronic inflammatory phase may be a potential intervention to mitigate the adverse effects of contaminated particles on bone.

  View details for DOI 10.3389/fcell.2021.631063

  View details for PubMedID 33816480

• Encapsulated Mesenchymal Stromal Cell Microbeads Promote Endogenous Regeneration of Osteoarthritic Cartilage Ex Vivo. Advanced healthcare materials Sahu, N. n., Agarwal, P. n., Grandi, F. n., Bruschi, M. n., Goodman, S. n., Amanatullah, D. n., Bhutani, N. n. 2021: e2002118

  Abstract

  The anti-inflammatory secretome of mesenchymal stromal cells (MSCs) is lucrative for the treatment of osteoarthritis (OA), a disease characterized by low-grade inflammation. However, the precise effects of the MSC secretome on patient-derived OA tissue is lacking. To investigate these effects, alginate encapsulated MSCs are co-cultured with patient-derived OA cartilage explants for 8 days. Proteoglycan distribution in OA cartilage explants examined by Safranin O staining is markedly improved when cultured with MSC microbeads as compared to control OA explants cultured alone. Total sulfated glycosaminoglycan (sGAG) content in OA explants is significantly increased upon co-culture with MSC microbeads on day 8. The sGAG released into the culture media is unchanged by the presence of MSC microbeads, suggesting de novo sGAG synthesis in OA explants. Co-culture with MSC microbeads increased the DNA content and Ki67+ cells in OA explants, indicating proliferation. An increase in secreted cytokines IL-10, HGF, and sFAS assessed by multiplex cytokine assay, increased TIMP1 levels, and reduction in percent apoptotic cells in OA explants is noted. Together, data demonstrates that paracrine factors secreted by alginate encapsulated MSCs microbeads in response to OA cartilage, create an anabolic, proliferative, and anti-apoptotic microenvironment inducing endogenous regeneration in clinically relevant, patient-derived OA cartilage.

  View details for DOI 10.1002/adhm.202002118

  View details for PubMedID 33434393

• PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration. Stem cell research & therapy Zhang, N. n., Lo, C. W., Utsunomiya, T. n., Maruyama, M. n., Huang, E. n., Rhee, C. n., Gao, Q. n., Yao, Z. n., Goodman, S. B. 2021; 12 (1): 40

  Abstract

  Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified MSCs that over-express specific cytokines, growth factors, or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages mitigate chronic inflammation and enhance osteogenesis by MSC lineage cells. However, exposure to IL-4 prematurely inhibits osteogenesis of MSCs in vitro; furthermore, IL-4 overexpressing MSCs inhibit osteogenesis in vivo during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect.In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected MSCs with PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate cell proliferation and viability, protein expression, and the capability for osteogenesis.PDGF-BB and IL-4 co-overexpression was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone.Overexpression of PDGF-BB together with IL-4 mitigates the inhibitory effect of IL-4 on osteogenesis by IL-4 overexpressing MSCS. PDGF-BB and IL-4 overexpressing MSCs may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.

  View details for DOI 10.1186/s13287-020-02086-8

  View details for PubMedID 33413614

• ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head. Journal of Korean medical science Cui, Q. n., Jo, W. L., Koo, K. H., Cheng, E. Y., Drescher, W. n., Goodman, S. B., Ha, Y. C., Hernigou, P. n., Jones, L. C., Kim, S. Y., Lee, K. S., Lee, M. S., Lee, Y. J., Mont, M. A., Sugano, N. n., Taliaferro, J. n., Yamamoto, T. n., Zhao, D. n. 2021; 36 (10): e65

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

  View details for DOI 10.3346/jkms.2021.36.e65

  View details for PubMedID 33724736

• Efficacy of motivational-interviewing and guided opioid tapering support for patients undergoing orthopedic surgery (MI-Opioid Taper): A prospective, assessor-blind, randomized controlled pilot trial. EClinicalMedicine Hah, J. M., Trafton, J. A., Narasimhan, B., Krishnamurthy, P., Hilmoe, H., Sharifzadeh, Y., Huddleston, J. I., Amanatullah, D., Maloney, W. J., Goodman, S., Carroll, I., Mackey, S. C. 2020; 28: 100596

  Abstract

  Background: Postoperative opioid use can lead to chronic use and misuse. Few studies have examined effective approaches to taper postoperative opioid use while maintaining adequate analgesia.Methods: This randomized, assessor-blinded, pilot trial of postoperative motivational interviewing and guided opioid tapering support (MI-Opioid Taper) added to usual care (UC) enrolled patients undergoing total hip or knee arthroplasty at a single U.S. academic medical center. MI-Opioid Taper involved weekly (to seven weeks) and monthly (to one year) phone calls until patient-reported opioid cessation. Opioid tapering involved 25% weekly dose reductions. The primary feasibility outcome was study completion in the group to which participants were randomized. The primary efficacy outcome, time to baseline opioid use, was the first of five consecutive days of return to baseline preoperative dose. Intention-to-treat analysis with Cox proportional hazards regression was adjusted for operation. ClinicalTrials.gov registration: NCT02070003.Findings: From November 26, 2014, to April 27, 2018, 209 patients were screened, and 104 patients were assigned to receive MI-Opioid Taper (49 patients) or UC only (55 patients). Study completion after randomization was similar between groups (96.4%, 53 patients receiving UC, 91.8%, 45 patients receiving MI-Opioid Taper). Patients receiving MI-Opioid Taper had a 62% increase in the rate of return to baseline opioid use after surgery (HR 1.62; 95%CI 1.06-2.46; p=003). No trial-related adverse events occurred.Interpretation: In patients undergoing total joint arthroplasty, MI-Opioid Taper is feasible and future research is needed to establish the efficacy of MI-Opioid Taper to promote postoperative opioid cessation.Funding: National Institute on Drug Abuse.

  View details for DOI 10.1016/j.eclinm.2020.100596

  View details for PubMedID 33294812

• Articular cartilage regeneration by activated skeletal stem cells. Nature medicine Murphy, M. P., Koepke, L. S., Lopez, M. T., Tong, X., Ambrosi, T. H., Gulati, G. S., Marecic, O., Wang, Y., Ransom, R. C., Hoover, M. Y., Steininger, H., Zhao, L., Walkiewicz, M. P., Quarto, N., Levi, B., Wan, D. C., Weissman, I. L., Goodman, S. B., Yang, F., Longaker, M. T., Chan, C. K. 2020

  Abstract

  Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5-7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.

  View details for DOI 10.1038/s41591-020-1013-2

  View details for PubMedID 32807933

• Adipose Tissue-Derived Stem Cells Retain Their Adipocyte Differentiation Potential in Three-Dimensional Hydrogels and Bioreactors . Biomolecules O'Donnell, B. T., Al-Ghadban, S., Ives, C. J., L'Ecuyer, M. P., Monjure, T. A., Romero-Lopez, M., Li, Z., Goodman, S. B., Lin, H., Tuan, R. S., Bunnell, B. A. 2020; 10 (7)

  Abstract

  Osteoarthritis (OA) is a common joint disorder with a significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose tissue has recently been highlighted as a major contributor to OA through strong inflammation mediating effects. In this study, methacrylated gelatin (GelMA) constructs seeded with adipose tissue-derived mesenchymal stem cells (ASCs) and cultured in a 3D printed bioreactor were investigated for use in microphysiological systems to model adipose tissue in the knee joint. Four patient-derived ASC populations were seeded at a density of 20 million cells/mL in GelMA. Live/Dead and boron-dipyrromethene/4',6-diamidino-2-phenylindole (BODIPY/DAPI) staining of cells within the constructs demonstrated robust cell viability after 28 days in a growth (control) medium, and robust cell viability and lipid accumulation in adipogenic differentiation medium. qPCR gene expression analysis and protein analysis demonstrated an upregulated expression of key adipogenesis-associated genes. Overall, these data indicate that ASCs retain their adipogenic potential when seeded within GelMA hydrogels and cultured within perfusion bioreactors, and thus can be used in a 3D organ-on-a-chip system to study the role of the IPFP in the pathobiology of the knee OA.

  View details for DOI 10.3390/biom10071070

  View details for PubMedID 32709032

• Thermal Oxide Layer Enhances Crystallinity and Mechanical Properties for Plasma-Sprayed Hydroxyapatite Biomedical Coatings. ACS applied materials & interfaces Bose, S., Ke, D., Vu, A. A., Bandyopadhyay, A., Goodman, S. B. 2020

  Abstract

  The stability of plasma-sprayed hydroxyapatite (HA) coatings on metallic implants in vivo remains a significant challenge for load-bearing orthopedic implants despite their excellent mechanical and osteoconductive properties. This study focuses on oxide layer formation on the surface of Ti6Al4V samples through furnace heating at 600, 700, and 800 °C for 10 min for optimization of the most effective oxide layer to increase plasma coating crystallinity and improve plasma coating bond strength with the metal surface. The 800 °C heat treatment shows an effective oxide layer which increases coating crystallinity from 64 to 75% and coating adhesive bond strength from 25.9 ± 2.3 to 30.7 ± 1.1 MPa, while simultaneously reducing the dissolution rate of HA coatings. The addition of biologically relevant dopants, MgO and SiO2, show negligible effects on crystallinity and adhesive bond strength on plasma-sprayed HA coatings and additionally show an enhancement effect on osteoblast proliferation and differentiation. Moreover, the inclusion of these additivess shows an increase in osteogenesis in a rat distal femur model after 6 and 10 weeks of implantation. Overall, this study provides a direct solution to improve the crystallinity, adhesive bond strength, and osteogenic properties of plasma-sprayed HA coatings on orthopedic implants that is more manufacturable and translational from research to an industrial scale.

  View details for DOI 10.1021/acsami.0c05035

  View details for PubMedID 32530603

• Modulation of the Inflammatory Response and Bone Healing. Frontiers in endocrinology Maruyama, M., Rhee, C., Utsunomiya, T., Zhang, N., Ueno, M., Yao, Z., Goodman, S. B. 2020; 11: 386

  Abstract

  The optimal treatment for complex fractures and large bone defects is an important unsolved issue in orthopedics and related specialties. Approximately 5-10% of fractures fail to heal and develop non-unions. Bone healing can be characterized by three partially overlapping phases: the inflammatory phase, the repair phase, and the remodeling phase. Eventual healing is highly dependent on the initial inflammatory phase, which is affected by both the local and systemic responses to the injurious stimulus. Furthermore, immune cells and mesenchymal stromal cells (MSCs) participate in critical inter-cellular communication or crosstalk to modulate bone healing. Deficiencies in this inter-cellular exchange, inhibition of the natural processes of acute inflammation, and its resolution, or chronic inflammation due to a persistent adverse stimulus can lead to impaired fracture healing. Thus, an initial and optimal transient stage of acute inflammation is one of the key factors for successful, robust bone healing. Recent studies demonstrated the therapeutic potential of immunomodulation for bone healing by the preconditioning of MSCs to empower their immunosuppressive properties. Preconditioned MSCs (also known as "primed/ licensed/ activated" MSCs) are cultured first with pro-inflammatory cytokines (e.g., TNFα and IL17A) or exposed to hypoxic conditions to mimic the inflammatory environment prior to their intended application. Another approach of immunomodulation for bone healing is the resolution of inflammation with anti-inflammatory cytokines such as IL4, IL10, and IL13. In this review, we summarize the principles of inflammation and bone healing and provide an update on cellular interactions and immunomodulation for optimal bone healing.

  View details for DOI 10.3389/fendo.2020.00386

  View details for PubMedID 32655495

  View details for PubMedCentralID PMC7325942

• Modulation of the Inflammatory Response and Bone Healing FRONTIERS IN ENDOCRINOLOGY Maruyama, M., Rhee, C., Utsunomiya, T., Zhang, N., Ueno, M., Yao, Z., Goodman, S. B. 2020; 11

  View details for DOI 10.3389/fendo.2020.00386

  View details for Web of Science ID 000543904600001

• Recent Advances in Total Joint Replacement. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Goodman, S., Wimmer, M. A., Ploeg, H. 2020

  Abstract

  Joint Replacement (JR) is one of the most successful and cost-effective surgical procedures of all medical subspecialties. JR has been shown to reliably decrease pain and restore mobility and function in patients with end-stage arthritis. As the mean age of our general population continues to increase, so will the number of JRs worldwide. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24734

  View details for PubMedID 32410264

• Genetically modified il-4 over-expressing mscs enhance bone healing Ueno, M., Utsunomiya, T., Kohno, Y., Maruyama, M., Zhang, N., Lin, T. D., Yao, Z., Zwingenberger, S., Yang, F., Goodman, S. B. ELSEVIER SCI LTD. 2020: S178

  View details for Web of Science ID 000536174900406

• Injection of mscs mitigates particle associated chronic inflammation of bone Utsunomiya, T., Zhang, N., Lin, T. D., Kohno, Y., Ueno, M., Maruyama, M., Yao, Z., Goodman, S. B. ELSEVIER SCI LTD. 2020: S178–S179

  View details for Web of Science ID 000536174900407

• Macrophage Effects on Mesenchymal Stem Cell Osteogenesis in a Three-Dimensional in vitro Bone Model. Tissue engineering. Part A Romero-Lopez, M., Li, Z., Rhee, C., Maruyama, M., Pajarinen, J., O'Donnell, B., Lin, T., Lo, C., Hanlon, J., Dubowitz, R., Yao, Z., Bunnell, B. A., Lin, H., Tuan, R., Goodman, S. B. 2020

  Abstract

  As musculoskeletal disorders continue to increase globally, there is an increased need for novel, in vitro models to efficiently study human bone physiology in the context of both healthy and diseased conditions. For these models, the inclusion of innate immune cells is critical. Specifically, signaling factors generated from macrophages play key roles in the pathogenesis of many musculoskeletal processes and diseases, including fracture, osteoarthritis, infection, etc. In this study, we aim to engineer three-dimensional (3D) and macrophage-encapsulated bone tissues in vitro, to model cell behavior, signaling, and other biological activities in vivo, in comparison to current two-dimensional (2D) models. We first investigated and optimized 3D culture conditions for macrophages, and then co-cultured macrophages with mesenchymal stem cells (MSCs) which were induced to undergo osteogenic differentiation to examine the effect of macrophage on new bone formation. Seeded within a 3D hydrogel scaffold fabricated from photocrosslinked methacrylated gelatin, macrophages maintained high viability and were polarized toward an M1 or M2 phenotype. In co-cultures of macrophages and human MSCs, MSCs displayed immunomodulatory activities by suppressing M1 and enhancing M2 macrophage phenotypes. Lastly, addition of macrophages, regardless of polarization state, increased MSC osteogenic differentiation, compared to MSCs alone, with pro-inflammatory M1 macrophages enhancing new bone formation most effectively. In summary, this study illustrates the important roles that macrophage signaling and inflammation play in bone tissue formation.

  View details for DOI 10.1089/ten.TEA.2020.0041

  View details for PubMedID 32312178

• Nontraumatic Osteonecrosis of the Femoral Head: Where Do We Stand Today?: A 5-Year Update. The Journal of bone and joint surgery. American volume Mont, M. A., Salem, H. S., Piuzzi, N. S., Goodman, S. B., Jones, L. C. 2020

  View details for DOI 10.2106/JBJS.19.01271

  View details for PubMedID 32282421

• Selective screw fixation is associated with early failure of primary acetabular components for aseptic loosening. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Henry Goodnough, L., Bonano, J. C., Finlay, A. K., Aggarwal, V., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2020

  Abstract

  Selective augmentation of the acetabular component with screws during primary total hip arthroplasty (THA) assumes that the surgeon can detect when an acetabular component needs added stability. In contrast, non-selective screw users do not alter their practice based on their interpretation of stability and either use screws all or none of the time. We aimed to determine the effect of selective screw use on aseptic acetabular component loosening. We retrospectively reviewed aseptic failures of THA acetabular components. We compared the survivorship of selective to non-selective supplementation of acetabular fixation with screws, and compared time to revision, obesity and selective screw use. Selective screw use (n=16) was associated with earlier acetabular component aseptic loosening (median 1.9 years; interquartile range (IQR) 1.1-5.0) compared to non-selective screw use (n=22; median 5.6 years; IQR 2.0- 15.3, p = 0.010). Selective screw use was independently associated with earlier revision after adjusting for patient obesity. Obesity was associated with selective screw use in 50% of the cases versus 14% of non-selective cases (OR 6.3 CI 1.2-25.2, p = 0.028), possibly reflecting the increased difficulty in achieving acetabular component stability in this and other settings with compromised bone. Surgeons should carefully assess component stability at time of primary THA. If the acetabulum is not stable, the addition of screws alone may not be sufficient for acetabular component stability. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24649

  View details for PubMedID 32157712

• Reimbursement and Complications in Outpatient vs Inpatient Unicompartmental Arthroplasty. The Journal of arthroplasty Bosch, L. C., Bala, A., Denduluri, S. K., Maloney, W. J., Huddleston, J. I., Goodman, S. B., Amanatullah, D. F. 2020

  Abstract

  BACKGROUND: Increasing utilization of unicompartmental knee arthroplasty (UKA) has driven a greater push for outpatient treatment and cost containment in the setting of bundled payments. The purpose of this study is to evaluate utilization trends of inpatient vs outpatient UKA, index episode and 90-day reimbursement, and any differences in medical or surgical complications.METHODS: The PearlDiver database was employed to identify all inpatient and outpatient UKAs performed between 2007 and 2016 with 2-year follow-up. Patients were matched by age, gender, and Elixhauser Comorbidity Index. We tracked index procedure and global period reimbursement, 90-day medical and surgical complications, and 2-year surgical complications.RESULTS: The reimbursement and utilization cohort included 3181 outpatient and 5490 inpatient UKAs. Outpatient UKA and overall utilization of UKA increased over the study period. Mean index reimbursement of inpatient UKA was $2486.16 higher per procedure (P < .001) while mean global period reimbursement was $2782.13 higher per inpatient procedure (P < .001). Ninety-day medical complications including postoperative anemia (P < .001), transfusion (P= .024), and arrhythmia (P= .004) were more common with inpatient UKAs, whereas surgical wound complications (P= .001) and operative debridement (P= .028) were more common among outpatient UKAs. Outpatient UKA was not associated with an increased risk of periprosthetic joint infection (P > .05), aseptic loosening (P > .05), or revision surgery (P > .05) when compared to inpatient UKA.CONCLUSION: Outpatient UKA utilization is increasing and is associated with decreased reimbursement compared to inpatient UKA without increased risk of major medical complications, although it is associated with increased risk of wound complication and need for operative debridement at 90 days.

  View details for DOI 10.1016/j.arth.2020.02.063

  View details for PubMedID 32220483

• Increased NF-kappa B Activity in Osteoprogenitor-Lineage Cells Impairs the Balance of Bone Versus Fat in the Marrow of Skeletally Mature Mice REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE Lin, T., Pajarinen, J., Kohno, Y., Nabeshima, A., Lu, L., Nathan, K., Yao, Z., Wu, J. Y., Goodman, S. 2020; 6 (1): 69–77

  View details for DOI 10.1007/s40883-019-00112-7

  View details for Web of Science ID 000519367200007

• Increased NF-kB activity in osteoprogenitor-lineage cells impairs the balance of bone versus fat in the marrow of skeletally mature mice. Regenerative engineering and translational medicine Lin, T., Pajarinen, J., Kohno, Y., Nabeshima, A., Lu, L., Nathan, K., Yao, Z., Wu, J. Y., Goodman, S. 2020; 6: 69-77

  Abstract

  "Senile osteoporosis" is defined as significant aging-associated bone loss, and is accompanied by increased fat in the bone marrow. The proportion of adipocytes in bone marrow is inversely correlated with bone formation, and is associated with increased risk of fracture. NF-κB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-κB activity increases during aging; furthermore, constitutive activation of NF-κB significantly impairs skeletal development in neonatal mice. However, the effects of NF-κB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-κB activated transgenic mouse model (iNF-κB/OP) was generated to investigate the role of NF-κB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-κB/OP mice was only observed in the absence of doxycycline in vitro. Bone mineral density in the metaphyseal regions of femurs and tibias was reduced in iNF-κB/OP mice. No significant differences in bone volume fraction and cortical bone thickness were observed. Osmium-stained bone marrow fat was increased in epiphyseal and metaphyseal areas in the tibias of iNF-κB/OP mice. These findings suggest that targeting NF-κB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients.

  View details for DOI 10.1007/s40883-019-00112-7

  View details for PubMedID 32377560

  View details for PubMedCentralID PMC7202559

• Strontium enhances BMP-2 mediated bone regeneration in a femoral murine bone defect model JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Quade, M., Vater, C., Schlootz, S., Bolte, J., Langanke, R., Bretschneider, H., Gelinsky, M., Goodman, S. B., Zwingenberger, S. 2020; 108 (1): 174–82

  View details for DOI 10.1002/jbm.b.34376

  View details for Web of Science ID 000500822700018

• Knee or Spine Surgery First? A Survey of Treatment Order for Patients With Concurrent Degenerative Knee and Lumbar Spinal Disorders. The Journal of arthroplasty Goodman, S. B., Lachiewicz, P. F., Liu, N. n., Wood, K. B. 2020

  Abstract

  Total knee arthroplasty (TKA) and lumbar spine surgery have been reported to affect the outcomes of each other. There is insufficient evidence to guide the choice of treatment order for patients with both disorders that are equally symptomatic.Five clinical scenarios of concurrent, advanced, degenerative knee and lumbar spinal disorders were designed to survey surgeons' choices of treatment order and rationale. The spinal disorder was consistently degenerative lumbar spinal stenosis, but the knee conditions varied to include (1) osteoarthritis (OA) with varus deformity, (2) OA with valgus deformity, (3) rheumatoid arthritis with a severe flexion contracture, (4) OA without deformity, and (5) bilateral OA with windswept deformities. The survey was distributed to selected clinical members of the Knee Society and Scoliosis Research Society in North America. The surgeons' choices were compared among the 5 scenarios, and their comments were analyzed using text-mining.Responses were received from 42 of 74 (57%) knee arthroplasty surgeons and 55 of 100 (55%) spine surgeons. The percentages of knee arthroplasty surgeons recommending "TKA first" differed significantly among scenarios: 29%, 79%, 55%, 7%, and 81% for scenarios 1 through 5, respectively (P < .001). A similar pattern was noted for the spine surgeons.For patients with concurrent degenerative knee and lumbar spinal disorders, the severity and type of knee deformity influenced the preference of treatment order in both specialties. Severe valgus deformity and windswept deformities of the knee would drive the decision toward "TKA first."

  View details for DOI 10.1016/j.arth.2020.03.018

  View details for PubMedID 32247672

• Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version). Journal of orthopaedic translation Zhao, D. n., Zhang, F. n., Wang, B. n., Liu, B. n., Li, L. n., Kim, S. Y., Goodman, S. B., Hernigou, P. n., Cui, Q. n., Lineaweaver, W. C., Xu, J. n., Drescher, W. R., Qin, L. n. 2020; 21: 100–110

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a common and refractory disease in orthopaedic clinics. The number of patients with ONFH is increasing worldwide every year. There are an estimated 8.12 million patients with nontraumatic osteonecrosis in China alone. Treatment of nontraumatic osteonecrosis has always been a clinical challenge for orthopaedic surgeons. To further standardize diagnosis and treatment of ONFH, these guidelines provide not only basic diagnosis, treatment, and evaluation systems for ONFH but also expert advice and standards in many aspects, including epidemiology, aetiology, diagnostic criteria, pathological staging, prevention and treatment options, and postoperative rehabilitation. The aetiological factors of ONFH can currently be divided into two major categories: traumatic and nontraumatic; however, the specific pathological mechanism of ONFH is not completely clear. Currently, the staging system of ONFH formulated by the Association Research Circulation Osseous is widely used in clinical practice. Based on the changes in the intraosseous blood supply at different stages, the corresponding nonsurgical and surgical treatments are recommended, and when there are risk factors for possible ONFH, certain preventive measures to avoid the occurrence of osteonecrosis are recommended. These guidelines provide brief classification criteria and treatment regimen for osteonecrosis. Specification of the aetiology, treatment plan based on comprehensive consideration of the different stages of osteonecrosis, hip function, age, and occupation of the patients are important steps in diagnosis and developing treatment strategies.New advances in the epidemiology, etiology, pathophysiology, imaging, diagnosis and treatment of ONFH have been renewed in this revision. This guideline can be used for reference by orthopedic professionals and researchers, and for standardized diagnosis and treatment management under the clinical guidance, which is conducive to the prevention, treatment and further research of ONFH, improving the diagnosis and treatment level, making patients' symptoms under good control, and improving their quality of life.

  View details for DOI 10.1016/j.jot.2019.12.004

  View details for PubMedID 32309135

  View details for PubMedCentralID PMC7152793

• The routine use of synovial alpha-defensin is not necessary. The bone & joint journal Amanatullah, D. F., Cheng, R. Z., Huddleston Iii, J. I., Maloney, W. J., Finlay, A. K., Kappagoda, S. n., Suh, G. A., Goodman, S. B. 2020; 102-B (5): 593–99

  Abstract

  To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI).A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN).Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing.The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593-599.

  View details for DOI 10.1302/0301-620X.102B5.BJJ-2019-0473.R3

  View details for PubMedID 32349594

• Inflammation, Bone Healing and Osteonecrosis: From Bedside to Bench. Journal of inflammation research Goodman, S. B., Maruyama, M. 2020; 13: 913–23

  Abstract

  Osteonecrosis of the epiphyseal and metaphyseal regions of major weight-bearing bones of the extremities is a condition that is associated with local death of bone cells and marrow in the afflicted compartment. Chronic inflammation is a prominent feature of osteonecrosis. If the persistent inflammation is not resolved, this process will result in progressive collapse and subsequent degenerative arthritis. In the pre-collapse stage of osteonecrosis, attempt at joint preservation rather than joint replacement in this younger population with osteonecrosis is a major clinical objective. In this regard, core decompression, with/without local injection of bone marrow aspirate concentrate (BMAC), is an accepted and evidence-based method to help arrest the progression and improve the outcome of early-stage osteonecrosis. However, some patients do not respond favorably to this treatment. Thus, it is prudent to consider strategies to mitigate chronic inflammation concurrent with addressing the deficiencies in osteogenesis and vasculogenesis in order to save the affected joint. Interestingly, the processes of inflammation, osteonecrosis, and bone healing are highly inter-related. Therefore, modulating the biological processes and crosstalk among cells of the innate immune system, the mesenchymal stem cell-osteoblast lineage and others are important to providing the local microenvironment for resolution of inflammation and subsequent repair. This review summarizes the clinical and biologic principles associated with osteonecrosis and provides potential cutting-end strategies for modulating chronic inflammation and facilitating osteogenesis and vasculogenesis using local interventions. Although these studies are still in the preclinical stages, it is hoped that safe, efficacious, and cost-effective interventions will be developed to save the host's natural joint.

  View details for DOI 10.2147/JIR.S281941

  View details for PubMedID 33223846

• Interleukin-4 repairs wear particle induced osteolysis by modulating macrophage polarization and bone turnover. Journal of biomedical materials research. Part A Pajarinen, J. n., Lin, T. n., Nabeshima, A. n., Sato, T. n., Gibon, E. n., Jämsen, E. n., Khan, T. N., Yao, Z. n., Goodman, S. B. 2020

  Abstract

  Periprosthetic osteolysis remains as a major complication of total joint replacement surgery. Modulation of macrophage polarization with interleukin-4 (IL-4) has emerged as an effective means to limit wear particle-induced osteolysis. The aim of this study was to evaluate the efficacy of local IL-4 delivery in treating preexisting particle-induced osteolysis. To this end, recently established 8 week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4 weeks to induce osteolysis. IL-4 was then added to the particle infusion for another 4 weeks. This delayed IL-4 treatment (IL-4 Del) was compared to IL-4 delivered continuously (IL-4 Cont) with PE particles from the beginning and to the infusion of particles alone for 8 weeks. Both IL-4 treatments were highly effective in preventing and repairing preexisting particle-induced bone loss as assessed by μCT. Immunofluorescence indicated a significant reduction in the number of F4/80 + iNOS + M1 macrophages and increase in the number of F4/80 + CD206 + M2 macrophages with both IL-4 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL-4 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL-4 Del group than in the IL-4 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization.

  View details for DOI 10.1002/jbm.a.37142

  View details for PubMedID 33340244

• Preoperative Factors Associated with Remote Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: Post Hoc Analysis of a Perioperative Gabapentin Trial. Journal of pain research Hah, J. M., Hilmoe, H. n., Schmidt, P. n., McCue, R. n., Trafton, J. n., Clay, D. n., Sharifzadeh, Y. n., Ruchelli, G. n., Hernandez Boussard, T. n., Goodman, S. n., Huddleston, J. n., Maloney, W. J., Dirbas, F. M., Shrager, J. n., Costouros, J. G., Curtin, C. n., Mackey, S. C., Carroll, I. n. 2020; 13: 2959–70

  Abstract

  Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18-75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87-1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68-0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40-0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39-0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80-0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89-1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06-1.77; P=0.016).Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.

  View details for DOI 10.2147/JPR.S269370

  View details for PubMedID 33239904

  View details for PubMedCentralID PMC7680674

• IL-4 Overexpressing Mesenchymal Stem Cells within Gelatin-Based Microribbon Hydrogels Enhance Bone Healing in a Murine Long Bone Critical-size Defect Model. Journal of biomedical materials research. Part A Ueno, M. n., Lo, C. W., Barati, D. n., Conrad, B. n., Lin, T. n., Kohno, Y. n., Utsunomiya, T. n., Zhang, N. n., Maruyama, M. n., Rhee, C. n., Huang, E. n., Romero-Lopez, M. n., Tong, X. n., Yao, Z. n., Zwingenberger, S. n., Yang, F. n., Goodman, S. B. 2020

  Abstract

  Mesenchymal stem cell (MSC)-based therapy is a promising strategy for bone repair. Furthermore, the innate immune system, and specifically macrophages, play a crucial role in the differentiation and activation of MSCs. The anti-inflammatory cytokine IL-4 converts pro-inflammatory M1 macrophages into a tissue regenerative M2 phenotype, which enhances MSC differentiation and function. We developed lentivirus-transduced IL-4 over-expressing MSCs (IL-4 MSCs) that continuously produce IL-4 and polarize macrophages toward an M2 phenotype. In the current study, we investigated the potential of IL-4 MSCs delivered using a macroporous gelatin-based microribbon (μRB) scaffold for healing of critical size long bone defects in Mice. IL-4 MSCs within μRBs enhanced M2 marker expression without inhibiting M1 marker expression in the early phase, and increased macrophage migration into the scaffold. Six weeks after establishing the bone defect, IL-4 MSCs within μRBs enhanced bone formation and helped bridge the long bone defect. IL-4 MSCs delivered using macroporous μRB scaffold is potentially a valuable strategy for the treatment of critical size long bone defects. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.36982

  View details for PubMedID 32363683

• Inhibition of TET1 prevents the development of osteoarthritis and reveals the 5hmC landscape that orchestrates pathogenesis. Science translational medicine Smeriglio, P. n., Grandi, F. C., Davala, S. n., Masarapu, V. n., Indelli, P. F., Goodman, S. B., Bhutani, N. n. 2020; 12 (539)

  Abstract

  Osteoarthritis (OA) is a degenerative disease of the joint, which results in pain, loss of mobility, and, eventually, joint replacement. Currently, no disease-modifying drugs exist, partly because of the multiple levels at which cartilage homeostasis is disrupted. Recent studies have highlighted the importance of epigenetic dysregulation in OA, sparking interest in the epigenetic modulation for this disease. In our previous work, we characterized a fivefold increase in cytosine hydroxymethylation (5hmC), an oxidized derivative of cytosine methylation (5mC) associated with gene activation, accumulating at OA-associated genes. To test the role of 5hmC in OA, here, we used a mouse model of surgically induced OA and found that OA onset was accompanied by a gain of ~40,000 differentially hydroxymethylated sites before the notable histological appearance of disease. We demonstrated that ten-eleven-translocation enzyme 1 (TET1) mediates the 5hmC deposition because 98% of sites enriched for 5hmC in OA were lost in Tet1-/- mice. Loss of TET1-mediated 5hmC protected the Tet1-/- mice from OA development, including degeneration of the cartilage surface and osteophyte formation, by directly preventing the activation of multiple OA pathways. Loss of TET1 in human OA chondrocytes reduced the expression of the matrix metalloproteinases MMP3 and MMP13 and multiple inflammatory cytokines. Intra-articular injections of a dioxygenases inhibitor, 2-hydroxyglutarate, on mice after surgical induction of OA stalled disease progression. Treatment of human OA chondrocytes with the same inhibitor also phenocopied TET1 loss. Collectively, these data demonstrate that TET1-mediated 5hmC deposition regulates multiple OA pathways and can be modulated for therapeutic intervention.

  View details for DOI 10.1126/scitranslmed.aax2332

  View details for PubMedID 32295898

• Initial Presentation and Progression of Secondary Osteonecrosis of the Knee. The Journal of arthroplasty Boontanapibul, K. n., Steere, J. T., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2020

  Abstract

  Early detection and intervention are critical to maintaining the native articular cartilage before collapse in secondary osteonecrosis of the knee (SOK). We conducted a retrospective study documenting the initial stage of presentation and the progression of SOK.Our database was reviewed for patients younger than 65 years of age diagnosed with atraumatic SOK between 2002 and 2018. Demographic data, plain radiographs as well as MRI at initial evaluation, and initial treatment were classified and analyzed.One hundred four patients with 164 knees were identified. Mean age was 39 ± 16 years. Females (64%) with bilateral disease (58%) predominated. Seventy-five percent of patients had a history of corticosteroid use, of which 41% were diagnosed with hematologic malignancy and lupus. Fifteen percent of patients had a history of ethanol abuse. At initial presentation, 55% of patients were diagnosed with Ficat-Arlet stage I/II, while 45% were diagnosed with Ficat-Arlet stage III/IV. We found a significant difference in the mean age of patients at early stage of SOK with corticosteroid use (31 ± 12 years of age) when compared to ethanol use (43 ± 13 years of age, P = .02). Treatments included observation (57%), joint preservation surgery (20%), and total knee arthroplasty (23%).Nearly half of patients presented at late stage compromising the potential for joint preservation. The difference in age of referral by over a decade, based on etiology of SOK, suggests a strong provider-based referral or screening bias may be present. Hence, a multidisciplinary approach to earlier detection and referral may be a more effective strategy for preventing the progression of SOK.

  View details for DOI 10.1016/j.arth.2020.05.020

  View details for PubMedID 32527695

• Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage Science Advances Grandi, F. ., Baskar, R., Smeriglio, P., Murkherjee, S., Indelli, P., F. Amanatullah, D., Goodman, S., Chu, C., Bendall , S., Bhutani, N. 2020; 6 (11)

  View details for DOI 10.1126/sciadv.aay5352

• Tumor Necrosis Factor Primes and Metal Particles Activate the NLRP3 Inflammasome in Human Primary Macrophages. Acta biomaterialia Jämsen, E. n., Pajarinen, J. n., Kouri, V. P., Rahikkala, A. n., Goodman, S. B., Manninen, M. n., Nordström, D. C., Eklund, K. K., Nurmi, K. n. 2020

  Abstract

  Aseptic loosening of total joint replacements is driven by a macrophage-mediated inflammatory reaction to implant-derived wear particles. Phagocytosis of implant debris has been suggested to activate the NLRP3 inflammasome leading to secretion of interleukin (IL)-1β. However, factors and molecular mechanisms driving the particle-induced inflammasome activation are yet to be fully elucidated. In this study, we investigated the inflammasome response of human primary macrophages to titanium, chromium, and molybdenum particles in vitro. We observed that particles alone were not sufficient to induce IL-1β secretion, but an additional priming signal-such as bacterial lipopolysaccharide (LPS)-was required to license the inflammasome activation. By using specific inhibitors against the inflammasome signaling pathway, we demonstrate that the particle-induced IL-1β secretion depended upon activation of the NLRP3 inflammasome. We further hypothesized that tumor necrosis factor (TNF) could substitute for LPS as a priming signal, and found that particle stimulation together with preceding TNF treatment resulted in inflammasome-dependent IL-1β production as well. Our results show that the NLRP3 inflammasome mediates wear particle responses in human primary macrophages, and its activation does not necessarily require the presence of bacterial components, but can be induced under aseptic conditions by TNF priming. Statement of Significance This study was conducted to elucidate the molecular mechanisms of metal particle-induced IL-1β secretion in human primary macrophages. Production of this pro-inflammatory mediator from wear particle-activated macrophages has been associated with increased bone loss around total joint replacements-a condition eventually requiring revision surgery. Our results confirm that together with a co-stimulatory priming signal, particles of common implant metals elicit macrophage-mediated IL-1β secretion through activation of the NLRP3 inflammasome pathway. We also present a concept of TNF priming in this context, demonstrating that the particle-related IL-1β secretion can take place in a truly sterile environment. Thus, inhibition of inflammasome signaling appears a means to prevent wear particle-induced inflammation and development of peri-prosthetic osteolysis.

  View details for DOI 10.1016/j.actbio.2020.03.017

  View details for PubMedID 32194260

• Reply to Letter to the Editor on "Mental Health Status Improves Following Total Knee Arthroplasty". The Journal of arthroplasty Horst, P. K., Barrett, A. A., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2020

  View details for DOI 10.1016/j.arth.2020.05.067

  View details for PubMedID 32571590

• Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches. Frontiers in bioengineering and biotechnology Goodman, S. B., Lin, T. n. 2020; 8: 641

  Abstract

  Healing of fractures and bone defects normally follows an orderly series of events including formation of a hematoma and an initial stage of inflammation, development of soft callus, formation of hard callus, and finally the stage of bone remodeling. In cases of severe musculoskeletal injury due to trauma, infection, irradiation and other adverse stimuli, deficient healing may lead to delayed or non-union; this results in a residual bone defect with instability, pain and loss of function. Modern methods of mechanical stabilization and autologous bone grafting are often successful in achieving fracture union and healing of bone defects; however, in some cases, this treatment is unsuccessful because of inadequate biological factors. Specifically, the systemic and local microenvironment may not be conducive to bone healing because of a loss of the progenitor cell population for bone and vascular lineage cells. Autologous bone grafting can provide the necessary scaffold, progenitor and differentiated lineage cells, and biological cues for bone reconstruction, however, autologous bone graft may be limited in quantity or quality. These unfavorable circumstances are magnified in systemic conditions with chronic inflammation, including obesity, diabetes, chronic renal disease, aging and others. Recently, strategies have been devised to both mitigate the necessity for, and complications from, open procedures for harvesting of autologous bone by using minimally invasive aspiration techniques and concentration of iliac crest bone cells, followed by local injection into the defect site. More elaborate strategies (not yet approved by the U.S. Food and Drug Administration-FDA) include isolation and expansion of subpopulations of the harvested cells, preconditioning of these cells or inserting specific genes to modulate or facilitate bone healing. We review the literature pertinent to the subject of modifying autologous harvested cells including MSCs to facilitate bone healing. Although many of these techniques and technologies are still in the preclinical stage and not yet approved for use in humans by the FDA, novel approaches to accelerate bone healing by modifying cells has great potential to mitigate the physical, economic and social burden of non-healing fractures and bone defects.

  View details for DOI 10.3389/fbioe.2020.00641

  View details for PubMedID 32671040

  View details for PubMedCentralID PMC7328340

• Outcomes of Cemented Total Knee Arthroplasty for Secondary Osteonecrosis of the Knee. The Journal of arthroplasty Boontanapibul, K. n., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2020

  Abstract

  Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of contemporary cemented bicompartmental TKA with/without patellar resurfacing for SOK.Thirty-eight cemented TKAs in 27 patients with atraumatic SOK, mean age 43 years (17 to 65), were retrospectively reviewed. Seventy-four percent had a history of corticosteroid use, and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), and all were asymptomatic without joint collapse. The mean followup was 7 years (2 to 12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2 to 3 years.Ninety-two percent had implant survivorship free from revision with significant improvement in KSS. Causes of revision included aseptic tibial loosening (one), deep infection (one), and instability with patellofemoral issues (one). Four of six cases also with patellar osteonecrosis received resurfacing, including one with periprosthetic patellar fracture after minor trauma, with satisfactory clinical results after conservative treatment. None of the unrevised knees had progressive radiolucent lines or evidence of loosening. An unresurfaced patella, use of a stem extension or a varus-valgus constrained prosthesis constituted 18%, 8% and 3%, respectively.Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation.

  View details for DOI 10.1016/j.arth.2020.08.061

  View details for PubMedID 33011011

• Diagnosis of Osteonecrosis of the Femoral Head: Too Little, Too Late, and Independent of Etiology. The Journal of arthroplasty Boontanapibul, K. n., Steere, J. T., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2020

  Abstract

  Joint preservation is more effective in early-stage osteonecrosis of the femoral head (ONFH); thus, prompt diagnosis when the femoral head is still salvageable is important. We report a 20-year retrospective study that summarizes age at presentation, etiology, and Association Research Circulation Osseous stage at diagnosis.Our database was reviewed to identify patients younger than 65 years of age who were diagnosed with atraumatic ONFH between 1998 and 2018. Demographic characteristics of patients were evaluated and categorized into different subgroups.Four hundred thirteen patients were identified. At initial presentation, 23% were diagnosed with early-stage ONFH, while 77% were diagnosed with late-stage ONFH. Forty-nine percent had a history of corticosteroid use, of which 13% were diagnosed with hematologic malignancy and 8% were diagnosed with lupus. Ethanol abuse, idiopathic, sickle cell disease, and human immunodeficiency virus were present in 11%, 30%, 3%, and 3%, respectively. The mean age of patients with corticosteroid use (40 ± 14 years) was significantly younger than ethanol use (46 ± 11 years, P = .014) and idiopathic causes (48 ± 11 years, P < .001), but significantly older than sickle cell disease (32 ± 11 years, P = .031). There was no difference in the age of presentation for early-stage and late-stage ONFH by etiology.Nearly 80% of the patients presented with late-stage ONFH. Hence, we have a narrow window of opportunity for hip preservation surgery before femoral head collapse. A multidisciplinary approach to improve screening awareness for early detection by focusing on the etiologic identification and patient education might reduce the incidence of hip arthroplasty in young patients.

  View details for DOI 10.1016/j.arth.2020.04.092

  View details for PubMedID 32456965

• The efficacy of core decompression for steroidassociated osteonecrosisof the femoral head in rabbits. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Maruyama, M. n., Lin, T. n., Kaminow, N. I., Thio, T. n., Storaci, H. W., Pan, C. C., Yao, Z. n., Takagi, M. n., Goodman, S. B., Yang, Y. P. 2020

  Abstract

  Although core decompression (CD) is often performed in the early stages of osteonecrosis of the femoral head (ONFH), the procedure does not always prevent subsequent deterioration and the effects of CD are not fully clarified.The aim of this study was to evaluate the efficacy of CD for steroid associated ONFH in rabbits.Twelve male and twelve female New Zealand rabbits were injected intramuscularly 20 mg/kg of methylprednisolone once and were divided into the disease control and CD groups. In the disease control group, rabbits had no treatment and were euthanized at 12 weeks post-injection. In the CD group, rabbits underwent left femoral CD at 4 weeks post-injection and were euthanized 8 weeks postoperatively. The left femurs were collected to perform morphological, biomechanical and histological analysis.Bone mineral density and bone volume fraction in the femoral head in the CD group were significantly higher than in the disease control group. However, no difference in the mechanical strength was observed between the two groups. Histological analysis showed thatalkaline phosphatase and CD31 positive cells significantly increased in the males after CD treatment. The number of empty lacunae in the surrounding trabecular bone was significantly higher in the CD group.The current study indicated that CD improved the morphological properties, but did not improve the mechanical strength in the femoral headat early stage ONFH.These data suggest the need for additional biological, mechanical strategies,and therapeutic windows to improve the outcome of early stage steroid associated ONFH. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24888

  View details for PubMedID 33095462

• Osteochondral Tissue Chip Derived From iPSCs: Modeling OA Pathologies and Testing Drugs FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY Lin, Z., Li, Z., Li, E. N., Li, X., Del Duke, C. J., Shen, H., Hao, T., Bunnell, B. A., Goodman, S. B., Alexander, P. G., Tuan, R. S., Lin, H. 2019; 7

  View details for DOI 10.3389/fbioe.2019.00411

  View details for Web of Science ID 000504972600001

• Osteochondral Tissue Chip Derived From iPSCs: Modeling OA Pathologies and Testing Drugs. Frontiers in bioengineering and biotechnology Lin, Z., Li, Z., Li, E. N., Li, X., Del Duke, C. J., Shen, H., Hao, T., O'Donnell, B., Bunnell, B. A., Goodman, S. B., Alexander, P. G., Tuan, R. S., Lin, H. 2019; 7: 411

  Abstract

  Osteoarthritis (OA) is a chronic disease mainly characterized by degenerative changes in cartilage, but other joint elements such as bone are also affected. To date, there are no disease-modifying OA drugs (DMOADs), owing in part to a deficiency of current models in simulating OA pathologies and etiologies in humans. In this study, we aimed to develop microphysiological osteochondral (OC) tissue chips derived from human induced pluripotent stem cells (iPSCs) to model the pathologies of OA. We first induced iPSCs into mesenchymal progenitor cells (iMPCs) and optimized the chondro- and osteo-inductive conditions for iMPCs. Then iMPCs were encapsulated into photocrosslinked gelatin scaffolds and cultured within a dual-flow bioreactor, in which the top stream was chondrogenic medium and the bottom stream was osteogenic medium. After 28 days of differentiation, OC tissue chips were successfully generated and phenotypes were confirmed by real time RT-PCR and histology. To create an OA model, interleukin-1β (IL-1β) was used to challenge the cartilage component for 7 days. While under control conditions, the bone tissue promoted chondrogenesis and suppressed chondrocyte terminal differentiation of the overlying chondral tissue. Under conditions modeling OA, the bone tissue accelerated the degradation of chondral tissue which is likely via the production of catabolic and inflammatory cytokines. These findings suggest active functional crosstalk between the bone and cartilage tissue components in the OC tissue chip under both normal and pathologic conditions. Finally, a selective COX-2 inhibitor commonly prescribed drug for OA, Celecoxib, was shown to downregulate the expression of catabolic and proinflammatory cytokines in the OA model, demonstrating the utility of the OC tissue chip model for drug screening. In summary, the iPSC-derived OC tissue chip developed in this study represents a high-throughput platform applicable for modeling OA and for the screening and testing of candidate DMOADs.

  View details for DOI 10.3389/fbioe.2019.00411

  View details for PubMedID 31921815

  View details for PubMedCentralID PMC6930794

• The 2019 Revised Version of Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head. The Journal of arthroplasty Yoon, B., Mont, M. A., Koo, K., Chen, C., Cheng, E. Y., Cui, Q., Drescher, W., Gangji, V., Goodman, S. B., Ha, Y., Hernigou, P., Hungerford, M. W., Iorio, R., Jo, W., Jones, L. C., Khanduja, V., Kim, H. K., Kim, S., Kim, T., Lee, H. Y., Lee, M. S., Lee, Y., Lee, Y. J., Nakamura, J., Parvizi, J., Sakai, T., Sugano, N., Takao, M., Yamamoto, T., Zhao, D. 2019

  Abstract

  BACKGROUND: The Association Research Circulation Osseous (ARCO) presents the 2019 revised staging system of osteonecrosis of the femoral head (ONFH) based on the 1994 ARCO classification.METHODS: In October 2018, ARCO established a task force to revise the staging system of ONFH. The task force involved 29 experts who used a web-based survey for international collaboration. Content validity ratios for each answer were calculated to identify the levels of agreement. For the rating queries, a consensus was defined when more than 70% of the panel members scored a 4 or 5 rating on a 5-point scale.RESULTS: Response rates were 93.1%-100%, and through the 4-round Delphi study, the 1994 ARCO classification for ONFH was successfully revised. The final consensus resulted in the following 4-staged system: stage I-X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II-X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III-fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV-X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. This revised staging system does not incorporate the previous subclassification or quantitation parameters, but the panels agreed on the future development of a separate grading system for predicting disease progression.CONCLUSION: A staging system has been developed to revise the 1994 ARCO classification for ONFH by an expert panel-based Delphi survey. ARCO approved and recommends this revised system as a universal staging of ONFH.

  View details for DOI 10.1016/j.arth.2019.11.029

  View details for PubMedID 31866252

• Guest Editorial: The Current Use of Biologics and Cellular Therapies in Orthopaedics: Are We Going Down the Right Path? Clinical orthopaedics and related research Manner, P. A., Goodman, S. B. 2019

  View details for DOI 10.1097/CORR.0000000000001068

  View details for PubMedID 31764317

• Statin use is associated with less postoperative cardiac arrhythmia after total hip arthroplasty HIP INTERNATIONAL Chen, M. J., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Aaronson, A. J., Amanatullah, D. F. 2019; 29 (6): 618–23

  View details for DOI 10.1177/1120700018816091

  View details for Web of Science ID 000487029700010

• Osteogenic ability of rat bone marrow concentrate is at least as efficacious as mesenchymal stem cells in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Kohno, Y., Lin, T., Pajarinen, J., Romero-Lopez, M., Maruyama, M., Huang, J., Nathan, K., Yao, Z., Goodman, S. B. 2019; 107 (8): 2500–2506

  View details for DOI 10.1002/jbm.b.34340

  View details for Web of Science ID 000488626300005

• Response to Letter to the Editor on "Total Knee Arthroplasty Has Positive Effect on Patients With Low Mental Health Scores". The Journal of arthroplasty Horst, P. K., Barrett, A. A., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2019

  View details for DOI 10.1016/j.arth.2019.10.047

  View details for PubMedID 31785963

• Inflammation and Bone Repair: From Particle Disease to Tissue Regeneration. Frontiers in bioengineering and biotechnology Goodman, S. B., Pajarinen, J., Yao, Z., Lin, T. 2019; 7: 230

  Abstract

  When presented with an adverse stimulus, organisms evoke an immediate, pre-programmed, non-specific innate immune response. The purpose of this reaction is to maintain the organism's biological integrity and function, mitigate or eradicate the injurious source, and re-establish tissue homeostasis. The initial stage of this protective reaction is acute inflammation, which normally reduces or terminates the offending stimulus. As the inflammatory reaction recedes, the stage of tissue repair and regeneration follows. If the above sequence of events is perturbed, reconstitution of normal biological form and function will not be achieved. Dysregulation of these activities may result in incomplete healing, fibrosis, or chronic inflammation. Our laboratory has studied the reaction to wear particles from joint replacements as a paradigm for understanding the biological pathways of acute and chronic inflammation, and potential translational treatments to reconstitute lost bone. As inflammation is the cornerstone for healing in all anatomical locations, the concepts developed have relevance to tissue engineering and regenerative medicine in all organ systems. To accomplish our goal, we developed novel in vitro and in vivo models (including the murine femoral continuous intramedullary particle infusion model), translational strategies including modulation of macrophage chemotaxis and polarization, and methods to interfere with key transcription factors NFκB and MyD88. We purposefully modified MSCs to facilitate bone healing in inflammatory scenarios: by preconditioning the MSCs, and by genetically modifying MSCs to first sense NFκB activation and then overexpress the anti-inflammatory pro-regenerative cytokine IL-4. These advancements provide significant translational opportunities to enhance healing in bone and other organs.

  View details for DOI 10.3389/fbioe.2019.00230

  View details for PubMedID 31608274

  View details for PubMedCentralID PMC6761220

• Inflammation and Bone Repair: From Particle Disease to Tissue Regeneration FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY Goodman, S. B., Pajarinen, J., Yao, Z., Lin, T. 2019; 7

  View details for DOI 10.3389/fbioe.2019.00230

  View details for Web of Science ID 000487523100001

• Cell-Based and Scaffold-Based Therapies for Joint Preservation in Early-Stage Osteonecrosis of the Femoral Head: A Review of Basic Research. JBJS reviews Maruyama, M., Lin, T., Pan, C., Moeinzadeh, S., Takagi, M., Yang, Y. P., Goodman, S. B. 2019

  View details for DOI 10.2106/JBJS.RVW.18.00202

  View details for PubMedID 31503099

• Effect of Aging on the Macrophage Response to Titanium Particles. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Jamsen, E., Pajarinen, J., Lin, T., Lo, C., Nabeshima, A., Lu, L., Nathan, K., Eklund, K. K., Yao, Z., Goodman, S. B. 2019

  Abstract

  Macrophage-mediated inflammatory reaction to implant wear particles drives bone loss around total joint replacements (TJR). Although most TJR recipients are elderly, studies linking wear particle-activated macrophages and peri-implant osteolysis have not taken into account the multiple effects that aging has on the innate immune system and, in particular, on macrophages. To address this, we compared the wear particle responses of bone marrow macrophages obtained from young (2-month) and aged (18-month) mice. Macrophages were polarized to M0, M1, or M2 phenotypes in vitro, challenged with titanium particles, and their inflammatory response was characterized at multiple time points by qRT-PCR and ELISA. In addition, age-dependent changes in activation of transcription factor NF-kappaB were analyzed by a lentiviral vector-based luciferase reporter system. The particle stimulation experiment was further repeated using human primary macrophages isolated from blood donors of different ages. We found that the pro-inflammatory responses were generally higher in macrophages obtained from young mice, but differences between the age groups remained small and of uncertain biological significance. Noteworthily, M2 polarization effectively suppressed the particle-induced inflammation in both young and aged macrophages. These results suggest that aging of the innate immune system per se plays no significant role in the response of macrophages to titanium particles, whereas induction of M2 polarization appears a promising strategy to limit macrophage-mediated inflammation regardless of age. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24461

  View details for PubMedID 31498470

• Total Knee Arthroplasty Has A Positive Effect on Patients With Low Mental Health Scores. The Journal of arthroplasty Horst, P. K., Barrett, A. A., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2019

  Abstract

  BACKGROUND: The purpose of this study is to determine the impact of total knee arthroplasty (TKA) on mental health.METHODS: A total of 205 patients who underwent primary TKA with baseline and 1-year postoperative Short Form-12 Mental Component Score (MCS) were included in this retrospective analysis. Eighty-five (41%) patients had a preoperative MCS less than 50 points, while 120 (59%) patients had a preoperative MCS over 50 points. Two groups were assigned to the patients based on their preoperative MCS: low MCS <50 and high MCS >50.RESULTS: A preoperative MCS less than 50 points was predictive of greater improvement in MCS at 1 year after TKA (P < .001). Patients with low MCS improved by a mean of 10.6 points from 39.1 ± 8.6 points preoperatively to mean of 49.7 ± 10.7 points 1 year after TKA (P < .001). Patients with a high MCS decreased by a mean of 3.5 points from 60.01 ± 6.0 points preoperatively to mean of 56.6 ± 6.8 points 1 year after TKA (P < .001). This remained higher than the postoperative MCS of the patients with a low MCS, 49.7 ± 10.7 (P < .001). The patients with a high MCS had greater improvement in the Short Form-12-Physical domain (14.8 points) than the patients with a low MCS (9.2 points, P < .001).CONCLUSION: Patients with lower baseline mental health had greater improvement in postoperative mental health following TKA than patients with higher baseline mental health. Low preoperative MCS was associated with less improvement in patient-reported outcome measures. Patients with lower baseline mental health scores before TKA benefit mentally and physically from the procedure.

  View details for DOI 10.1016/j.arth.2019.08.033

  View details for PubMedID 31522853

• Treating Titanium Particle-Induced Inflammation with Genetically Modified NF-κB Sensing IL-4 Secreting or Preconditioned Mesenchymal Stem Cells in Vitro. ACS biomaterials science & engineering Kohno, Y., Lin, T., Pajarinen, J., Jämsen, E., Romero-Lopez, M., Maruyama, M., Lo, C. W., Ueno, M., Nathan, K., Yao, Z., Goodman, S. B. 2019; 5 (6): 3032-3038

  Abstract

  Titanium and titanium-based alloys are widely used in orthopaedic implants. Total joint replacement is very successful; however, the foreign body response and chronic inflammation caused by implant-derived biomaterial debris still remain as unsolved issues. Aseptic loosening accompanied by wear debris-induced osteolysis (bone loss) is one of the most frequent causes for late failure and revision surgery. Mesenchymal stem cells (MSCs) and IL-4 may be possible treatment strategies because of their immunomodulatory properties. We investigated the efficacy of novel MSC-based treatments on immunomodulation and osteogenic differentiation in an innovative cell coculture model of titanium particle-induced inflammation in the periprosthetic tissues. MSCs and macrophages were collected from the bone marrow of Balb/c mice. Both MSCs and macrophages (representing endogenous cells at the periprosthetic tissue) were seeded on the bottom wells of the 24-well transwell plates. We generated genetically modified NF-κB sensing IL-4 secreting MSCs (inflammatory responsive MSCs) and MSCs preconditioned by lipopolysaccharide and TNF-α to further enhance their immunomodulatory function. These modified MSCs (representing exogenous therapeutic cells implanted to the periprosthetic tissue) were seeded on the upper chambers of the transwell plates. These cocultures were then exposed to titanium particles for 7 days. NF-κB sensing IL-4 secreting MSCs showed strong immunomodulation (significantly reduced TNF-α and induced Arg1 expression) and promoted early osteogenesis (significantly induced Runx2, ALP, and β-catenin as well as reduced Smurf2 expression) at day 7. IL-4 secreting MSCs also decreased TNF-α protein secretion as early as day 3 and increased IL-1ra protein secretion at day 7, suggesting efficacious immunomodulation of particle-induced inflammation. Preconditioned MSCs did not show significant immunomodulation in this short-term experiment, but ALP and β-catenin expression were significantly induced at day 7. Our results suggest that genetically modified IL-4 secreting MSCs and preconditioned MSCs have the potential to optimize bone regeneration in inflammatory conditions including periprosthetic osteolysis.

  View details for DOI 10.1021/acsbiomaterials.9b00560

  View details for PubMedID 32391436

  View details for PubMedCentralID PMC7207059

• Treating Titanium Particle-Induced Inflammation with Genetically Modified NF-kappa B Sensing IL-4 Secreting or Preconditioned Mesenchymal Stem Cells in Vitro ACS BIOMATERIALS SCIENCE & ENGINEERING Kohno, Y., Lin, T., Pajarinen, J., Jamsen, E., Romero-Lopez, M., Maruyama, M., Lo, C., Ueno, M., Nathan, K., Yao, Z., Goodman, S. B. 2019; 5 (6): 3032–38

  View details for DOI 10.1021/acsbiomaterials.9b00560

  View details for Web of Science ID 000471212300033

• American Association of Hip and Knee Surgeons, Hip Society, and Knee Society Position Statement on Biologics for Advanced Hip and Knee Arthritis JOURNAL OF ARTHROPLASTY Browne, J. A., Nho, S. J., Goodman, S. B., Della Valle, C. J. 2019; 34 (6): 1051–52

  Abstract

  Pigmented villonodular synovitis (PVNS) is a locally destructive histiocytic proliferation most commonly occurring in the knee. Extensive local joint destruction can indicate the need for a total knee arthroplasty (TKA). The objective of this study is to evaluate PVNS of the knee as a risk factor for complication after TKA.Patients who underwent TKA with a diagnosis of PVNS of the knee from 2007 to 2016 were identified in a national private payer insurance database. Complication rates for emergency room visits, readmission, revision, stiffness, infection, and death were calculated and compared to a control population of patients who received TKA for osteoarthritis (OA).Four hundred fifty-three patients were diagnosed with PVNS of the knee and underwent TKA during the time period and compared with a matched control cohort of 1812 patients who underwent TKA for OA. The rate of revision TKA at 2 years, emergency room visits, readmission, and death did not differ between the PVNS group and the control cohort. The PVNS group had stiffness at 1 year compared to the OA group (6.84% vs 4.69%, odds ratio 1.48, P = .023). The infection rate at 2 years was 3.31% in the PVNS group and 1.55% in the OA group (odds ratio 1.73, P = .011).The complication rates for TKA in patients with a diagnosis of PVNS of the knee have not been previously demonstrated. These patients have a higher rate of stiffness and infection when compared to a control cohort, so they may have a more complicated postoperative course.

  View details for DOI 10.1016/j.arth.2019.03.068

  View details for Web of Science ID 000468307600002

  View details for PubMedID 30266323

• CORR Insights: How Does Mortality Risk Change Over Time After Hip and Knee Arthroplasty? Clinical orthopaedics and related research Goodman, S. B. 2019; 477 (6): 1422–23

  View details for DOI 10.1097/CORR.0000000000000724

  View details for PubMedID 31136445

• Stem Cells and Platelet-Rich Plasma Injections for Advanced Hip and Knee Arthritis: Enthusiasm Outpaces Science JOURNAL OF ARTHROPLASTY Browne, J. A., Nho, S. J., Goodman, S. B., Callaghan, J. J., Della Valle, C. J. 2019; 34 (6): 1049–50

  View details for DOI 10.1016/j.arth.2019.03.074

  View details for Web of Science ID 000468307600001

• Improved Range of Motion and Patient-Reported Outcome Scores With Fixed-Bearing Revision Total Knee Arthroplasty for Suboptimal Axial Implant Rotation JOURNAL OF ARTHROPLASTY Amanatullah, D. E., Lichstein, P. M., Lundergan, W. G., Wong, W. W., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2019; 34 (6): 1174–78

  View details for DOI 10.1016/j.arth.2019.02.007

  View details for Web of Science ID 000468307600024

• Hip or spine surgery first? A SURVEY OF TREATMENT ORDER FOR PATIENTS WITH CONCURRENT DEGENERATIVE HIP AND SPINAL DISORDERS Liu, N., Goodman, S. B., Lachiewicz, P. F., Wood, K. B. BRITISH EDITORIAL SOC BONE JOINT SURGERY. 2019: 37–44

  View details for Web of Science ID 000469965700007

• Two-step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy JOURNAL OF ORTHOPAEDIC RESEARCH Bolte, J., Vater, C., Culla, A., Ahlfeld, T., Nowotny, J., Kasten, P., Disch, A. C., Goodman, S. B., Gelinsky, M., Stiehler, M., Zwingenberger, S. 2019; 37 (6): 1318–28

  View details for DOI 10.1002/jor.24215

  View details for Web of Science ID 000470781400014

• Computer Navigation vs Conventional Total Hip Arthroplasty: AMedicare Database Analysis. The Journal of arthroplasty Montgomery, B. K., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2019

  Abstract

  BACKGROUND: Computer-assisted surgery (CAS) is applied to total hip arthroplasty (THA) in an attempt to optimize implant positioning. The effect of CAS on postoperative complications after THA remains unknown. Our study aims to assess the change in complication rates when CAS is used in THA.METHODS: The Medicare database was studied from 2005 to 2012. All THAs performed with CAS were identified. A total of 64,944 THAs were identified, including 5412 CAS-THAs and 59,532 conventional THAs. Medical and surgical adverse events were collected at various time points.RESULTS: CAS-THA was not associated with a decreased rate of dislocation at 30 days (1.0% vs 1.2%; odds ratio [OR], 1.14; P= .310), 90 days (1.1% vs 1.4%; OR, 1.23; P= .090), or 2 years (2.3% vs 2.3%; OR, 1.01; P= .931). CAS-THA was associated with a significantly higher rate of periprosthetic fracture at 30 days (0.4% vs 0.6%; OR, 1.46; P= .040) as well as revision THA at 30 days (1.0% vs 1.4%; OR, 1.43; P= .003) and 90 days (1.2% vs 1.7%; OR, 1.42; P < .002) when compared to conventional THA. CAS-THA was associated with a significantly lower rate of deep vein thrombosis and pulmonary embolism when compared to conventional THA at all time points (P < .05).CONCLUSION: Administrative coding data fail to demonstrate any clinically significant reduction in short-term adverse events with CAS-THA. Further study is warranted to evaluate whether the purported benefits of CAS result in a reduction of the adverse events after THA.

  View details for DOI 10.1016/j.arth.2019.04.063

  View details for PubMedID 31176561

• IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis ELIFE Wang, Q., Lepus, C. M., Raghu, H., Reber, L. L., Tsai, M. M., Wong, H. H., von Kaeppler, E., Lingampalli, N., Bloom, M. S., Hu, N., Elliott, E. E., Oliviero, F., Punzi, L., Giori, N. J., Goodman, S. B., Chu, C. R., Sokolove, J., Fukuoka, Y., Schwartz, L. B., Galli, S. J., Robinson, W. H. 2019; 8

  View details for DOI 10.7554/eLife.39905

  View details for Web of Science ID 000467895900001

• Bone Regeneration by Controlled Release of Bone Morphogenetic Protein-2: A Rabbit Spinal Fusion Chamber Molecular Study TISSUE ENGINEERING PART A Hu, T., Naidu, M., Yang, Z., Lam, W., Kumarsing, R., Ren, X., Ng, F., Wang, M., Liu, L., Tan, K., Kwok, K., Goodman, S. B., Goh, J., Wong, H. 2019

  View details for DOI 10.1089/ten.tea.2018.0281

  View details for Web of Science ID 000466514000001

• Venous thromboprophylaxis after total hip arthroplasty: aspirin, warfarin, enoxaparin, or factor Xa inhibitors? Hip international : the journal of clinical and experimental research on hip pathology and therapy Bala, A., Murasko, M. J., Burk, D. R., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2019: 1120700019841600

  Abstract

  INTRODUCTION: Debate over the ideal agent for venous thromboembolism (VTE) prophylaxis after total hip arthroplasty (THA) has led to changes in prescribing trends of commonly used agents. We investigate variation in utilisation and the differences in VTE incidence and bleeding risk in primary THA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors.METHODS: 8829 patients were age/sex matched from a large database of primary THAs performed between 2007 and 2016. Utilisation was calculated using compound annual growth rate. Incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications, postoperative anaemia, and transfusion were identified at 2weeks, 30days, 6weeks, and 90days.RESULTS: Aspirin use increased by 33%, enoxaparin by 7%, and factor Xa inhibitors by 31%. Warfarin use decreased by 1%. Factor Xa inhibitors (1.7%) and aspirin (1.7%) had the lowest incidence of DVT followed by enoxaparin (2.6%), and warfarin (3.7%) at 90days. Factor Xa inhibitors (12%) and aspirin (12%) had the lowest incidence of blood transfusion followed by warfarin (15%) and enoxaparin (17%) at 90 days. There was no difference in incidence of blood transfusion or bleeding-related complications nor any detectable difference in symptomatic PE incidence.CONCLUSIONS: The utilisation of aspirin and factor Xa inhibitors increased over time. Aspirin and factor Xa inhibitors provided improved DVT prophylaxis with lower rates of postoperative anaemia compared to enoxaparin and warfarin.

  View details for DOI 10.1177/1120700019841600

  View details for PubMedID 30990095

• Strontium enhances BMP-2 mediated bone regeneration in a femoral murine bone defect model. Journal of biomedical materials research. Part B, Applied biomaterials Quade, M., Vater, C., Schlootz, S., Bolte, J., Langanke, R., Bretschneider, H., Gelinsky, M., Goodman, S. B., Zwingenberger, S. 2019

  Abstract

  The application of strontium is one option for the clinical treatment of osteoporosis-a disease characterized by reduced bone density and quality-in order to reduce the risk of vertebral and nonvertebral fractures. Unlike other drugs used in osteoporosis therapy, strontium shows a dual effect on bone metabolism by attenuating cellular resorption and simultaneously enhancing new bone tissue formation. Current concerns regarding the systemic application of highly dosed strontium ranelate led to the development of strontium-modified scaffolds based on mineralized collagen (MCM) capable to release biologically active Sr2+ ions directly at the fracture site. In this study, we investigated the regenerative potential of these scaffolds. For in vitro investigations, human mesenchymal stromal cells were cultivated on the scaffolds for 21days (w/ and w/o osteogenic supplements). Biochemical analysis revealed a significant promoting effect on proliferation rate and osteogenic differentiation on strontium-modified scaffolds. In vivo, scaffolds were implanted in a murine segmental bone defect model-partly additionally functionalized with the osteogenic growth factor bone morphogenetic protein 2 (BMP-2). After 6 weeks, bridging calluses were obtained in BMP-2 functionalized scaffolds; the quality of the newly formed bone tissue by means of morphological scores was clearly enhanced in strontium-modified scaffolds. Histological analysis revealed increased numbers of osteoblasts and blood vessels, decreased numbers of osteoclasts, and significantly enhanced mechanical properties. These results indicate that the combined release of Sr2+ ions and BMP-2 from the biomimetic scaffolds is a promising strategy to enhance bone regeneration, especially in patients suffering from osteoporosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.

  View details for PubMedID 30950569

• Stem Cells and Platelet-Rich Plasma Injections for Advanced Hip and Knee Arthritis: Enthusiasm Outpaces Science. The Journal of arthroplasty Browne, J. A., Nho, S. J., Goodman, S. B., Callaghan, J. J., Della Valle, C. J. 2019

  View details for PubMedID 31000403

• American Association of Hip and Knee Surgeons, Hip Society, and Knee Society Position Statement on Biologics for Advanced Hip and Knee Arthritis. The Journal of arthroplasty Browne, J. A., Nho, S. J., Goodman, S. B., Della Valle, C. J. 2019

  View details for PubMedID 31005436

• Preconditioned or IL4-Secreting Mesenchymal Stem Cells Enhanced Osteogenesis at Different Stages TISSUE ENGINEERING PART A Lin, T., Kohno, Y., Huang, J., Romero-Lopez, M., Maruyama, M., Ueno, M., Pajarinen, J., Nathan, K., Yao, Z., Yang, F., Wu, J. Y., Goodman, S. B. 2019

  View details for DOI 10.1089/ten.tea.2018.0292

  View details for Web of Science ID 000462509800001

• Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation FASEB JOURNAL Lin, T., Pajarinen, J., Kohno, Y., Huang, J., Maruyama, M., Romero-Lopez, M., Nathan, K., Yao, Z., Goodman, S. B. 2019; 33 (3): 4203–11

  View details for DOI 10.1096/fj.201801845R

  View details for Web of Science ID 000459794800088

• Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery: Secondary Analysis of a Randomized Clinical Trial. JAMA network open Hah, J. M., Cramer, E., Hilmoe, H., Schmidt, P., McCue, R., Trafton, J., Clay, D., Sharifzadeh, Y., Ruchelli, G., Goodman, S., Huddleston, J., Maloney, W. J., Dirbas, F. M., Shrager, J., Costouros, J. G., Curtin, C., Mackey, S. C., Carroll, I. 2019; 2 (3): e190168

  Abstract

  Importance: Acute postoperative pain is associated with the development of persistent postsurgical pain, but it is unclear which aspect is most estimable.Objective: To identify patient clusters based on acute pain trajectories, preoperative psychosocial characteristics associated with the high-risk cluster, and the best acute pain predictor of remote outcomes.Design, Setting, and Participants: A secondary analysis of the Stanford Accelerated Recovery Trial randomized, double-blind clinical trial was conducted at a single-center, tertiary, referral teaching hospital. A total of 422 participants scheduled for thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, or shoulder arthroscopy were enrolled between May 25, 2010, and July 25, 2014. Data analysis was performed from January 1 to August 1, 2018.Interventions: Patients were randomized to receive gabapentin (1200 mg, preoperatively, and 600 mg, 3 times a day postoperatively) or active placebo (lorazepam, 0.5 mg preoperatively, inactive placebo postoperatively) for 72 hours.Main Outcomes and Measures: A modified Brief Pain Inventory prospectively captured 3 surgical site pain outcomes: average pain and worst pain intensity over the past 24 hours, and current pain intensity. Within each category, acute pain trajectories (first 10 postoperative pain scores) were compared using a k-means clustering algorithm. Fifteen descriptors of acute pain were compared as predictors of remote postoperative pain resolution, opioid cessation, and full recovery.Results: Of the 422 patients enrolled, 371 patients (≤10% missing pain scores) were included in the analysis. Of these, 146 (39.4%) were men; mean (SD) age was 56.67 (11.70) years. Two clusters were identified within each trajectory category. The high pain cluster of the average pain trajectory significantly predicted prolonged pain (hazard ratio [HR], 0.63; 95% CI, 0.50-0.80; P<.001) and delayed opioid cessation (HR, 0.52; 95% CI, 0.41-0.67; P<.001) but was not a predictor of time to recovery in Cox proportional hazards regression (HR, 0.89; 95% CI, 0.69-1.14; P=.89). Preoperative risk factors for categorization to the high average pain cluster included female sex (adjusted relative risk [ARR], 1.36; 95% CI, 1.08-1.70; P=.008), elevated preoperative pain (ARR, 1.11; 95% CI, 1.07-1.15; P<.001), a history of alcohol or drug abuse treatment (ARR,1.90; 95% CI, 1.42-2.53; P<.001), and receiving active placebo (ARR, 1.27; 95% CI, 1.03-1.56; P=.03). Worst pain reported on postoperative day 10 was the best predictor of time to pain resolution (HR, 0.83; 95% CI, 0.78-0.87; P<.001), opioid cessation (HR, 0.84; 95% CI, 0.80-0.89; P<.001), and complete surgical recovery (HR, 0.91; 95% CI, 0.86-0.96; P<.001).Conclusions and Relevance: This study has shown a possible uniform predictor of remote postoperative pain, opioid use, and recovery that can be easily assessed. Future work is needed to replicate these findings.Trial Registration: ClinicalTrials.gov Identifier: NCT01067144.

  View details for PubMedID 30821824

• Factors Associated With Acute Pain Estimation, Postoperative Pain Resolution, Opioid Cessation, and Recovery Secondary Analysis of a Randomized Clinical Trial JAMA NETWORK OPEN Hah, J. M., Cramer, E., Hilmoe, H., Schmidt, P., McCue, R., Trafton, J., Clay, D., Sharifzadeh, Y., Ruchelli, G., Goodman, S., Huddleston, J., Maloney, W. J., Dirbas, F. M., Shrager, J., Costouros, J. G., Curtin, C., Mackey, S. C., Carroll, I. 2019; 2 (3)

  View details for DOI 10.1001/jamanetworkopen.2019.0168

  View details for Web of Science ID 000465424000048

• Mesenchymal stem cell-macrophage crosstalk and bone healing BIOMATERIALS Pajarinen, J., Lin, T., Gibon, E., Kohno, Y., Maruyama, M., Nathan, K., Lu, L., Yao, Z., Goodman, S. B. 2019; 196: 80–89

  View details for DOI 10.1016/j.biomaterials.2017.12.025

  View details for Web of Science ID 000459527700007

• Osteogenic ability of rat bone marrow concentrate is at least as efficacious as mesenchymal stem cells in vitro. Journal of biomedical materials research. Part B, Applied biomaterials Kohno, Y., Lin, T., Pajarinen, J., Romero-Lopez, M., Maruyama, M., Huang, J., Nathan, K., Yao, Z., Goodman, S. B. 2019

  Abstract

  Cell therapy using bone marrow concentrate (BMC) or purified and expanded mesenchymal stem cells (MSCs) has been shown to have a promising osteogenic capacity. However, few studies have directly compared their relative osteogenic ability. The aim of this study was to compare the osteogenic ability of BMC isolated by density gradient centrifugation with bone marrow-derived MSCs in vitro using the cells of 3-month-old Sprague-Dawley rats. The isolated cells were seeded onto 24-well plates (1*105 cells/well) and cultured in control growth media, osteogenic media with dexamethasone, or media without dexamethasone (which simulated the in vivo tissue environment). Alkaline phosphatase activity at week 2, osteocalcin using quantitative real-time polymerase chain reaction at week 4, and Alizarin red staining at week 4 were evaluated. In the osteogenic media with dexamethasone, BMC showed equivalent (osteocalcin) or even greater (Alizarin red staining) osteogenic ability compared to MSCs, suggesting that cross-talk among various cells in the BMC leads to greater osteogenesis. Furthermore, in the osteogenic media without dexamethasone, BMC showed equivalent (osteocalcin) or a trend for greater (Alizarin red staining) bone formation than MSCs alone. Our results suggest that BMC has at least comparable bone regeneration potential to MSCs. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2019.

  View details for PubMedID 30779478

• Improved Range of Motion and Patient-Reported Outcome Scores With Fixed-Bearing Revision Total Knee Arthroplasty for Suboptimal Axial Implant Rotation. The Journal of arthroplasty Amanatullah, D. F., Lichstein, P. M., Lundergan, W. G., Wong, W. W., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2019

  Abstract

  BACKGROUND: Suboptimal implant rotation has consequences with respect to knee kinematics and clinical outcomes. We evaluated the functional outcomes of revision total knee arthroplasty (TKA) for poor axial implant rotation.METHODS: We retrospectively reviewed 42 TKAs undergoing aseptic revision for poor axial implant rotation. We assessed improvements in Knee Society Score (KSS) and final range of motion (ROM). Subgroup analyses were performed for preoperative instability and stiffness, as well as the number of components revised and level of implant constraint used.RESULTS: Revision for poor axial rotation in isolation improved KSS from 52 ± 22 to 84 ± 25 (P < .001), and flexion increased from 105 ± 21° to 115 ± 13° (P = .001). Revision in the setting of instability significantly improved the KSS (P < .001) but did not affect ROM (P = .172). Revision in the setting of stiffness significantly improved both KSS (P < .001) and ROM (P = .002). There was no statistically significant difference between the postoperative KSS (P = .889) and final knee flexion (P = .629) with single- or both-component revision TKA for isolated poor axial rotation or between the postoperative KSS (P = .956) and final knee flexion (P = .541) with or without the use of higher constraint during revision TKA for isolated poor axial rotation.CONCLUSION: Revision TKA for poor axial alignment improves clinical outcomes scores and functional ROM.

  View details for PubMedID 30853158

• Bone Regeneration by Controlled Release of BMP-2: A Rabbit Spinal Fusion Chamber Molecular Study. Tissue engineering. Part A Hu, T., Naidu, M., Yang, Z., Lam, W. M., Ramruttun, K. A., Ren, X. F., Ng, F., Wang, M., Liu, L., Tan, K. C., Kwok, K. T., Goodman, S. B., Goh, J., Wong, H. K. 2019

  Abstract

  Recombinant human bone morphogenetic protein (rhBMP-2) has been widely used in spine fusion surgery. However, high doses of rhBMP-2 delivered with absorbable collagen sponge (ACS) has led to inflammation-related adverse conditions. Polyelectrolyte complex (PEC) control release carrier can substantially reduce the rhBMP-2 dose and complication without compromising fusion. The molecular events underlying controlled release and their effects on spinal fusion remains unknown. In this study, a rabbit interbody spinal fusion chamber was designed to provide a controlled environment for profiling molecular events during the fusion process. Study groups included Group 1, PEC with 100g rhBMP-2; Group 2, ACS with 100g rhBMP-2; Group 3, ACS with 300g rhBMP-2; Group 4, autologous bone graft and Group 5, empty chamber. Manual palpation, CT and histological analysis showed that Group 1 and 3 achieved bone fusion, while the other groups showed no signs of fusion. Gene expression profiling showed robust induction of osteogenic markers in Groups 1 and 3, with modulated early induction of inflammatory genes in the PEC group. Delivery of 100g rhBMP-2 with ACS (Group 2) resulted in less upregulation of osteogenic genes, increased inflammatory genes expression, and upregulation of osteoclastic genes compared to Group 1. These results suggest that the manner of BMP-2 release at the interbody spinal defect site could dictate the balance of in-situ osteogenic and anti-osteogenic activities, affecting fusion outcomes. The molecular evidence supports PEC for sustained release of BMP-2 for spinal interbody fusion, and the feasibility of employing this novel interbody spinal fusion chamber for future molecular studies.

  View details for PubMedID 30727849

• Editorial Comment: 2018 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2019; 477 (2): 295–96

  View details for DOI 10.1097/CORR.0000000000000602

  View details for Web of Science ID 000472544900009

• Cytotoxicity of drugs injected into joints in orthopaedics BONE & JOINT RESEARCH Busse, P., Vater, C., Stiehler, M., Nowotny, J., Kasten, P., Bretschneider, H., Goodman, S. B., Gelinsky, M., Zwingenberger, S. 2019; 8 (2): 41–48

  View details for DOI 10.1302/2046-3758.82.BJR-2018-0099.R1

  View details for Web of Science ID 000460173700001

• Cytotoxicity of drugs injected into joints in orthopaedics. Bone & joint research Busse, P., Vater, C., Stiehler, M., Nowotny, J., Kasten, P., Bretschneider, H., Goodman, S. B., Gelinsky, M., Zwingenberger, S. 2019; 8 (2): 41-48

  Abstract

  Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro.Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed.Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions.The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability.Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41-48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1.

  View details for DOI 10.1302/2046-3758.82.BJR-2018-0099.R1

  View details for PubMedID 30915209

  View details for PubMedCentralID PMC6397327

• Suboptimal patellofemoral alignment is associated with poor clinical outcome scores after primary total knee arthroplasty ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY Narkbunnam, R., Electricwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2019; 139 (2): 249–54

  View details for DOI 10.1007/s00402-018-3073-z

  View details for Web of Science ID 000458199700013

• Editorial Comment: 2018 Hip Society Proceedings. Clinical orthopaedics and related research Goodman, S. B. 2019; 477 (2): 295–96

  View details for PubMedID 30794218

• Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis NATURE COMMUNICATIONS Ji, Q., Xu, X., Kang, L., Xu, Y., Xiao, J., Goodman, S. B., Zhu, X., Li, W., Liu, J., Gao, X., Yan, Z., Zheng, Y., Wang, Z., Maloney, W. J., Ye, Q., Wang, Y. 2019; 10

  View details for DOI 10.1038/s41467-018-08277-5

  View details for Web of Science ID 000456010800010

• Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis. Nature communications Ji, Q., Xu, X., Kang, L., Xu, Y., Xiao, J., Goodman, S. B., Zhu, X., Li, W., Liu, J., Gao, X., Yan, Z., Zheng, Y., Wang, Z., Maloney, W. J., Ye, Q., Wang, Y. 2019; 10 (1): 313

  Abstract

  Osteoarthritis (OA) has been recognized as the most common chronic age-related disease. Cartilage degeneration influences OA therapy. Here we report that hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is essential for OA development. Elevated HPIP levels are found in OA patients. Col2a1-CreERT2/HPIPf/f mice exhibit obvious skeletal abnormalities compared with their HPIPf/f littermates. HPIP deficiency in mice protects against developing OA. Moreover, intra-articular injection of adeno-associated virus carrying HPIP-specific short hairpin RNA in vivo attenuates OA histological signs. Notably, in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles identify that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes. Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Furthermore, HPIP potentiates the transcriptional activity of LEF1 and acetylates histone H3 lysine 56 in the promoters of Wnt targets, suggesting that HPIP is an attractive target in OA regulatory network.

  View details for PubMedID 30659184

• Preconditioned or IL4-Secreting Mesenchymal Stem Cells Enhanced Osteogenesis at Different Stages. Tissue engineering. Part A Lin, T., Kohno, Y., Huang, J., Romero-Lopez, M., Maruyama, M., Ueno, M., Pajarinen, J., Nathan, K., Yao, Z., Yang, F., Wu, J., Goodman, S. B. 2019

  Abstract

  Chronic inflammation-associated bone diseases involve continuous destruction and impaired regeneration of bone. Mesenchymal stem cell (MSC)-based therapy has great potential to modulate inflammatory responses and enhance tissue regeneration. We previously showed that lipopolysaccharide [LPS] plus TNF preconditioned MSCs or genetically modified inflammation-sensing (driven by NFB activation) IL4-secreting MSCs enhanced immunomodulation of macrophages to the more desired tissue repaired M2 type. In the current study, the paracrine regulation of therapeutic MSCs on the pro-inflammatory response and osteogenesis of macrophage-MSC co-cultures (representing endogenous cells) was examined using an in vitro transwell system. In the co-cultures, IL4-secreting MSCs decreased TNF and iNOS expression, and increased Arginase 1 and CD206 expression in the presence of LPS-contaminated polyethylene particles. The preconditioned MSCs decreased TNF and CD206 expression in the bottom MSC-macrophage co-cultures in the presence of contaminated particles. In osteogenesis assays, IL4-secreting MSCs decreased ALP expression, but increased alizarin red staining in the presence of contaminated particles. The preconditioned MSCs increased ALP and osteocalcin expression, and had no significant effect on alizarin red staining. These results suggest that potential treatments using preconditioned MSCs at an earlier stage, or IL4-secreting MSCs at a later stage could enhance bone regeneration in inflammatory conditions including periprosthetic osteolysis.

  View details for PubMedID 30652628

• 2-step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Bolte, J., Vater, C., Culla, A. C., Ahlfeld, T., Nowotny, J., Kasten, P., Disch, A. C., Goodman, S. B., Gelinsky, M., Stiehler, M., Zwingenberger, S. 2019

  Abstract

  Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre-differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre-differentiation of mesenchymal stromal cells (MSCs) and PL on bone regeneration and vascularization. Bone marrow from 4 different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy-two mice were randomized to 6 groups (Control, PL, BMC, BMC+PL, pre-differentiated MSCs, pre-differentiated MSCs+PL). The influence of PL, BMC and pre-differentiated MSCs was investigated systematically in a 2mm femoral bone defect model. After a 6-week follow-up, the pre-differentiated MSCs+PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre-differentiated MSCs for treatment of a critical-size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30628121

• Angiotensin receptor blockade mimics the effect of exercise on recovery after orthopaedic trauma by decreasing pain and improving muscle regeneration. The Journal of physiology Tawfik, V. L., Quarta, M. n., Paine, P. n., Forman, T. E., Pajarinen, J. n., Takemura, Y. n., Goodman, S. B., Rando, T. A., Clark, J. D. 2019

  Abstract

  Our tibial fracture orthopaedic injury model in mice recapitulates the major manifestations of complex trauma including nociceptive sensitization, bone fracture, muscle fibrosis and muscle fibre loss. Delayed exercise after complex orthopaedic trauma results in decreased muscle fibrosis and improved pain Losartan, an angiotensin-receptor blocker with antifibrotic abilities, recapitulates the effect of exercise on post-injury recovery and may provide an enhanced recovery option for those who are unable to exercise after injury ABSTRACT: Chronic pain and disability after limb injury are major public health problems. Early mobilization after injury improves functional outcomes for patients but when and how to implement rehabilitation strategies remains a clinical challenge. Additionally, whether the beneficial effects of exercise can be reproduced using pharmacological tools remains unknown and may benefit patients who are unable to exercise due to immobilization. We developed a murine model of orthopaedic trauma combining tibia fracture and pin fixation with muscle damage. Behavioral measures included mechanical nociceptive thresholds and distances run on exercise wheels. Bone healing was quantified using microCT scanning, and muscle fibre size distribution and fibrosis were followed using immunohistochemistry. We found that the model provided robust mechanical allodynia, fibrosis and a shift to smaller average muscle fibre size lasting up to 5 weeks from injury. We also observed that allowing "late" (weeks 1-2) rather than "early" (weeks 0-1) exercise after injury resulted in greater overall running activity and greater reversal of allodynia. In parallel, the late running paradigm was associated with reduced muscle fibrosis, earlier increase in muscle fibre diameter and a short-term benefit in reducing callus volume. Providing the anti-fibrotic angiotensin receptor blocker losartan to mice in drinking water reduced both allodynia and muscle fibrosis. Combining losartan and late exercise provided no additional benefit. We conclude that early healing after orthopaedic trauma must be allowed prior to the initiation of exercise to achieve optimal pain, functional and physiological outcomes and that losartan is a viable candidate for translational studies. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1113/JP278991

  View details for PubMedID 31784993

• Biomaterials in Orthopaedics ENCYCLOPEDIA OF BIOMEDICAL ENGINEERING, VOL 1 Gibon, E., Goodman, S. B., Narayan, R. 2019: 301–7

  View details for DOI 10.1016/B978-0-12-801238-3.11032-3

  View details for Web of Science ID 000517437200026

• Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment. Journal of clinical medicine Goodman, S. B., Gallo, J. n. 2019; 8 (12)

  Abstract

  Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone-implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.

  View details for DOI 10.3390/jcm8122091

  View details for PubMedID 31805704

• Diagnosis and Management of Implant Debris-Associated Inflammation. Expert review of medical devices Goodman, S. B., Gallo, J. n., Gibon, E. F., Takagi, M. n. 2019

  Abstract

  Introduction: Total joint replacement is one of the most common, safe and efficacious operations in all of surgery. However, one major long-standing and unresolved issue is the adverse biological reaction to byproducts of wear from the bearing surfaces and modular articulations. These inflammatory reactions are mediated by the innate and adaptive immune systems.Areas Covered: We review the etiology and pathophysiology of implant debris-associated inflammation, the clinical presentation and detailed work-up of these cases, and the principles and outcomes of non-operative and operative management. Furthermore, we suggest future strategies for prevention and novel treatments of implant related adverse biological reactions.Expert Commentary: The generation of byproducts from joint replacements is inevitable, due to repetitive loading of the implants. A clear understanding of the relevant biological principles, clinical presentations, investigative measures and treatments for implant-associated inflammatory reactions and periprosthetic osteolysis will help identify and treat patients with this issue earlier and more effectively. Although progressive implant-associated osteolysis is currently a condition that is treated surgically, with further research, it is hoped that non-operative biological interventions could prolong the lifetime of joint replacements that are otherwise functional and still salvageable.

  View details for DOI 10.1080/17434440.2020.1702024

  View details for PubMedID 31810395

• The Cost of Malnutrition in Total Joint Arthroplasty. The Journal of arthroplasty Bala, A. n., Ivanov, D. V., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2019

  Abstract

  Malnutrition is a known risk factor for complications and adverse outcomes after elective total joint arthroplasty (TJA), but little is known about the burden this risk factor places on the healthcare system. The purpose of this study was to evaluate the 90-day impact of malnutrition on medical and surgical complications and understand the increase in global reimbursements associated with TJA in malnourished patients.We queried a combined private-payer and Medicare database from 2007 to 2016 for TJA using International Classification of Diseases, 9th revision and Current Procedural Terminology codes. Patients with serum albumin level of <3.5 g/dL were gender, age, and mean Elixhauser Comorbidity Index matched against a cohort with a normal serum albumin level. Odds ratios and confidence intervals were calculated for complications at 90 days postoperatively. Mean index and 90-day global reimbursements were calculated for the two matched groups and compared using P-values.3053 protein malnourished patients receiving TJA were identified, and 12,202 matched protein nourished patients receiving TJA served as controls. At 90 days, the malnourished groups had increased risk for failure of multiple organ systems, periprosthetic joint infection, and reoperation. The mean 90-day increase in reimbursement was $3875 associated with performing a TJA on a protein malnourished patient (P < .001).This study demonstrates an association between malnourished patients and postoperative complications as well as significantly increased reimbursements. Understanding the reimbursement increases at 90 days for TJA in protein malnourished patients is important in the era of bundled payments.

  View details for DOI 10.1016/j.arth.2019.11.018

  View details for PubMedID 31879158

• Does Bariatric Surgery Normalize Risks After Total Knee Arthroplasty? Administrative Medicare Data. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews Meller, M. M., Goodman, S. n., Gonzalez, M. H., Lau, E. n. 2019; 3 (12)

  Abstract

  Patients with morbid obesity, defined as body mass index of greater than 40 kg/m2, are being referred for weight loss and bariatric surgery before being accepted for a total knee arthroplasty (TKA). Previous studies have identified the risks associated with doing a TKA in an individual with an increased body mass index. We now present data identifying the same risks in individuals who have undergone bariatric surgery before submitting to TKA.(1) Has the bariatric surgery improved the risk profile for the subsequent TKA? (2) Does the type of bariatric procedure matter?A retrospective cohort study was conducted of patients who underwent bariatric surgery followed by TKA using Medicare hospital claims data. A study was undertaken using the Current Procedure Terminology codes and International Classification of Diseases-9 and International Classification of Diseases-10 for bariatric surgery. These identified entries were then cross-referenced to individuals who later underwent TKA, identified by CPT 27447, between 2004 and 2016. Twelve different types of complications which occurred in the 90-day period after the TKA were analyzed.Postbariatric bypass surgery patients showed a markedly elevated risk in most complications examined. In each category, the type of previous gastric surgery had notable differences in the post-TKA complication profile. In the implant failure category, the data demonstrated an even greater risk after a gastric bypass. When postbariatric patients were compared with morbidly obese individuals who had not undergone bariatric surgery, the hazard ratios (HRs) were markedly elevated for death (HR 1.47/bypass), implant failure (HR 1.58/sleeve), and pneumonia (HR 1.68/bypass).(1) Submitting to bariatric surgery is not sufficient to normalize risks. (2) The type of previous bariatric procedure is associated with the type of complications encountered. (3) We were unable to attribute TKA to bariatric failures. (4) Health systems and health care providers should be cautious in withholding care for patients with morbid obesity.

  View details for DOI 10.5435/JAAOSGlobal-D-19-00102

  View details for PubMedID 32072123

  View details for PubMedCentralID PMC7004493

• Optimization and characterization of calcium phosphate transfection in mesenchymal stem cells. Tissue engineering. Part C, Methods Lo, C. W., Lin, T. H., Ueno, M. n., Romero-Lopez, M. n., Maruyama, M. n., Kohno, Y. n., Rhee, C. n., Yao, Z. n., Pérez-Cruz, M. n., Meyer, E. n., Goodman, S. B. 2019

  Abstract

  Mesenchymal stem cells (MSCs) have been used as a therapy to modulate diverse biological processes. To fulfill the requirements for different MSC therapies, safe and effective gene transfer methods for MSCs are critical. Calcium phosphate transfection is an inexpensive and well-described method without discernible biosafety issues; however, an optimal protocol has not been developed for MSCs. In this report, we optimized the protocol of calcium phosphate transfection for murine MSCs, and compared this protocol with other gene transfer methods in different strains of mice and in human cells. We found that transfection efficiency and cell viability showed an inverse relationship depending on serum concentration during the process of calcium phosphate transfection, in which 2% serum was chosen in the optimized protocol. The optimized protocol of calcium phosphate transfection showed a fine balance between efficiency (about 70-80%) and viability (doubling original cell number) compared to other methods. Human MSCs were more resistant to this protocol (about 30% efficiency) compared with murine MSCs. Moreover, MSC potential for osteogenesis, adipogenesis, and chondrogenesis was not affected by calcium phosphate transfection. Finally, MSCs transfected with the luciferase gene were injected into the murine distal femoral bone marrow cavity to monitor gene expression overtime in vivo. MSCs in the bone marrow environment showed extended expression of the luciferase that was transfected by calcium phosphate. This report provides an optimized protocol for calcium phosphate transfection for murine MSCs and characterizes gene over-expression in MSCs in the in vitro and in vivo environments.

  View details for DOI 10.1089/ten.TEC.2019.0147

  View details for PubMedID 31441373

• Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone & joint research Nathan, K. n., Lu, L. Y., Lin, T. n., Pajarinen, J. n., Jämsen, E. n., Huang, J. F., Romero-Lopez, M. n., Maruyama, M. n., Kohno, Y. n., Yao, Z. n., Goodman, S. B. 2019; 8 (10): 481–88

  Abstract

  Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage-mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures.A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion.We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis.These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific.Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481-488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2.

  View details for DOI 10.1302/2046-3758.810.BJR-2018-0231.R2

  View details for PubMedID 31728188

  View details for PubMedCentralID PMC6825050

• Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis JOURNAL OF ARTHROPLASTY Yoon, B., Jones, L. C., Chen, C., Cheng, E. Y., Cui, Q., Drescher, W., Fukushima, W., Gangji, V., Goodman, S. B., Ha, Y., Hernigou, P., Hungerford, M., Iorio, R., Jo, W., Khanduja, V., Kim, H., Kim, S., Kim, T., Lee, H., Lee, M. S., Lee, Y., Lee, Y., Mont, M. A., Sakai, T., Sugano, N., Takao, M., Yamamoto, T., Koo, K. 2019; 34 (1): 163-+

  View details for DOI 10.1016/j.arth.2018.09.005

  View details for Web of Science ID 000452539200028

• Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis JOURNAL OF ARTHROPLASTY Yoon, B., Jones, L. C., Chen, C., Cheng, E. Y., Cui, Q., Drescher, W., Fukushima, W., Gangji, V., Goodman, S. B., Ha, Y., Hernigou, P., Hungerford, M., Iorio, R., Jo, W., Khanduja, V., Kim, H., Kim, S., Kim, T., Lee, H., Lee, M. S., Lee, Y., Lee, Y., Mont, M. A., Sakai, T., Sugano, N., Takao, M., Yamamoto, T., Koo, K. 2019; 34 (1): 169-+

  View details for DOI 10.1016/j.arth.2018.09.006

  View details for Web of Science ID 000452539200029

• Hip or spine surgery first? The bone & joint journal Liu, N. n., Goodman, S. B., Lachiewicz, P. F., Wood, K. B. 2019; 101-B (6_Supple_B): 37–44

  Abstract

  Patients may present with concurrent symptomatic osteoarthritis (OA) of the hip and degenerative disorders of the lumbar spine, with surgical treatment being indicated for both. Whether arthroplasty of the hip or spinal surgery should be performed first remains uncertain.Clinical scenarios were devised for a survey asking the preferred order of surgery and the rationale for this decision for five fictional patients with both OA of the hip and degenerative lumbar disorders. These were symptomatic OA of the hip and: 1) lumbar spinal stenosis with neurological claudication; 2) lumbar degenerative spondylolisthesis with leg pain; 3) lumbar disc herniation with leg weakness; 4) lumbar scoliosis with back pain; and 5) thoracolumbar disc herniation with myelopathy. This survey was sent to 110 members of The Hip Society and 101 members of the Scoliosis Research Society. The choices of the surgeons were compared among scenarios and between surgical specialties using the chi-squared test. The free-text comments were analyzed using text-mining.Responses were received from 51 hip surgeons (46%) and 37 spine surgeons (37%). The percentages of hip surgeons recommending 'hip first' differed significantly among scenarios: 59% for scenario 1; 73% for scenario 2; 47% for scenario 3; 47% for scenario 4; and 10% for scenario 5 (p < 0.001). The percentages of spine surgeons recommending 'hip first' were 49% for scenario 1; 70% for scenario 2; 19% for scenario 3; 78% for scenario 4; and 0% for scenario 5. There were significant differences between the groups for scenarios 3 (more hip surgeons recommended 'hip first'; p = 0.012) and 4 (more hip surgeons recommended 'spine first'; p = 0.006).In patients with coexistent OA of the hip and degenerative disorders of the spine, the question of 'hip or spinal surgery first' elicits relatively consistent answers in some clinical scenarios, but remains controversial in others, even for experienced surgeons. The nature of neurological symptoms can influence surgeons' decision-making. Cite this article: Bone Joint J 2019;101-B(6 Supple B):37-44.

  View details for DOI 10.1302/0301-620X.101B6.BJJ-2018-1073.R1

  View details for PubMedID 31146559

• CORR Insights®: CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor- γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation. Clinical orthopaedics and related research Goodman, S. B. 2019

  View details for DOI 10.1097/CORR.0000000000000789

  View details for PubMedID 31107340

• IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis. eLife Wang, Q. n., Lepus, C. M., Raghu, H. n., Reber, L. L., Tsai, M. M., Wong, H. H., von Kaeppler, E. n., Lingampalli, N. n., Bloom, M. S., Hu, N. n., Elliott, E. E., Oliviero, F. n., Punzi, L. n., Giori, N. J., Goodman, S. B., Chu, C. R., Sokolove, J. n., Fukuoka, Y. n., Schwartz, L. B., Galli, S. J., Robinson, W. H. 2019; 8

  Abstract

  Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and murine osteoarthritic joint tissues. Using genetic models of mast cell deficiency, we demonstrate that lack of mast cells attenuates osteoarthritis in mice. Using genetic and pharmacologic approaches, we show that the IgE/FcεRI/Syk signaling axis is critical for the development of osteoarthritis. We find that mast cell-derived tryptase induces inflammation, chondrocyte apoptosis, and cartilage breakdown. Our findings demonstrate a central role for IgE-dependent mast cell activation in the pathogenesis of osteoarthritis, suggesting that targeting mast cells could provide therapeutic benefit in human osteoarthritis.This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

  View details for PubMedID 31084709

• Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof-of-Concept Study in Patients CLINICAL CANCER RESEARCH Theruvath, A. J., Nejadnik, H., Muehe, A. M., Gassert, F., Lacayo, N. J., Goodman, S. B., Daldrup-Link, H. E. 2018; 24 (24): 6223–29

  View details for DOI 10.1158/1078-0432.CCR-18-1687

  View details for Web of Science ID 000453267600016

• Statin use is associated with less postoperative cardiac arrhythmia after total hip arthroplasty. Hip international : the journal of clinical and experimental research on hip pathology and therapy Chen, M. J., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Aaronson, A. J., Amanatullah, D. F. 2018: 1120700018816091

  Abstract

  INTRODUCTION:: While statins have been found to reduce postoperative atrial fibrillation after cardiac surgery, little is known about their use in total hip arthroplasty (THA). This study investigated if statins would similarly reduce postoperative arrhythmias in patients undergoing THA.METHODS:: We queried a large Medicare and private-payer database from 2005 to 2012 and identified 12,075 patients who were on a statin prior to THA. We then age and sex matched 34,446 non-statin users who underwent THA. Baseline comorbidities and postoperative complications were obtained and assessed via standard descriptive statistics.RESULTS:: The statin users had more preoperative comorbidities including congestive heart failure, valvular heart disease, pulmonary and renal disease, diabetes, hypertension, obesity, and anaemia (all p values < 0.001). Postoperatively, the statin users had a statistically higher 90-day incidence of transfusion, acute renal failure, heart failure, pneumonia, and sepsis/shock. All new-onset cardiac arrhythmia was significantly less frequent in the statin group at 2weeks (3.88% vs. 4.72%, p < 0.001), 30days (4.47% vs. 5.29%, p < 0.001), and 90days (5.44% vs. 6.31%, p = 0.001) postoperative. There was no difference in the frequency of venous thromboembolism, myocardial infarction, postoperative anaemia, or bleeding at 90days postoperative.DISCUSSION:: Despite being medically sicker at baseline with multiple risk factors for atrial fibrillation compared to the non-statin users, the statin users displayed a consistently lower occurrence of postoperative cardiac arrhythmia in this retrospective cohort study. Statins may therefore be beneficial in the preoperative optimisation of medically complex patients undergoing THA.

  View details for PubMedID 30526117

• Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Lin, T., Pajarinen, J., Kohno, Y., Huang, J., Maruyama, M., Romero-Lopez, M., Nathan, K., Yao, Z., Goodman, S. B. 2018: fj201801845R

  Abstract

  Mesenchymal stem cell (MSC)-mediated immunomodulation affects both innate and adaptive immune systems. These responses to environmental cues, such as pathogen-associated molecular patterns, damage-associated molecular patterns, or proinflammatory cytokines, are crucial for resolution of inflammation, as well as successful tissue healing and regeneration. We observed that intermittent, repeated exposure of MSCs to LPS induced stronger NF-kappaB activation than singular stimulation. A similar phenomenon, named innate immune memory or trained immunity, has been reported with macrophages. However, the potential regulation of "immune memory" in nonclassic immune cells, such as MSCs, has not been reported. In the current study, we chose IFN-gamma plus TNF-alpha restimulation-induced iNOS expression as a model of MSC activation, because IFN-gamma and TNF-alpha play crucial roles in MSC-mediated immunomodulation. The iNOS expression was enhanced in LPS-trained MSCs, 3 d after a washout period following primary stimulation. LPS-trained MSCs enhanced the anti-inflammatory (arginase 1 and CD206) marker expression, but decreased the proinflammatory marker (TNF-alpha, IL-1beta, iNOS, and IL-6) expression using an MSC-macrophage coculture model. In contrast, LPS-trained MSCs demonstrated a defective regulation on CD4 T-cell proliferation. Mechanistic studies suggested that histone methylation and the JNK pathway are involved in LPS-trained immunomodulation in MSCs. Our results demonstrate differential immunomodulatory effects of trained MSCs on macrophages and T cells. These immunomodulatory consequences are critical, because they will have a major impact on current MSC-based cell therapies.-Lin, T., Pajarinen, J., Kohno, Y., Huang, J.-F., Maruyama, M., Romero-Lopez, M., Nathan, K., Yao, Z., Goodman, S. B. Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation.

  View details for PubMedID 30521384

• The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis BIOMATERIALS Maruyama, M., Nabeshima, A., Pan, C., Behn, A. W., Thio, T., Lin, T., Pajarinen, J., Kawai, T., Takagi, M., Goodman, S. B., Yang, Y. 2018; 187: 39–46

  View details for DOI 10.1016/j.biomaterials.2018.09.030

  View details for Web of Science ID 000449446000005

• Erratum to: Can a Conical Implant Successfully Address Complex Anatomy in Primary THA? Radiographs and Hip Scores at Early Followup. Clinical orthopaedics and related research Zhang, G., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2018; 476 (12): 2458

  View details for PubMedID 30427315

• Proximal Femoral Shape Changes the Risk of a Leg Length Discrepancy After Primary Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Lim, Y., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018; 33 (12): 3699–3703

  View details for DOI 10.1016/j.arth.2018.08.008

  View details for Web of Science ID 000450300700019

• Can a Conical Implant Successfully Address Complex Anatomy in Primary THA? Radiographs and Hip Scores at Early Followup (vol 474, pg 459, 2016) CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Zhang, G., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2018; 476 (12): 2458

  View details for DOI 10.1097/CORR.0000000000000540

  View details for Web of Science ID 000457619900027

• Suboptimal patellofemoral alignment is associated with poor clinical outcome scores after primary total knee arthroplasty. Archives of orthopaedic and trauma surgery Narkbunnam, R., Electricwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2018

  Abstract

  BACKGROUND: Proper patellofemoral alignment is an important goal in total knee arthroplasty (TKA). Acceptable patellar alignment is defined as patellar tilt less than or equal to 5° and patellar displacement less than or equal to 5mm. Previous studies reported an incidence of post-operative patellar malalignment in TKA from 7 to 35%. However, correlation between patellar malalignment and clinical outcome after TKA remains unclear. The purpose of the present study was to evaluate the effect of patellar tilt and displacement on the clinical outcome of TKA.METHODS: A retrospective review of 138 primary TKAs with a minimum of 2 year follow-up is reported. Pre-operative and post-operative mechanical axis, patellar tilting angle and patellar displacement were measured. Clinical outcomes were evaluated by the knee functional scores including the Knee Society Score (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario McMaster University Osteoarthritis Index (WOMAC) at final follow-up.RESULTS: Forty-two (30%) primary TKAs had suboptimal patellofemoral alignment with a patellar tilt angle greater than 5° or lateral patellar displacement of more than 5mm. There was no statistical difference in pre-operative mechanical axis, pre-operative patellar tilt angle, or pre-operative lateral patellar displacement between the primary TKAs with proper patellofemoral alignment and those with suboptimal alignment. Patients with post-operative patellar tilt or displacement had clinically significant reductions in KSS, KOOS, and WOMAC when compared with patients without post-operative patellar tilt or displacement. The odds of having a fair or poor post-operative result, an odds ratio of 3.4 (95% CI 1.6-7.2) for KSS, 6.4 (95% CI 2.9-14.2) for KOOS, and 5.9 (95% CI 2.6-13.5) for WOMAC, were associated with suboptimal patellofemoral alignment.CONCLUSION: Establishing proper patellofemoral alignment remains an essential goal of primary TKA. There is a strong association between suboptimal post-operative patellofemoral alignment and poor clinical outcome scores after primary TKA.

  View details for PubMedID 30483917

• Strategies for Weight Reduction Prior to Total Joint Arthroplasty JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Chen, M. J., Bhowmick, S., Beseler, L., Schneider, K. L., Kahan, S. I., Morton, J. M., Goodman, S. B., Amanatullah, D. F. 2018; 100 (21)

  View details for DOI 10.2106/JBJS.18.00020

  View details for Web of Science ID 000449435200015

• Strategies for Weight Reduction Prior to Total Joint Arthroplasty. The Journal of bone and joint surgery. American volume Chen, M. J., Bhowmick, S., Beseler, L., Schneider, K. L., Kahan, S. I., Morton, J. M., Goodman, S. B., Amanatullah, D. F. 2018; 100 (21): 1888–96

  View details for PubMedID 30399084

• Effect of Computer Navigation on Complication Rates Following Unicompartmental Knee Arthroplasty JOURNAL OF ARTHROPLASTY Chona, D., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. E. 2018; 33 (11): 3437-+

  View details for DOI 10.1016/j.arth.2018.06.030

  View details for Web of Science ID 000446993500014

• NF kappa B sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Lin, T., Kohno, Y., Huang, J., Romero-Lopez, M., Pajarinen, J., Maruyama, M., Nathan, K., Yao, Z., Goodman, S. B. 2018; 106 (10): 2744–52

  View details for DOI 10.1002/jbm.a.36504

  View details for Web of Science ID 000448177600018

• Surgery Before Subspecialty Referral for Periprosthetic Knee Infection Reduces the Likelihood of Infection Control CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Song, S., Goodman, S. B., Suh, G., Finlay, A. K., Huddleston, J. I., Maloney, W. J., Amanatullah, D. F. 2018; 476 (10): 1995–2002

  View details for DOI 10.1097/CORR.0000000000000423

  View details for Web of Science ID 000452515700021

• Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis. The Journal of arthroplasty Yoon, B., Jones, L. C., Chen, C., Cheng, E. Y., Cui, Q., Drescher, W., Fukushima, W., Gangji, V., Goodman, S. B., Ha, Y., Hernigou, P., Hungerford, M., Iorio, R., Jo, W., Khanduja, V., Kim, H., Kim, S., Kim, T., Lee, H. Y., Lee, M. S., Lee, Y., Lee, Y. J., Mont, M. A., Sakai, T., Sugano, N., Takao, M., Yamamoto, T., Koo, K. 2018

  Abstract

  BACKGROUND: Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH.METHODS: In June of 2017, Association Research Circulation Osseous formed a task force to conduct a Delphi survey. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey included questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, consensus was reached on the classification criteria. The response rates for the 3 Delphi rounds were 100% (round 1), 96% (round 2), and 100% (round 3).RESULTS: The consensus on the classification criteria of alcohol-associated ONFH included the following: (1) patients should have a history of alcohol intake >400 mL/wk (320 g/wk, any type of alcoholic beverage) of pure ethanol for more than 6 months; (2) ONFH should be diagnosed within 1 year after alcohol intake of this dose; and (3) patients should not have other risk factor(s).CONCLUSION: ARCO-established classification criteria to standardize clinical studies concerning AA-ONFH.

  View details for PubMedID 30348559

• Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis. The Journal of arthroplasty Yoon, B., Jones, L. C., Chen, C., Cheng, E. Y., Cui, Q., Drescher, W., Fukushima, W., Gangji, V., Goodman, S. B., Ha, Y., Hernigou, P., Hungerford, M., Iorio, R., Jo, W., Khanduja, V., Kim, H., Kim, S., Kim, T., Lee, H. Y., Lee, M. S., Lee, Y., Lee, Y. J., Mont, M. A., Sakai, T., Sugano, N., Takao, M., Yamamoto, T., Koo, K. 2018

  Abstract

  BACKGROUND: Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme.METHODS: In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively.RESULTS: The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids.CONCLUSION: Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.

  View details for PubMedID 30348552

• Identification of the Human Skeletal Stem Cell. Cell Chan, C. K., Gulati, G. S., Sinha, R., Tompkins, J. V., Lopez, M., Carter, A. C., Ransom, R. C., Reinisch, A., Wearda, T., Murphy, M., Brewer, R. E., Koepke, L. S., Marecic, O., Manjunath, A., Seo, E. Y., Leavitt, T., Lu, W., Nguyen, A., Conley, S. D., Salhotra, A., Ambrosi, T. H., Borrelli, M. R., Siebel, T., Chan, K., Schallmoser, K., Seita, J., Sahoo, D., Goodnough, H., Bishop, J., Gardner, M., Majeti, R., Wan, D. C., Goodman, S., Weissman, I. L., Chang, H. Y., Longaker, M. T. 2018; 175 (1): 43

  Abstract

  Stem cell regulation and hierarchical organization ofhuman skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

  View details for PubMedID 30241615

• The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis. Biomaterials Maruyama, M., Nabeshima, A., Pan, C., Behn, A. W., Thio, T., Lin, T., Pajarinen, J., Kawai, T., Takagi, M., Goodman, S. B., Yang, Y. P. 2018; 187: 39–46

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a debilitating disease that may progress to femoral head collapse and subsequently, degenerative arthritis. Although injection of bone marrow-derived mononuclear cells (BMMCs) is often performed with core decompression (CD) in the early stage of ONFH, these treatments are not always effective in prevention of disease progression and femoral head collapse. We previously described a novel 3D printed, customized functionally-graded scaffold (FGS) that improved bone growth in the femoral head after CD in a normal healthy rabbit, by providing structural and mechanical guidance. The present study demonstrates similar results of the FGS in a rabbit steroid-induced osteonecrosis model. Furthermore, the injection of BMMCs into the CD decreased the osteonecrotic area in the femoral head. Thus, the combination of FGS and BMMC provides a new therapy modality that may improve the outcome of CD for early stage of ONFH by providing both enhanced biological and biomechanical cues to promote bone regeneration in the osteonecrotic area.

  View details for PubMedID 30292940

• Identification of the Human Skeletal Stem Cell CELL Chan, C. F., Gulati, G. S., Sinha, R., Tompkins, J., Lopez, M., Carter, A. C., Ransom, R. C., Reinisch, A., Wearda, T., Murphy, M., Brewer, R. E., Koepke, L. S., Marecic, O., Manjunath, A., Seo, E., Leavitt, T., Lu, W., Allison Nguyen, Conley, S. D., Salhotra, A., Ambrosi, T. H., Borrelli, M. R., Siebel, T., Chan, K., Schallmoser, K., Seita, J., Sahoo, D., Goodnough, H., Bishop, J., Gardner, M., Majeti, R., Wan, D. C., Goodman, S., Weissman, I. L., Chang, H. Y., Longaker, M. T. 2018; 175 (1): 43-+

  View details for DOI 10.1016/j.cell.2018.07.029

  View details for Web of Science ID 000445120000013

• Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof of Concept Study in Patients. Clinical cancer research : an official journal of the American Association for Cancer Research Theruvath, A. J., Nejadnik, H., Muehe, A. M., Gassert, F., Lacayo, N. J., Goodman, S. B., Daldrup-Link, H. E. 2018

  Abstract

  PURPOSE: Osteonecrosis (ON) is a devastating complication of high dose corticosteroid therapy in cancer patients. Core decompression for prevention of bone collapse has been recently combined with the delivery of autologous concentrated bone marrow aspirates. The purpose of our study was to develop an imaging test for the detection of transplanted bone marrow cells in ON lesions.EXPERIMENTAL DESIGN: In a prospective proof-of-concept clinical trial (NCT02893293), we performed serial MR imaging studies of nine hip joints of seven ON patients before and after core decompression. 24-48hours prior to the surgery, we injected ferumoxytol nanoparticles intravenously to label cells in normal bone marrow with iron oxides. During the surgery, iron labeled bone marrow cells were aspirated from the iliac crest, concentrated and then injected into the decompression track. Following surgery, patients received follow-up MRI up to 6 months after bone marrow cell transplantation.RESULTS: Iron labeled cells could be detected in the access canal by a dark (negative) signal on T2*-weighted MR images. T2* relaxation times of iron labeled cell transplants were significantly lower compared to unlabeled cell transplants of control patients who were not injected with ferumoxytol (P = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different (P = 1), suggesting that the added ferumoxytol administration did not negatively affect bone repair.CONCLUSIONS: This immediately clinically applicable imaging test could become a powerful new tool to monitor the effect of therapeutic cells on bone repair outcomes after corticosteroid-induced osteonecrosis.

  View details for PubMedID 30224340

• Periprosthetic Bacterial Biofilm and Quorum Sensing JOURNAL OF ORTHOPAEDIC RESEARCH Mooney, J. A., Pridgen, E. M., Manasherob, R., Suh, G., Blackwell, H. E., Barron, A. E., Bollyky, P. L., Goodman, S. B., Amanatullah, D. F. 2018; 36 (9): 2331–39

  View details for DOI 10.1002/jor.24019

  View details for Web of Science ID 000443808900002

• A Tissue Engineering Approach for Treating Early Osteonecrosis of the Femoral Head REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE Goodman, S. B. 2018; 4 (3): 162–66

  View details for DOI 10.1007/s40883-018-0058-y

  View details for Web of Science ID 000445496200006

• Surgery Before Subspecialty Referral for Periprosthetic Knee Infection Reduces the Likelihood of Infection Control. Clinical orthopaedics and related research Song, S. Y., Goodman, S. B., Suh, G., Finlay, A. K., Huddleston, J. I., Maloney, W. J., Amanatullah, D. F. 2018

  Abstract

  BACKGROUND: Failure to control a periprosthetic joint infection (PJI) often leads to referral of the patient to a tertiary care institution. However, there are no data regarding the effect of prior surgical intervention for PJI on subsequent infection control.QUESTIONS/PURPOSES: (1) Is the likelihood of 2-year infection-free survival worse if an initial surgery for PJI was performed before referral to a tertiary care center when compared with after referral for definitive treatment? (2) Is the likelihood of identifying a causal organism during PJI worse if the initial surgery for PJI was performed before referral to a tertiary care center when compared with after referral for definitive treatment? (3) We calculated how many patients are harmed by the practice of surgically attempting to treat PJI before referral to a tertiary care center when compared with treatment after referral to a tertiary care center for definitive treatment.METHODS: Among 179 patients (182 TKAs) who were referred for PJI between 2004 and 2014, we retrospectively studied 160 patients (163 TKAs) who had a minimum of 2 years of followup after surgical treatment or had failure of treatment within 2 years. Nineteen TKAs (19 patients) were excluded from the study; 13 patients (7%) had < 2-year followup, three patients had infected periprosthetic fractures, and three patients had infected extensor mechanism reconstruction. Eighty-six patients (88 TKAs, two bilateral [54%]) had no surgical treatment before referral to our institution for PJI management, and 75 patients (75 TKAs [46%]) had PJI surgery before referral. The mean followup was 2.4 ± 1.2 years for patients with PJI surgery before referral and 2.8 ± 1.3 years for patients with no surgery before referral (p = 0.065). Infection-free survival was defined as prosthesis retention without further surgical intervention or antibiotic suppression. During the period, further surgical intervention generally was performed after failure of irrigation and debridement, a one- or two-stage procedure, or between stages of a two-stage reimplantation without documentation of an eradiated infection, and antibiotic suppression generally was used when patients were not medically sound for surgical intervention or definitive implants were placed after the second of a two-stage procedure with positive cultures; these criteria were applied similarly to all patients during this time period in both study groups. Endpoints were assessed using a longitudinally maintained institutional database, and the treating surgeons were not involved in data abstraction. Relative and absolute risk reductions with 95% confidence intervals (CIs) as well as a Kaplan-Meier survival curve with a Cox proportional hazard model were used to evaluate survival adjusting for significant covariates. The number needed to harm is calculated as the number needed to treat. It is the reciprocal of the absolute risk reduction or production by an intervention.RESULTS: The cumulative infection-free survival rate of TKAs at 2 years or longer was worse when PJI surgery was performed before referral to a tertiary center (80%; 95% CI, 69%-87%) compared with when no PJI surgery was performed before referral (94%; 95% CI, 87%-98%; log-rank test p = 0.006). Additionally, PJI surgery before referral resulted in a lower likelihood of causative microorganism identification (52 of 75 [69%]) compared with patients having surgery at the tertiary center (77 of 88 [88%]; odds ratio, 2.71; 95% CI, 1.28-4.70; p = 0.006). With regard to the infection-free survival rate of TKAs, the number needed to harm was 7.0 (95% CI, 4.1-22.5), meaning the referral of less than seven patients to a tertiary care center for definitive surgical management of PJI before intervention at the referring hospital prevents one infection-related failure. With regard to the culture negativity in PJI, the number needed to harm was 5.5 (95% CI, 3.3-16.7), meaning the referral of less than six patients to a tertiary care institution for PJI before surgery at the outside hospital prevents the diagnosis of one culture-negative infection.CONCLUSIONS: Surgical treatment of a PJI before referral for subspecialty surgical management increases the risk of failure of subsequent surgical management. The prevalence of culture-negative PJI was much higher if surgery was attempted before referral to a tertiary care center when compared with referral before treatment. This suggests that surgical treatment of PJI before referral to a treating center with specialized expertise in PJI compromises the infection-free survival and impacts infecting organism isolation.LEVEL OF EVIDENCE: Level III, therapeutic study.

  View details for PubMedID 30179927

• Proximal Femoral Shape Changes the Risk of a Leg Length Discrepancy After Primary Total Hip Arthroplasty. The Journal of arthroplasty Lim, Y. W., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018

  Abstract

  BACKGROUND: To evaluate how canal morphology affects the technical aspects of total hip arthroplasty, we investigated the effects of femoral cortical index (FCI) on the re-establishment of leg length at the conclusion of surgery.METHODS: We retrospectively reviewed age, gender, body mass index, and radiographs of 516 patients with osteoarthritis or osteonecrosis who underwent unilateral cementless primary total hip arthroplasty between 2008 and 2015. Patients were divided into level of FCI and leg length discrepancy (LLD). Each cohort was compared in terms of demographics and LLD. One-way analysis of variance and Kruskal-Wallis test were used.RESULTS: The mean FCI and LLD were 0.6 ± 0.1 and 3.5 ± 6.3 mm, respectively. Utilization of an extended offset stem was highest with Dorr type A and B hips (P= .001). High FCI increased the risk of lengthening (P= .017) and low FCI increased the risk of shortening (P= .005).CONCLUSION: A high FCI increases the probability of a leg length increase and a low FCI increases the probability of a leg length decrease. Surgeons might consider informing patients in advance of possible variation in leg length depending on the patients' proximal femoral shape and bony quality.

  View details for PubMedID 30173942

• NFkappaB sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles. Journal of biomedical materials research. Part A Lin, T., Kohno, Y., Huang, J., Romero-Lopez, M., Pajarinen, J., Maruyama, M., Nathan, K., Yao, Z., Goodman, S. B. 2018

  Abstract

  Total joint replacement is a highly effective treatment for patients with end-stage arthritis. Proinflammatory macrophages (M1) mediate wear particle-associated inflammation and bone loss. Anti-inflammatory macrophages (M2) help resolve tissue damage and favor bone regeneration. Mesenchymal stem cell (MSC)-based therapy mitigates the M1 dominated inflammatory reaction and favorably modulates the bone remodeling process. In the current study, the immunomodulating ability of (1) unmodified MSCs, (2) MSCs preconditioned by NFkappaB stimulating ligands [lipopolysaccharide (LPS) plus TNFalpha], and (3) genetically modified MSCs that secrete IL-4 as a response to NFkappaB activation (NFkappaB-IL4) was compared in a macrophage/MSC co-culture system. Sterile or LPS-contaminated ultra-high molecular weight polyethylene particles were used to induce the proinflammatory responses in the macrophages. Contaminated particles induced M1 marker expression (TNFalpha, IL1beta, and iNOS), while NFkappaB-IL4 MSCs modulated the macrophages from an M1 phenotype into a more favorable M2 phenotype (Arginase 1/Arg 1 and CD206 high). The IL4 secretion by NFkappaB-IL4 MSCs was significantly induced by the contaminated particles. The induction of Arg 1 and CD206 in macrophages via the preconditioned or naive MSCs was negligible when compared with NFkappaB-IL4 MSC. Our findings indicated that NFkappaB-IL4 MSCs have the "on-demand" immunomodulatory ability to mitigate wear particle-associated inflammation with minimal adverse effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018.

  View details for PubMedID 30084534

• Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur. Cytotherapy Lin, T., Pajarinen, J., Kohno, Y., Maruyama, M., Romero-Lopez, M., Huang, J., Nathan, K., Khan, T. N., Yao, Z., Goodman, S. B. 2018

  Abstract

  BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.METHODS: Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFkappaB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model.RESULTS: The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5 * 106) and low (0.5 * 106) cell-injected groups. Injection of 2.5 * 106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5 * 106 constitutive IL-4 or NFkappaB-sensing IL-4-secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFkappaB-sensing IL-4-secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)alpha and IL-1beta secretion were observed between the MSC-transplanted and control groups in the explant culture.DISCUSSION: Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4-secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.

  View details for PubMedID 30077567

• Transplanted interleukin-4-secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur CYTOTHERAPY Lin, T., Pajarinen, J., Kohno, Y., Maruyama, M., Romero-Lopez, M., Huang, J., Nathan, K., Khan, T. N., Yao, Z., Goodman, S. B. 2018; 20 (8): 1028–36

  View details for DOI 10.1016/j.jcyt.2018.06.009

  View details for Web of Science ID 000443716400005

• Systematic characterization of 3D-printed PCL/beta-TCP scaffolds for biomedical devices and bone tissue engineering: Influence of composition and porosity JOURNAL OF MATERIALS RESEARCH Bruyas, A., Lou, F., Stahl, A. M., Gardner, M., Maloney, W., Goodman, S., Yang, Y. 2018; 33 (14): 1948–59

  View details for DOI 10.1557/jmr.2018.112

  View details for Web of Science ID 000440179300003

• Systematic characterization of 3D-printed PCL/β-TCP scaffolds for biomedical devices and bone tissue engineering: influence of composition and porosity. Journal of materials research Bruyas, A., Lou, F., Stahl, A. M., Gardner, M., Maloney, W., Goodman, S., Yang, Y. P. 2018; 33 (14): 1948-1959

  Abstract

  This work aims at providing guidance through systematic experimental characterization, for the design of 3D printed scaffolds for potential orthopaedic applications, focusing on fused deposition modeling (FDM) with a composite of clinically available polycaprolactone (PCL) and β-tricalcium phosphate (β-TCP). First, we studied the effect of the chemical composition (0% to 60% β-TCP/PCL) on the scaffold's properties. We showed that surface roughness and contact angle were respectively proportional and inversely proportional to the amount of β-TCP, and that degradation rate increased with the amount of ceramic. Biologically, the addition of β-TCP enhanced proliferation and osteogenic differentiation of C3H10. Secondly, we systematically investigated the effect of the composition and the porosity on the 3D printed scaffold mechanical properties. Both an increasing amount of β-TCP and a decreasing porosity augmented the apparent Young's modulus of the 3D printed scaffolds. Third, as a proof-of-concept, a novel multi-material biomimetic implant was designed and fabricated for potential disk replacement.

  View details for DOI 10.1557/jmr.2018.112

  View details for PubMedID 30364693

  View details for PubMedCentralID PMC6197810

• Low intrapatient variability of histomorphological findings in periprosthetic tissues from revised metal/ceramic on polyethylene joint arthroplasties JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Vaculova, J., Gallo, J., Hurnik, P., Motyka, O., Goodman, S. B., Dvorackova, J. 2018; 106 (5): 2008–18

  Abstract

  The type of tissue response to implant by-products can be determined by examination of periprosthetic tissues. However, little is known about the most suitable location for tissue sampling. The main goal of this study was to evaluate the extent of variability in tissue response in relation to location of tissue sampling, implant fixation, age and sex in total joint arthroplasties with metal-on-polyethylene or ceramic-on-polyethylene bearing pairs. We processed 236 histology slides from 21 patients and focused on the association between the location of tissue samples and histological features. The presence of the synovial hyperplasia showed a significant association with the particular sampling site. A higher density of high endothelial cell venules was seen in the samples from around the joint, and polyethylene particles were more abundant in noncemented TJA but both findings did not show statistically significant association with the sampling site. The results showed a relatively small variance in the tissue response to prosthetic by-products among tissues sampled from the same patient. Our findings indicate that tissue samples retrieved from similar distance from around the TJA during the revision operation show comparable results of histological analysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2008-2018, 2018.

  View details for DOI 10.1002/jbm.b.33990

  View details for Web of Science ID 000435443500037

  View details for PubMedID 29044940

• The biological basis for concentrated iliac crest aspirate to enhance core decompression in the treatment of osteonecrosis INTERNATIONAL ORTHOPAEDICS Goodman, S. B. 2018; 42 (7): 1705–9

  View details for DOI 10.1007/s00264-018-3830-1

  View details for Web of Science ID 000436405000036

• Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? INTERNATIONAL ORTHOPAEDICS Larson, E., Jones, L. C., Goodman, S. B., Koo, K., Cui, Q. 2018; 42 (7): 1723–28

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a devastating condition affecting relatively young patients whereby the femoral head is necrotic, resulting in significant pain, articular surface collapse, and eventual osteoarthritis. This condition has been highly associated with chronic steroid use, alcoholism, and hip trauma, as well as other less common conditions. Without intervention, this condition has a high likelihood of progressing and developing into end-stage osteoarthritis. Unfortunately, ONFH is difficult to diagnose on plain radiographs in the early stages of the disease, and often requires more advanced imaging modalities such as MRI in order to fully assess for early degeneration. Providers, therefore, must have a high index of suspicion when a younger patient presents with hip pain and negative X-rays. Unfortunately, in patients whose femoral heads have already collapsed, joint-preserving procedures are not effective, and total hip arthroplasty remains the most reliable long-term treatment. Multiple treatments have been pursued to address osteonecrosis in patients whose femoral head have not yet collapsed, but the results of these treatments are mixed. The most promising of these interventions to date is core decompression with the use of concentrated bone marrow aspirate to improve the healing potential of the femoral head. Further studies including randomized clinical trials are necessary in order to assess the effectiveness of this therapy, the best possible source of cells and the best method of implantation in order to further improve results in those with pre-collapse ONFH.

  View details for PubMedID 29619500

• Effect of Computer Navigation on Complication Rates Following Unicompartmental Knee Arthroplasty. The Journal of arthroplasty Chona, D., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018

  Abstract

  BACKGROUND: We evaluated whether the complication and revision rates of unicompartmental knee arthroplasty (UKA) performed with intraoperative computer-based navigation differ from standard UKAs performed without intraoperative computer-based navigation.METHODS: A Medicare database containing administrative claims data from 2005 to 2014 was queried. Patients who underwent a single UKA and had a minimum of 2 years of follow-up were included in the study. Data from 1025 UKAs performed with navigation were compared against 9228 age and gender-matched UKAs performed without it. Postoperative complications were identified using International Classification of Diseases, Ninth Revision, codes and evaluated at 30 days, 90 days, and 2 years.RESULTS: Orthopedic complications after UKA are rare, and the use of navigation did not affect the rate of conversion to total knee arthroplasty at 2-year follow-up (3.8% in navigated UKAs vs 4.7% in standard UKAs, P= .218). There were also no significant differences in the rates of knee arthrotomy at 2-year follow-up (1.3% in navigated UKAs vs 1.6% in standard UKAs, P= .379). The rates of deep vein thrombosis at 90-day follow-up did not significantly differ between the 2 groups (1.4% in navigated UKAs vs 2.0% in standard UKAs, P= .157).CONCLUSION: This is one of the first studies to use a large cohort to compare outcomes in computer-assisted surgery-UKA against standard UKAs without navigation. The results, particularly that there was not a difference in the rate of conversion to total knee arthroplasty, are directly relevant to clinical decision-making when surgeons are considering employing navigation during UKA.

  View details for PubMedID 30033063

• Cryptotanshinone Protects Cartilage against Developing Osteoarthritis through the miR-106a-5p/GLIS3 Axis MOLECULAR THERAPY-NUCLEIC ACIDS Ji, Q., Qi, D., Xu, X., Xu, Y., Goodman, S. B., Kang, L., Song, Q., Fan, Z., Maloney, W. J., Wang, Y. 2018; 11: 170–79

  Abstract

  Cryptotanshinone (CTS) has emerged as an anti-inflammatory agent in osteoarthritis (OA). However, the molecular mechanism underlying its potent therapeutic effect on OA remains largely unknown. MicroRNAs (miRNAs) act as crucial regulators in maintaining cartilage homeostasis. To investigate whether CTS protects against developing OA through regulation of miRNAs, we examined the potential CTS-mediated miRNA molecules using microarray analysis. We found that CTS significantly promoted miR-106a-5p expression in chondrocytes. Using the OA mouse model created by anterior cruciate ligament transection, we revealed that intra-articular injection of miR-106a-5p agomir attenuated OA. In addition, miR-106a-5p inhibited GLI-similar 3 (GLIS3) production by directly targeting the 3' untranslated region. CTS promoted miR-106a-5p expression through recruitment of a member of the paired box (PAX) family of transcription factors, PAX5, to the miR-106a-5p promoter. Inhibition of PAX5 mimicked the effect of miR-106a-5p and abolished the CTS ability to regulate miR-106a-5p expression. In OA patients, miR-106-5p is downregulated which is accompanied by downregulation of PAX5 and upregulation of GLIS3. Collectively, these data highlight that the PAX5/miR-106a-5p/GLIS3 axis acts as a novel pleiotropic regulator in CTS-mediated OA cartilage protection, suggesting that miR-106a-5p and PAX5 activation and GLIS3 inhibition might be useful and attractive for therapeutic strategies to treat OA patients.

  View details for PubMedID 29858052

• Protocol-Driven Revision for Stiffness After Total Knee Arthroplasty Improves Motion and Clinical Outcomes. The Journal of arthroplasty Hug, K. T., Amanatullah, D. F., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2018

  Abstract

  BACKGROUND: Stiffness after revision total knee arthroplasty (TKA) is a difficult problem without a well-defined treatment algorithm. The purpose of this study was to evaluate the results of revision TKA for stiffness within the context of differential component replacement.METHODS: Consecutive patients who underwent revision TKA were retrospectively identified and included those who received debridement and polyethylene liner exchange alone, revision of only one of the femoral or tibial fixed components, or revision of all components. Preoperative and postoperative range of motion and Knee Society score (KSS) were collected.RESULTS: Sixty-nine knees were included in the study group with a mean follow-up of 43 months (range, 12-205 months). The mean prerevision flexion contracture of 17° improved to 5° after surgical intervention (P < .001). Similarly, mean flexion and motion arc improved from 70° to 92° and from 53° to 87°, respectively (P < .001). Mean KSS knee scores improved from 42 to 70 and KSS function scores improved from 41 to 68 (P < .001). Mean arc of motion improved by 45° in patients who underwent complete component revision, 32° with component retention, and 29° with single component revision (P= .046). KSS knee scores improved by 34, 25, and 28 points in these respective groups (P= .049). KSS function scores improved by 33, 27, and 25 points (P= .077).CONCLUSION: Revision surgery with or without component revision can improve motion and function in patients with stiffness after TKA. Complete component revision may offer the largest improvements in these outcome measures in properly selected patients.

  View details for DOI 10.1016/j.arth.2018.05.013

  View details for PubMedID 29859726

• miR-223-3p Inhibits Human Osteosarcoma Metastasis and Progression by Directly Targeting CDH6 MOLECULAR THERAPY Ji, Q., Xu, X., Song, Q., Xu, Y., Tai, Y., Goodman, S. B., Bi, W., Xu, M., Jiao, S., Maloney, W. J., Wang, Y. 2018; 26 (5): 1299–1312

  Abstract

  Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.

  View details for PubMedID 29628305

• Are New Technologies Being Introduced and Adopted Appropriately in Orthopedic Practice? ORTHOPEDICS Goodman, S. B. 2018; 41 (3): 126–27

  View details for DOI 10.3928/01477447-20180501-05

  View details for Web of Science ID 000432834800025

  View details for PubMedID 29767808

• Obesity Is Independently Associated With Early Aseptic Loosening in Primary Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Goodnough, L. H., Finlay, A. K., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018; 33 (3): 882–86

  Abstract

  Obesity affects millions of patients in the United States and is associated with several complications after total hip arthroplasty (THA). The effect of obesity on the rate and mode of primary THA failure remains poorly understood, especially given other potentially confounding patient characteristics. We hypothesized that, among patients with a failed primary THA, obesity is independently associated with aseptic loosening and a higher rate of early revision.Six hundred eighty-four consecutive cases with failed THA referred to a single academic center for revision during a 10-year period were retrospectively reviewed. Multivariate logistic regression analysis was used to test the independent association between obesity and the timing as well as cause of THA failure.The rate of primary THA failure before 5 years was 48.8% in obese and 37.1% in nonobese patients (odds ratio [OR] = 1.57, P = .010). Primary THA failure before 5 years was more likely with increasing body mass index (BMI) (BMI: 35-40 kg/m2, OR = 2.31, P = .008; BMI >40 kg/m2, OR = 2.51, P = .049). The rate of primary THA failure for aseptic loosening before 5 years was 30% in obese and 18% in nonobese patients (OR = 1.88, P = .023). Obesity was not a risk for revision for infection, whereas an American Society of Anesthesiologists class ≥3 was independently associated with primary THA failure for infection (OR = 2.33, P < .001).Among patients with a failed THA, comorbidities may account for the risk of revision due to infection in obese patients. Obesity is independently associated with early primary THA failure for aseptic loosening.

  View details for DOI 10.1016/j.arth.2017.09.069

  View details for Web of Science ID 000425893000046

  View details for PubMedID 29089226

• Customized, degradable, functionally graded scaffold for potential treatment of early stage osteonecrosis of the femoral head JOURNAL OF ORTHOPAEDIC RESEARCH Kawai, T., Shanjani, Y., Fazeli, S., Behn, A. W., Okuzu, Y., Goodman, S. B., Yang, Y. P. 2018; 36 (3): 1002–11

  Abstract

  Osteonecrosis of the femoral head (ONFH) is a debilitating disease that results in progressive collapse of the femoral head and subsequent degenerative arthritis. Few treatments provide both sufficient mechanical support and biological cues for regeneration of bone and vascularity when the femoral head is still round and therefore salvageable. We designed and 3D printed a functionally graded scaffold (FGS) made of polycaprolactone (PCL) and β-tricalcium phosphate (β-TCP) with spatially controlled porosity, degradation, and mechanical strength properties to reconstruct necrotic bone tissue in the femoral head. The FGS was designed to have low porosity segments (15% in proximal and distal segments) and a high porosity segment (60% in middle segment) according to the desired mechanical and osteoconductive properties at each specific site after implantation into the femoral head. The FGS was inserted into a bone tunnel drilled in rabbit femoral neck and head, and at 8 weeks after implantation, the tissue formation as well as scaffold degradation was analyzed. Micro-CT analysis demonstrated that the FGS-filled group had a significantly higher bone ingrowth ratio compared to the empty-tunnel group, and the difference was higher at the distal low porosity segments. The in vivo degradation rate of the scaffold was higher in the proximal and distal segments than in the middle segment. Histological analysis of both non-decalcified and calcified samples clearly indicated new bone ingrowth and bone marrow-containing bone formation across the FGS. A 3D printed PCL-β-TCP FGS appears to be a promising customized resorbable load-bearing implant for treatment of early stage ONFH. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1002-1011, 2018.

  View details for PubMedID 28782831

• The biological basis for concentrated iliac crest aspirate to enhance core decompression in the treatment of osteonecrosis. International orthopaedics Goodman, S. B. 2018

  Abstract

  Core decompression is a surgical procedure that is capable of salvaging the patient's own natural joint, if the operation is performed in the early stages of osteonecrosis, in which the articular surface has not collapsed. The addition of concentrated cells, aspirated from the iliac crest, to the core tract has been shown to enhance the viability of the femoral head, although large, prospective, randomized, blinded multicentre studies are lacking. The rationale for adding these cells to the core decompression tract is to provide osteoprogenitor and vascular progenitor cells to the area of decompressed dead bone, in order to facilitate tissue regeneration and repair. It has become increasingly evident that vast discrepancies exist in different series in regard to the criteria for patient selection, the surgical technique of core decompression, the methods for harvesting, processing, and injecting the cells, and the methodology for determining success or failure in a specific patient cohort. This paper reviews the salient points relevant to the treatment of osteonecrosis by core decompression with addition of concentrated iliac crest aspirates and poses important questions regarding the future successful application of this technique.

  View details for PubMedID 29435623

• Editorial Comment: 2017 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2018; 476 (2): 214–15

  View details for PubMedID 29529649

• Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel. Monoclonal antibodies in immunodiagnosis and immunotherapy Suzuki, T., Takakubo, Y., Oki, H., Liu, X., Honma, R., Naganuma, Y., Goodman, S. B., Kaneko, M. K., Kato, Y., Takagi, M. 2018; 37 (1): 12–19

  Abstract

  Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

  View details for PubMedID 29377768

• Particle disease really does exist An evidence based rebuttal to Dr. Mjoberg's opinion letter ACTA ORTHOPAEDICA Pajarinen, J., Gallo, J., Takagi, M., Goodman, S. B. 2018; 89 (1): 133–36

  View details for PubMedID 29143557

• Mesenchymal stem cell-macrophage crosstalk and bone healing. Biomaterials Pajarinen, J., Lin, T., Gibon, E., Kohno, Y., Maruyama, M., Nathan, K., Lu, L., Yao, Z., Goodman, S. B. 2018

  Abstract

  Recent research has brought about a clear understanding that successful fracture healing is based on carefully coordinated cross-talk between inflammatory and bone forming cells. In particular, the key role that macrophages play in the recruitment and regulation of the differentiation of mesenchymal stem cells (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies have comprehensively demonstrated that fractures do not heal without the direct involvement of macrophages. Yet the exact mechanisms by which macrophages contribute to bone regeneration remain to be elucidated. Macrophage-derived paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles; however the relative importance of inflammatory (M1) and tissue regenerative (M2) macrophages in guiding MSC differentiation along the osteogenic pathway remains poorly understood. In this review, we summarize the current understanding of the interaction of macrophages and MSCs during bone regeneration, with the emphasis on the role of macrophages in regulating bone formation. The potential implications of aging to this cellular cross-talk are reviewed. Emerging treatment options to improve facture healing by utilizing or targeting MSC-macrophage crosstalk are also discussed.

  View details for PubMedID 29329642

• Implant-Associated Bacterial Biofilm and Quorum Sensing in Periprosthetic Joint Infections. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Mooney, J. A., Pridgen, E. M., Manasherob, R. n., Suh, G. n., Blackwell, H. E., Barron, A. E., Bollyky, P. L., Goodman, S. B., Amanatullah, D. F. 2018

  Abstract

  Periprosthetic joint infection (PJI) continues to be a common complication after total knee arthroplasty and total hip arthroplasty leading to severe morbidity and mortality. With an aging population and increasing prevalence of total joint replacement procedures, the burden of PJI will be felt not only by individual patients, but in increased healthcare costs. Current treatment of PJI is inadequate resulting in incredibly high failure rates. This is believed to be largely mediated by the presence of bacterial biofilms. These polymicrobial bacterial colonies form within secreted extracellular matrices, adhering to the implant surface and local tissue. The biofilm architecture is believed to play a complex and critical role in a variety of bacterial processes including nutrient supplementation, metabolism, waste management, and antibiotic and immune resistance. The establishment of these biofilms relies heavily on the quorum sensing communication systems utilized by bacteria. Early stage research into disrupting bacterial communication by targeting quorum sensing show promise for future clinical applications. However, prevention of the biofilm formation via early forced induction of the biofilm forming process remains yet unexplored. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29663554

• Corrigendum to Outcome of 4 Surgical Treatments for Wear and Osteolysis of Cementless Acetabular Components [The Journal of Arthroplasty 32 (2017) 2799-2805]. The Journal of arthroplasty Narkbunnam, R., Amanatullah, D. F., Electricwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2018; 33 (1): 308

  View details for DOI 10.1016/j.arth.2017.10.001

  View details for PubMedID 29107500

• Production of GFP and Luciferase-Expressing Reporter Macrophages for In Vivo Bioluminescence Imaging REPORTER GENE IMAGING: METHODS AND PROTOCOLS Pajarinen, J., Lin, T., Goodman, S. B., Dubey, P. 2018; 1790: 99–111

  View details for DOI 10.1007/978-1-4939-7860-1_8

  View details for Web of Science ID 000448886300009

• Outcome of 4 Surgical Treatments for Wear and Osteolysis of Cementless Acetabular Components (vol 32, pg 2799, 2017) JOURNAL OF ARTHROPLASTY Narkbunnam, R., Amanatullah, D. F., Electricwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2018; 33 (1): 308

  View details for DOI 10.1016/j.arth.2017.10.001

  View details for Web of Science ID 000418761100061

• Metal-on-metal total hip arthroplasty is not associated with cardiac disease BONE & JOINT JOURNAL Goodnough, L. H., Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2018; 100B (1): 28–32

  Abstract

  Many case reports and small studies have suggested that cobalt ions are a potential cause of cardiac complications, specifically cardiomyopathy, after metal-on-metal (MoM) total hip arthroplasty (THA). The impact of metal ions on the incidence of cardiac disease after MoM THA has not been evaluated in large studies. The aim of this study was to compare the rate of onset of new cardiac symptoms in patients who have undergone MoM THA with those who have undergone metal-on-polyethylene (MoP) THA.Data were extracted from the Standard Analytics Files database for patients who underwent MoM THA between 2005 and 2012. Bearing surface was selected using International Classification of Diseases ninth revision codes. Patients with a minimum five-year follow-up were selected. An age and gender-matched cohort of patients who underwent MoP THA served as a comparison group. New diagnoses of cardiac disease were collected during the follow-up period. Comorbidities and demographics were identified and routine descriptive statistics were used.We identified 29 483 patients who underwent MoM THA and 24 175 matched patients who underwent MoP THA. Both groups had a mean Charlson comorbidity index score of 4. There were no statistically significant differences in 30 of 31 pre-existing comorbidities. Patients undergoing MoM THA had a slightly lower incidence of cardiac failure compared with those undergoing MoP THA at three years (6.60% versus 7.06%, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.87 to 0.99) and four years (8.73% versus 9.49%, OR 0.91, 95% CI 0.86 to 0.97) postoperatively, with no difference in the incidence of new cardiac failure in between the groups at five years. There was no statistically significant difference in the incidence of arrhythmia, myocardial infarction and cardiomyopathy at any time between the two groups.MoM THA is not associated with cardiac complications. Initial reports may have represented individual instances of cardiac disease in patients with a failing MoM articulation rather than an emerging epidemiological trend. Cite this article: Bone Joint J 2018;100-B:28-32.

  View details for PubMedID 29305447

• Production of GFP and Luciferase-Expressing Reporter Macrophages for In Vivo Bioluminescence Imaging. Methods in molecular biology (Clifton, N.J.) Pajarinen, J., Lin, T., Goodman, S. B. 2018; 1790: 99–111

  Abstract

  Macrophages have emerged as crucial regulators of tissue homeostasis, inflammation, and tissue regeneration. In vivo bioluminescence imaging could offer a powerful tool to study many poorly understood aspects of macrophage biology. Thus, we recently developed a straightforward method for the production of large numbers of green fluorescent protein (GFP) and firefly luciferase (fLUC)-expressing reporter macrophages for various in vivo bioluminescence imaging applications. Lentivirus vector containing the GFP/fLUC reporter gene is produced and mouse bone marrow macrophages are isolated following established protocols. Macrophages are then exposed to the lentivirus in the presence of 10muM cyclosporine for 24h. After a 24-h recovery period, the transduction is repeated. Three days after the second infection the cells are ready to be used in vivo. Following this cyclosporine-mediated double infection strategy up to 60% of the macrophages express GFP in flow cytometry. The macrophages maintain their ability to polarize to M1 and M2 phenotypes and, when injected to the systemic circulation of a mouse model, reporter cells are both easily detectable with BLI and migrate to a local site of inflammation. These GFP/fLUC-expressing reporter macrophages could prove to be useful tools to study the role of macrophages in health and disease.

  View details for PubMedID 29858786

• Perioperative Pain Management for Total Knee Arthroplasty: Need More Focus on the Forest and Less on the Trees. Anesthesiology Webb, C. A., Madison, S. n., Goodman, S. B., Mariano, E. R., Horn, J. L. 2018; 128 (2): 420–21

  View details for PubMedID 29337751

• Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis STEM CELL RESEARCH & THERAPY Lin, T., Pajarinen, J., Nabeshima, A., Lu, L., Nathan, K., Jamsen, E., Yao, Z., Goodman, S. B. 2017; 8

  View details for DOI 10.1186/s13287-017-0730-z

  View details for Web of Science ID 000417519200003

• Preconditioning of murine mesenchymal stem cells synergistically enhanced immunomodulation and osteogenesis. Stem cell research & therapy Lin, T., Pajarinen, J., Nabeshima, A., Lu, L., Nathan, K., Jämsen, E., Yao, Z., Goodman, S. B. 2017; 8 (1): 277

  Abstract

  Mesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation.In the current study, we developed a novel preconditioning strategy for MSCs using LPS plus TNF-α to optimize the immunomodulating ability of MSCs on macrophage polarization.Preconditioned MSCs enhanced anti-inflammatory M2 macrophage marker expression (Arginase 1 and CD206) and decreased inflammatory M1 macrophage marker (TNF-α/IL-1Ra) expression using an in-vitro coculture model. Immunomodulation of MSCs on macrophages was significantly increased compared to the combination of IFN-γ plus TNF-α or single treatment controls. Increased osteogenic differentiation including alkaline phosphate activity and matrix mineralization was only observed in the LPS plus TNF-α preconditioned MSCs. Mechanistic studies showed that increased prostaglandin E2 (PGE2) production was associated with enhanced Arginase 1 expression. Selective cyclooxygenase-2 inhibition by Celecoxib decreased PGE2 production and Arginase 1 expression in cocultured macrophages.The novel preconditioned MSCs have increased immunomodulation and bone regeneration potential and could be applied to the treatment of inflammatory bone disorders including periprosthetic osteolysis, fracture healing/nonunions, and osteonecrosis.

  View details for DOI 10.1186/s13287-017-0730-z

  View details for PubMedID 29212557

  View details for PubMedCentralID PMC5719931

• Tissue-Invasive T Cells in Rheumatoid Arthritis Weyand, C. M., Shen, Y., Li, Y., Matteson, E. L., Goodman, S., Goronzy, J. WILEY. 2017

  View details for Web of Science ID 000411824106206

• Patient Satisfaction After Total Knee Arthropliasty A Realistic or Imaginary Goal? ORTHOPEDIC CLINICS OF NORTH AMERICA Gibon, E., Goodman, M. J., Goodman, S. B. 2017; 48 (4): 421-+

  Abstract

  This article summarizes the current literature regarding patient satisfaction after total knee arthroplasty. In 10% to 15% of cases, the operation has not met the patients' expectations. The causes of this dissatisfaction are multifactorial, and include patient-related factors, details related to the surgical procedure and prosthesis chosen, perioperative factors, and factors associated with nursing and general medical care. However, surgeons must bear the brunt of patients' dissatisfaction. This dissatisfaction erodes the doctor-patient relationship, and may have implications in an emerging health care economy in which doctors and hospitals are reimbursed based on both clinical outcome and patient satisfaction.

  View details for PubMedID 28870303

• Response to Letter to the Editor on "Weight Gain After Primary Total Knee Arthroplasty is Associated With Accelerated Time to Revision for Aseptic Loosening" JOURNAL OF ARTHROPLASTY Lim, C. T., Goodman, S. B., Huddleston, J. I., Harris, A. S., Bhowmick, S., Maloney, W. J., Amanatullah, D. F. 2017; 32 (10): 3258

  View details for PubMedID 28705544

• An evidence-based guide to the treatment of osteonecrosis of the femoral head BONE & JOINT JOURNAL Chughtai, M., Piuzzi, N. S., Khlopas, A., Jones, L. C., Goodman, S. B., Mont, M. A. 2017; 99B (10): 1267–79

  Abstract

  Non-traumatic osteonecrosis of the femoral head is a potentially devastating condition, the prevalence of which is increasing. Many joint-preserving forms of treatment, both medical and surgical, have been developed in an attempt to slow or reverse its progression, as it usually affects young patients. However, it is important to evaluate the best evidence that is available for the many forms of treatment considering the variation in the demographics of the patients, the methodology and the outcomes in the studies that have been published, so that it can be used effectively. The purpose of this review, therefore, was to provide an up-to-date, evidence-based guide to the management, both non-operative and operative, of non-traumatic osteonecrosis of the femoral head. Cite this article: Bone Joint J 2017;99-B:1267-79.

  View details for PubMedID 28963146

• miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14 CELL DEATH & DISEASE Ji, Q., Xu, X., Li, L., Goodman, S. B., Bi, W., Xu, M., Xu, Y., Fan, Z., Maloney, W. J., Ye, Q., Wang, Y. 2017; 8: e3103

  Abstract

  Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.

  View details for PubMedID 29022909

• Inflammation, ageing, and bone regeneration JOURNAL OF ORTHOPAEDIC TRANSLATION Gibon, E., Lu, L. Y., Nathan, K., Goodman, S. B. 2017; 10: 28–35

  Abstract

  Bone healing involves complex biological pathways and interactions among various cell types and microenvironments. Among them, the monocyte-macrophage-osteoclast line-age and the mesenchymal stem cell-osteoblast lineage are critical, in addition to an initial inflammatory microenvironment. These cellular interactions induce the necessary inflammatory milieu and provide the cells for bone regeneration and immune modulation. Increasing age is accompanied with a rise in the basal state of inflammation, potentially impairing osteogenesis.Translational research has shown multiple interactions between inflammation, ageing, and bone regeneration. This review presents recent, relevant considerations regarding the effects of inflammation and ageing on bone healing.

  View details for PubMedID 29094003

• Inflammation and its resolution and the musculoskeletal system JOURNAL OF ORTHOPAEDIC TRANSLATION Gallo, J., Raska, M., Kriegova, E., Goodman, S. B. 2017; 10: 52–67

  Abstract

  Inflammation, an essential tissue response to extrinsic/intrinsic damage, is a very dynamic process in terms of complexity and extension of cellular and metabolic involvement. The aim of the inflammatory response is to eliminate the pathogenic initiator with limited collateral damage of the inflamed tissue, followed by a complex tissue repair to the preinflammation phenotype. Persistent inflammation is a major contributor to the pathogenesis of many musculoskeletal diseases including ageing-related pathologies such as osteoporosis, osteoarthritis, and sarcopaenia. Understanding the mechanisms of inflammation and its resolution is therefore critical for the development of effective regenerative, and therapeutic strategies in orthopaedics.

  View details for PubMedID 28781962

• Inflammation and the musculoskeletal system JOURNAL OF ORTHOPAEDIC TRANSLATION Goodman, S. B., Qin, L. 2017; 10: A1–A2

  View details for PubMedID 29662763

• Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements JOURNAL OF ORTHOPAEDIC TRANSLATION Takagi, M., Takakubo, Y., Pajarinen, J., Naganuma, Y., Oki, H., Maruyama, M., Goodman, S. B. 2017; 10: 68–85

  Abstract

  The innate immune sensors, Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), can recognize not only exogenous pathogen-associated molecular patterns (PAMPs), but also endogenous molecules created upon tissue injury, sterile inflammation, and degeneration. Endogenous ligands are called damage-associated molecular patterns (DAMPs), and include endogenous molecules released from activated and necrotic cells as well as damaged extracellular matrix. TLRs and NLRs can interact with various ligands derived from PAMPs and DAMPs, leading to activation and/or modulation of intracellular signalling pathways. Intensive research on the innate immune sensors, TLRs and NLRs, has brought new insights into the pathogenesis of not only various infectious and rheumatic diseases, but also aseptic foreign body granuloma and septic inflammation of failed total hip replacements (THRs). In this review, recent knowledge is summarized on the innate immune system, including TLRs and NLRs and their danger signals, with special reference to their possible role in the adverse local host response to THRs.

  View details for PubMedID 29130033

• Continuous Femoral Nerve Catheters Decrease Opioid-Related Side Effects and Increase Home Disposition Rates Among Geriatric Hip Fracture Patients. Journal of orthopaedic trauma Arsoy, D., Gardner, M. J., Amanatullah, D. F., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Bishop, J. A. 2017; 31 (6): e186-e189

  Abstract

  To evaluate the effect of continuous femoral nerve catheter (CFNC) for postoperative pain control in geriatric proximal femur fractures compared with standard analgesia (SA) treatment.Retrospective comparative study.Academic Level 1 trauma center.We retrospectively identified 265 consecutive geriatric hip fracture patients who underwent surgical treatment.One hundred forty-nine patients were treated with standard analgesia without nerve catheter whereas 116 patients received an indwelling CFNC.Daily average preoperative and postoperative pain scores, daily morphine equivalent consumption, opioid-related side effects and discharge disposition.Patients with CFNC patients reported lower average pain scores preoperatively (1.9 ± 1.7 for CFNC vs. 4.7 ± 2 for SA; P < 0.0001), on postoperative day 1 (1.5 ± 1.6 for CFNC vs. 3 ± 1.7 for SA; P < 0.0001) and postoperative day 2 (1.2 ± 1.5 for CFNC vs. 2.6 ± 2.1 for SA; P < 0.0001). CFNC group consumed 39% less morphine equivalents on postoperative day 1 (4.4 ± 5.8 mg for CFNC vs. 7.2 ± 10.8 mg for SA; P = 0.005) and 50% less morphine equivalent on postoperative day 2 (3.4 ± 4.4 mg for CFNC vs. 6.8 ± 13 mg for SA; P = 0.105). Patients with CFNC had a lower rate of opioid-related side effects compared with patients with SA (27.5% for CFNC vs. 47% for SA; P = 0.001). More patients with CFNC were discharged to home with or without health services than patients with SA (15% for CFNC vs. 6% for SA; P = 0.023).Continuous femoral nerve catheter decreased daily average patient-reported pain scores, narcotic consumption while decreasing the rate of opioid-related side effects. Patients with CFNC were discharged to home more frequently.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/BOT.0000000000000854

  View details for PubMedID 28538458

• The effect of desflurane versus propofol anesthesia on postoperative delirium in elderly obese patients undergoing total knee replacement: A randomized, controlled, double-blinded clinical trial. Journal of clinical anesthesia Tanaka, P., Goodman, S., Sommer, B. R., Maloney, W., Huddleston, J., Lemmens, H. J. 2017; 39: 17-22

  Abstract

  The goal of this study was to investigate the incidence of delirium, wake-up times and early post-operative cognitive decline in one hundred obese elderly patients undergoing total knee arthroplasty.Prospective randomized trial.Operating room, postoperative recovery area, hospital wards.100 obese patients (ASA II and III) undergoing primary total knee replacement under general anesthesia with a femoral nerve block catheter.Patients were prospectively randomized to maintenance anesthesia with either propofol or desflurane.The primary endpoint assessed by a blinded investigator was delirium as measured by the Confusion Assessment Method. Secondary endpoints were wake-up times and a battery of six different tests of cognitive function.Four of the 100 patients that gave informed consent withdrew from the study. Of the remaining 96 patients, 6 patients did not complete full CAM testing. Preoperative pain scores, durations of surgery and anesthesia, and amount of intraoperative fentanyl were not different between groups. One patient in the propofol group developed delirium compared to zero in desflurane. One patient in desflurane group developed a confused state not characterized as delirium. Fifty percent of the patients exhibited a 20% decrease in the results of at least one cognitive test on the first 2days after surgery, with no difference between groups. There were no differences in the time to emergence from anesthesia, incidence of postoperative nausea and vomiting, and length of postanesthesia care unit (PACU) stay between the two groups.In conclusion we found a low incidence of delirium but significant cognitive decline in the first 48h after surgery. In this relatively small sample size of a hundred patients there was no difference in the incidence of postoperative delirium, early cognitive outcomes, or wake up times between the desflurane or propofol group.

  View details for DOI 10.1016/j.jclinane.2017.03.015

  View details for PubMedID 28494898

• Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors? Clinical orthopaedics and related research Bala, A., Huddleston, J. I., Goodman, S. B., Maloney, W. J., Amanatullah, D. F. 2017

  Abstract

  There is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors.Using a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time?We queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate.There was a difference in the incidence of DVT at 90 days (p < 0.01). Factor Xa inhibitors (2.9%) had the lowest incidence of DVT followed by aspirin (3.0%) and enoxaparin (3.5%), and warfarin (4.8%). There was a difference in the incidence of PE at 90 days (p < 0.01). Factor Xa inhibitors (0.9%) had the lowest incidence of PE followed by enoxaparin (1.1%), aspirin (1.2%), and warfarin (1.6%). There was a difference in the incidence of postoperative anemia at 90 days (p < 0.01). Aspirin (19%) had the lowest incidence of postoperative anemia followed by warfarin (22%), enoxaparin (23%), and factor Xa inhibitors (23%). There was a difference in the incidence of a blood transfusion at 90 days (p < 0.01). Aspirin (7%) had the lowest incidence of a blood transfusion followed by factor Xa inhibitors (9%), warfarin (12%), and enoxaparin (13%). There were no differences in bleeding-related complications (p = 0.81) between the groups. Aspirin use increased at a compound annual growth rate of 30%, enoxaparin at 3%, and factor Xa inhibitors at 43%, while warfarin use decreased at a compound annual growth rate of -3%.Factor Xa inhibitors had the highest growth in utilization during our study period, followed by aspirin, when compared with enoxaparin and warfarin. When selected for the right patient, factor Xa inhibitors provided improved VTE prophylaxis compared with enoxaparin and warfarin, with a lower rate of blood transfusion. Aspirin provided comparable VTE prophylaxis compared with factor Xa inhibitors with improved VTE prophylaxis compared with enoxaparin and warfarin with the lowest risk of bleeding.Level III, therapeutic study.

  View details for DOI 10.1007/s11999-017-5394-6

  View details for PubMedID 28569372

• CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis ANNALS OF THE RHEUMATIC DISEASES Raghu, H., Lepus, C. M., Wang, Q., Wong, H. H., Lingampalli, N., Oliviero, F., Punzi, L., Giori, N. J., Goodman, S. B., Chu, C. R., Sokolove, J. B., Robinson, W. H. 2017; 76 (5)

  Abstract

  While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/CCR5 chemokine axes in OA pathogenesis.Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA. The pharmacological utility of blocking CCL2/CCR2 signalling in mouse OA was investigated using bindarit, a CCL2 synthesis inhibitor, and RS-504393, a CCR2 antagonist. Levels of monocyte chemoattractants in synovial tissues and fluids from patients with joint injuries without OA and those with established OA were investigated using a combination of microarray analyses, multiplexed cytokine assays and immunostains.Mice lacking CCL2 or CCR2, but not CCL5 or CCR5, were protected against OA with a concomitant reduction in local monocyte/macrophage numbers in their joints. In synovial fluids from patients with OA, levels of CCR2 ligands (CCL2, CCL7 and CCL8) but not CCR5 ligands (CCL3, CCL4 and CCL5) were elevated. We found that CCR2+ cells are abundant in human OA synovium and that CCR2+ macrophages line, invade and are associated with the erosion of OA cartilage. Further, blockade of CCL2/CCR2 signalling markedly attenuated macrophage accumulation, synovitis and cartilage damage in mouse OA.Our findings demonstrate that monocytes recruited via CCL2/CCR2, rather than by CCL5/CCR5, propagate inflammation and tissue damage in OA. Selective targeting of the CCL2/CCR2 system represents a promising therapeutic approach for OA.

  View details for DOI 10.1136/annrheumdis-2016-210426

  View details for Web of Science ID 000398387200022

• A Randomized Trial of Perioperative Gabapentin to Promote Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort Hah, J., Mackey, S., Efron, B., Mccue, R., Goodman, S., Curtin, C., Carroll, I. LIPPINCOTT WILLIAMS & WILKINS. 2017: 813–17

  View details for Web of Science ID 000412683000420

• Cortical Strut Allograft Support of Modular Femoral Junctions During Revision Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Lim, C. T., Amanatullah, D. F., Huddleston, J. I., Hwang, K. L., Maloney, W. J., Goodman, S. B. 2017; 32 (5): 1586-1592

  Abstract

  There is risk of junction failure when using modular femoral stems for revision total hip arthroplasty (THA), especially with loss of bone stock in the proximal femur. Using a cortical strut allograft may provide additional support of a modular femoral construct in revision THA.We reviewed prospectively gathered clinical and radiographic data for 28 revision THAs performed from 2004 to 2014 using cementless modular femoral components with cortical strut allograft applied to supplement proximal femoral bone loss: 5 (18%) were fluted taper designs and 23 (82%) were porous cylindrical designs All the patients had a Paprosky grade IIIA or greater femoral defect. The mean follow-up was 5.4 ± 3.9 years.The Harris Hip Scores improved from 26 ± 10 points preoperatively to 71 ± 10 points at final follow-up (P < .001). The Western Ontario McMaster Universities Osteoarthritis Index scores improved from 45 ± 12 points preoperatively to 76 ± 12 points at final follow-up (P < .001). Eighty-nine percent (25 hips) of all revision or conversion THAs were in place at final follow-up. Three (11%) patients underwent reoperations, 2 for infection and 1 for periprosthetic fracture. There was no statistical significant change in femoral component alignment (P = .161) at final follow-up. Mean subsidence was 1.8 ± 1.3 mm at final follow-up. Femoral diameter increased from initial postoperative imaging to final follow-up imaging by a mean of 9.1 ± 5.1 mm (P < .001) and cortical width increased by a mean of 4.5 ± 2.2 mm (P < .001). Twenty-seven hips (96%) achieved union between the cortical strut allograft and the host femur.The use of a modular femoral stem in a compromised femur with a supplementary cortical strut allgraft is safe and provides satisfactory clinical and radiological outcomes.

  View details for DOI 10.1016/j.arth.2016.12.011

  View details for Web of Science ID 000401132100033

• Use of Cortical Strut Allograft After Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Lim, C. T., Amanatullah, D. F., Huddleston, J. I., Hwang, K. L., Maloney, W. J., Goodman, S. B. 2017; 32 (5): 1599-1605

  Abstract

  Cortical strut allografts restore bone stock and improve postoperative clinical scores after revision total hip arthroplasty (THA). However, use of a cortical strut allograft is implicated in delayed healing of an extended trochanteric osteotomy (ETO). To date, there are no reports directly comparing ETO with or without cortical strut allografts.We reviewed prospectively gathered data on 50 revision THAs performed from 2004-2014 using an ETO. We compared the demographic, radiological, and clinical outcome of patients with (16 hips) and without (34 hips) cortical strut allograft after an ETO.There were no significant differences in Western Ontario McMaster Universities Osteoarthritis Index or Harris Hip Score between the ETOs with and without a cortical strut allograft. Fifteen of the ETOs (94%) with a cortical strut allograft and 31 of the ETOs (91%) without a cortical strut allograft were in situ at final follow-up (P = 1.000). A higher proportion hips with cortical strut allograft (100%, 16 patients) had preoperative Paprosky grade bone loss more than IIIA compared to those without allograft (29%, 10 patients) (P < .001). There were no differences in femoral stem subsidence (P = .207), alignment (P = .934), or migration of the osteotomized fragment (P = .171). Fourteen of the ETOs (88%) in patients with cortical strut allograft united compared to 34 ETOs (100%) in patients without allograft (P = .095).Our study shows that the use of cortical strut allograft during revision THA with ETO does not reduce the rate of union, radiological or clinical outcomes.

  View details for DOI 10.1016/j.arth.2016.12.002

  View details for Web of Science ID 000401132100035

• Radiographic scoring system for the evaluation of stability of cementless acetabular components in the presence of osteolysis BONE & JOINT JOURNAL Narkbunnam, R., Amanatullah, D. F., Electricwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2017; 99-B (5): 601-606

  Abstract

  The stability of cementless acetabular components is an important factor for surgical planning in the treatment of patients with pelvic osteolysis after total hip arthroplasty (THA). However, the methods for determining the stability of the acetabular component from pre-operative radiographs remain controversial. Our aim was to develop a scoring system to help in the assessment of the stability of the acetabular component under these circumstances.The new scoring system is based on the mechanism of failure of these components and the location of the osteolytic lesion, according to the DeLee and Charnley classification. Each zone is evaluated and scored separately. The sum of the individual scores from the three zones is reported as a total score with a maximum of 10 points. The study involved 96 revision procedures which were undertaken for wear or osteolysis in 91 patients between July 2002 and December 2012. Pre-operative anteroposterior pelvic radiographs and Judet views were reviewed. The stability of the acetabular component was confirmed intra-operatively.Intra-operatively, it was found that 64 components were well-fixed and 32 were loose. Mean total scores in the well-fixed and loose components were 2.9 (0 to 7) and 7.2 (1 to 10), respectively (p < 0.001). In hips with a low score (0 to 2), the component was only loose in one of 33 hips (3%). The incidence of loosening increased with increasing scores: in those with scores of 3 and 4, two of 19 components (10.5%) were loose; in hips with scores of 5 and 6, eight of 19 components (44.5%) were loose; in hips with scores of 7 or 8, 13 of 17 components (70.6%) were loose; and for hips with scores of 9 and 10, nine of nine components (100%) were loose. Receiver-operating-characteristic curve analysis demonstrated very good accuracy (area under the curve = 0.90, p < 0.001). The optimal cutoff point was a score of ≥ 5 with a sensitivity of 0.79, and a specificity of 0.87.There was a strong correlation between the scoring system and the probability of loosening of a cementless acetabular component. This scoring system provides a clinically useful tool for pre-operative planning, and the evaluation of the outcome of revision surgery for patients with loosening of a cementless acetabular component in the presence of osteolysis. Cite this article: Bone Joint J 2017;99-B:601-6.

  View details for DOI 10.1302/0301-620X.99B5.BJJ-2016-0968.R1

  View details for PubMedID 28455468

• Outcome of 4 Surgical Treatments for Wear and Osteolysis of Cementless Acetabular Components. journal of arthroplasty Narkbunnam, R., Amanatullah, D. F., Electriwala, A. J., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2017

  Abstract

  Loosening and periprosthetic osteolysis are some of the most common long-term complications after hip arthroplasty. The decision-making process and surgical treatment options are controversial.We retrospectively reviewed 96 acetabular revisions (91 patients) performed between 2002 and 2012, with a minimum of 2 years of follow-up and a mean of 5.7 years of follow-up. Clinical outcome was assessed using the Harris Hip Score. The size and location of osteolytic lesions were evaluated using the preoperative radiographs; healing of the defects was categorized using a standardized protocol.Thirty-three (34.4%) hips had isolated liner exchanges (ILEs), 10 (10.4%) hips had cemented liners into well-fixed shells (CLS), 45 (46.9%) hips had full acetabular revisions (FARs), and 8 (8.3%) hips had revision with a roof ring/antiprotrusio cage (RWC). All procedures showed significant improvement in Harris Hip Score after revision (P ≤ .001). Fifteen patients had moderate residual pain (pain score ≤20): 8 (24%) ILE, 3 (30%) CLS, and 4 (9%) FAR. Complete bone defect healing after grafting was lower with acetabular component retention procedures (ILE and CLS; 27%) compared with full acetabular component revision procedures (FAR and RWC; 57%). Fifteen patients underwent reoperation: 3 ILE, 1 CLS, 8 FAR, and 3 RWC.Acetabular component retention demonstrates a low risk of reoperation; however, residual pain and limited potential for bone graft incorporation are a concern. FAR is technically challenging and may have an elevated risk of reoperation; however, higher degrees of bone graft incorporation and satisfactory clinical outcome can be expected.

  View details for DOI 10.1016/j.arth.2017.04.028

  View details for PubMedID 28587888

• Mesenchymal stem cells in the aseptic loosening of total joint replacements. Journal of biomedical materials research. Part A Pajarinen, J., Lin, T., Nabeshima, A., Jämsen, E., Lu, L., Nathan, K., Yao, Z., Goodman, S. B. 2017; 105 (4): 1195-1207

  Abstract

  Peri-prosthetic osteolysis remains as the main long-term complication of total joint replacement surgery. Research over four decades has established implant wear as the main culprit for chronic inflammation in the peri-implant tissues and macrophages as the key cells mediating the host reaction to implant-derived wear particles. Wear debris activated macrophages secrete inflammatory mediators that stimulate bone resorbing osteoclasts; thus bone loss in the peri-implant tissues is increased. However, the balance of bone turnover is not only dictated by osteoclast-mediated bone resorption but also by the formation of new bone by osteoblasts; under physiological conditions these two processes are tightly coupled. Increasing interest has been placed on the effects of wear debris on the cells of the bone-forming lineage. These cells are derived primarily from multipotent mesenchymal stem cells (MSCs) residing in bone marrow and the walls of the microvasculature. Accumulating evidence indicates that wear debris significantly impairs MSC-to-osteoblast differentiation and subsequent bone formation. In this review, we summarize the current understanding of the effects of biomaterial implant wear debris on MSCs. Emerging treatment options to improve initial implant integration and treat developing osteolytic lesions by utilizing or targeting MSCs are also discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1195-1207, 2017.

  View details for DOI 10.1002/jbm.a.35978

  View details for PubMedID 27977880

• Mesenchymal stem cells homing to improve bone healing JOURNAL OF ORTHOPAEDIC TRANSLATION Lin, W., Xu, L., Zwingenberger, S., Gibon, E., Goodman, S. B., Li, G. 2017; 9: 19–27

  Abstract

  Cell therapy continues to attract growing interest as a promising approach to treat a variety of diseases. Mesenchymal stem cells (MSCs) have been one of the most intensely studied candidates for cell therapy. Since the homing capacity of MSCs is an important determinant of effective MSC-based therapy, the enhancement of homing efficiency is essential for optimizing the therapeutic outcome. Furthermore, trafficking of endogenous MSCs to damaged tissues, also referred to as endogenic stem cell homing, and the subsequent participation of MSCs in tissue regeneration are considered to be a natural self-healing response. Therefore, strategies to stimulate and reinforce the mobilisation and homing of MSCs have become a key point in regenerative medicine. The current review focuses on advances in the mechanisms and factors governing trafficking of MSCs, and the relationship between MSC mobilisation and skeletal diseases, providing insights into strategies for their potential translational implications.

  View details for PubMedID 29662796

• Total hip arthroplasty using a monobloc cementless femoral stem for patients with childhood Perthes' disease BONE & JOINT JOURNAL Lee, K. H., Jo, W., Ha, Y. C., Lee, Y. K., Goodman, S. B., Koo, K. H. 2017; 99B (4): 440-444

  Abstract

  Modular or custom-made femoral components have been preferred for total hip arthroplasty (THA) in patients with a history of Perthes' disease because of the distortion in the anatomy of the proximal femur. However, it has not been established whether a monobloc cementless stem will fit the distorted proximal femur or whether the results of the procedure are satisfactory in this group of patients.We reviewed 68 consecutive patients who had undergone THA for childhood Perthes' disease between June 2003 and December 2008. There were 35 men and 33 women with a mean age of 48 years (16 to 73) at the time of index arthroplasty. Their mean body mass index was 24.4 (18.3 to 32.9). Of the 68 hips, 32 were classified as Stulberg class III and 36 as class IV. The mean pre-operative shortening of the affected leg was 17.2 mm (5 to 34). The minimum follow-up was five years (mean 8.5 years; 5.2 to 10).An intra-operative calcar fracture occurred in eight hips (11.8%) and was successfully treated by cerclage wiring. The mean stem version was 14.6° (-2.3 to 30; standard deviation (sd) 7.3). The mean acetabular component abduction was 40.2° (23.7 to 56.0; sd 6.5) and the mean anteversion 28.3° (6.4 to 43.0; sd 7.6), respectively. The mean follow-up was 8.5 years (5.2 to 10). No dislocations occurred and no hips were revised during the course of the study. At final follow-up, the mean Harris Hip Score was 91 points (59 to 100) and the mean University of California, Los Angeles activity score was 3.2 (2 to 8).Monobloc cementless stems reliably restore the anatomy in Perthes' disease at THA without the need for custom-made or modular implants. Cite this article: Bone Joint J 2017;99-B:440-444.

  View details for DOI 10.1302/0301-620X.99B4.BJJ-2016-0259.R1

  View details for Web of Science ID 000399328900005

• Total hip arthroplasty using a monobloc cementless femoral stem for patients with childhood Perthes' disease. bone & joint journal Lee, K. H., Jo, W., Ha, Y. C., Lee, Y. K., Goodman, S. B., Koo, K. H. 2017; 99-B (4): 440-444

  Abstract

  Modular or custom-made femoral components have been preferred for total hip arthroplasty (THA) in patients with a history of Perthes' disease because of the distortion in the anatomy of the proximal femur. However, it has not been established whether a monobloc cementless stem will fit the distorted proximal femur or whether the results of the procedure are satisfactory in this group of patients.We reviewed 68 consecutive patients who had undergone THA for childhood Perthes' disease between June 2003 and December 2008. There were 35 men and 33 women with a mean age of 48 years (16 to 73) at the time of index arthroplasty. Their mean body mass index was 24.4 (18.3 to 32.9). Of the 68 hips, 32 were classified as Stulberg class III and 36 as class IV. The mean pre-operative shortening of the affected leg was 17.2 mm (5 to 34). The minimum follow-up was five years (mean 8.5 years; 5.2 to 10).An intra-operative calcar fracture occurred in eight hips (11.8%) and was successfully treated by cerclage wiring. The mean stem version was 14.6° (-2.3 to 30; standard deviation (sd) 7.3). The mean acetabular component abduction was 40.2° (23.7 to 56.0; sd 6.5) and the mean anteversion 28.3° (6.4 to 43.0; sd 7.6), respectively. The mean follow-up was 8.5 years (5.2 to 10). No dislocations occurred and no hips were revised during the course of the study. At final follow-up, the mean Harris Hip Score was 91 points (59 to 100) and the mean University of California, Los Angeles activity score was 3.2 (2 to 8).Monobloc cementless stems reliably restore the anatomy in Perthes' disease at THA without the need for custom-made or modular implants. Cite this article: Bone Joint J 2017;99-B:440-444.

  View details for DOI 10.1302/0301-620X.99B4.BJJ-2016-0259.R1

  View details for PubMedID 28385931

• Revision Hip Arthroplasty Using a Modular, Cementless Femoral Stem: Intermediate-Term Follow-Up JOURNAL OF ARTHROPLASTY Sivananthan, S., Lim, C., Narkbunnam, R., Sox-Harris, A., Huddleston, J. I., Goodman, S. B. 2017; 32 (4): 1245-1249

  Abstract

  Modular femoral stem provides flexibility in femoral reconstruction, ensuring improved "fit and fill". However, there are risks of junction failure and corrosion, as well as cost concerns in the use of modular femoral stems.We reviewed prospectively-gathered clinical and radiographic data on revision total hip arthroplasties (THAs) performed from 2001-2007 using modular, cementless femoral component performed by the 2 senior authors. Patients with a minimum follow-up of 7 years were included in this study.Sixty-four patients (68 hips) with a median age of 68 ± 14 years (range 40-92 years) at revision THA were included. The median follow-up was 11.0 ± 1.8 years (range 7-14). Harris hip score, femoral stem subsidence, and stem osseointegration were recorded. The Harris hip score improved from an average of 38.1-80.1 (P < .01). Five hips had one or more dislocations. Seven patients underwent reoperations, 3 of which did not involve the stem. Four stems required revision because of infection, recurrent dislocation, or suboptimal implant position. Survival rates for any reasons and revision for femoral stems were 90% and 94%, respectively, at the most recent follow-up. Four stems subsided more than 5 mm, but established stable osseointegration thereafter. Seven nonloose stems (10.2%) demonstrated radiolucent lines in Gruen zones 1 and 7. No complications regarding the modular junction were encountered.Modular, cementless, extensively porous-coated femoral components have demonstrated intermediate-term clinical and radiographic success. Initial distal intramedullary fixation ensures stability, and proximal modularity further maximizes fit and fill.

  View details for DOI 10.1016/j.arth.2016.10.033

  View details for Web of Science ID 000401125600036

• Pro-inflammatory M1 macrophages promote osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway. Journal of orthopaedic research Lu, L. Y., Loi, F., Nathan, K., Lin, T., Pajarinen, J., Gibon, E., Nabeshima, A., Cordova, L., Jämsen, E., Yao, Z., Goodman, S. B. 2017

  Abstract

  Bone fractures are among the most common orthopaedic problems that affect individuals of all ages. Immediately after injury, activated macrophages dynamically contribute to and regulate an acute inflammatory response that involves other cells at the injury site, including mesenchymal stem cells (MSCs). These macrophages and MSCs work in concert to modulate bone healing. In this study, we co-cultured undifferentiated M0, pro-inflammatory M1, and anti-inflammatory M2 macrophages with primary murine MSCs in vitro to determine the cross-talk between polarized macrophages and MSCs and their effects on osteogenesis. After 4 weeks of co-culture, MSCs grown with macrophages, especially M1 macrophages, had enhanced bone mineralization compared to MSCs grown alone. The level of bone formation after 4 weeks of culture was closely associated with prostaglandin E2 (PGE2) secretion early in osteogenesis. Treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective inhibitor, significantly reduced bone mineralization in all co-cultures but most dramatically in the M1-MSC co-culture. We also found that the presence of macrophages reduced the secretion of osteoprotegerin (OPG), the decoy RANKL receptor, suggesting that macrophages may indirectly modulate osteoclast activity in addition to enhancing bone formation. Taken together, these findings suggest that an initial pro-inflammatory phase modulated by M1 macrophages promotes osteogenesis in MSCs via the COX-2-PGE2 pathway. Understanding the complex interactions between macrophages and MSCs provide opportunities to optimize bone healing and other regenerative processes via modulation of the inflammatory response. This study provides one possible biological mechanism for the adverse effects of non-steroidal anti-inflammatory drugs on fracture healing and bone regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  View details for DOI 10.1002/jor.23553

  View details for PubMedID 28248001

• The Direct Anterior Approach is Associated With Early Revision Total Hip Arthroplasty. journal of arthroplasty Eto, S., Hwang, K., Huddleston, J. I., Amanatullah, D. F., Maloney, W. J., Goodman, S. B. 2017; 32 (3): 1001-1005

  Abstract

  The direct anterior approach for total hip arthroplasty (THA) has generated increased interest recently. The purpose of this study was to compare the duration to failure and reasons for revision of primary THA performed elsewhere and subsequently revised at our institution after the direct anterior vs other nonanterior surgical approaches to the hip.All primary THAs performed elsewhere and referred to our institution for revision were divided into the direct anterior approach (30 cases) or nonanterior approach groups (100 cases, randomly selected from 453 cases) based on the original surgical approach. Because all primary direct anterior THAs were originally performed after 2004 to eliminate temporal bias, we identified a subset of the nonanterior group in which the primary THA was performed after 2004 (known as the recent nonanterior group, 100 cases, randomly selected from 169 available cases).The mean duration from primary to revision THA was 3.0 ± 2.7 years (direct anterior approach), 12.0 ± 8.8 years (nonanterior approach), and 3.6 ± 2.8 years (recent nonanterior), respectively. There was a significant difference in time to revision between the direct anterior and nonanterior approach groups (P < .001). Aseptic loosening of the stem was significantly more frequent with the direct anterior approach group (9/30, 30.0%) when compared with the nonanterior group (8/100, 8.0%, P = .007) and the recent nonanterior group (7/100, 7.0%, P = .002).Revision of the femoral component for aseptic loosening is more commonly associated with the direct anterior approach in our referral practice.

  View details for DOI 10.1016/j.arth.2016.09.012

  View details for PubMedID 27843039

• Weight Gain After Primary Total Knee Arthroplasty Is Associated With Accelerated Time to Revision for Aseptic Loosening. journal of arthroplasty Lim, C. T., Goodman, S. B., Huddleston, J. I., Harris, A. H., Bhowmick, S., Maloney, W. J., Amanatullah, D. F. 2017

  Abstract

  Obesity is a major health problem worldwide and is associated with complications after total knee arthroplasty (TKA). It remains unknown whether a change in body mass index (BMI) after primary TKA affects the reasons for revision TKA or the time to revision TKA.A total of 160 primary TKAs referred to an academic tertiary center for revision TKA were retrospectively stratified according to change in BMI from the time of their primary TKA to revision TKA. The association between change in BMI and time to revision was also analyzed according to indication for revision of TKA using Pearson's chi-square test.The mean change in BMI from primary to revision TKA was 0.82 ± 3.5 kg/m(2). Maintaining a stable weight after primary TKA was protective against late revision TKA for any reason (P = .004). Patients who failed to reduce their BMI were revised for aseptic loosening earlier, at less than 5 years (P = .020), whereas those who reduced their BMI were revised later, at over 10 years (P = .004).Maintaining weight after primary TKA is protective against later revision TKA for any reason but failure to reduce weight after primary TKA is a risk factor for early revision TKA for aseptic loosening and osteolysis. Orthopedic surgeons should recommend against weight gain after primary TKA to reduce the risk of an earlier revision TKA in the event that a revision TKA is indicated.

  View details for DOI 10.1016/j.arth.2017.02.026

  View details for PubMedID 28318864

• Correlations between macrophage polarizing cytokines, inflammatory mediators, osteoclast activity, and toll-like receptors in tissues around aseptically loosened hip implants JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Jamsen, E., Kouri, V., Ainola, M., Goodman, S. B., Nordstrom, D. C., Eklund, K. K., Pajarinen, J. 2017; 105 (2): 454-463

  Abstract

  Aseptic loosening and osteolysis of joint replacements are driven by macrophage-mediated inflammatory reactions to implant-derived wear debris, but many aspects of these events remain poorly characterized. To better understand the relationships among inflammatory and chemotactic mediators, macrophage phenotype and polarizing cytokines, osteoclast activity, and Toll-like receptors (TLRs) in the pathogenesis of aseptic loosening, we determined how the relative expressions of these factors in the peri-implant tissues correlate to each other and to the life span of the implants using Pearson correlation. The expression of pro-inflammatory mediators and chemokines showed positive correlations among themselves, and with TLR4. Furthermore, M1-polarizing IFN-γ showed positive correlations with a number of pro-inflammatory and chemotactic mediators, whereas M2-polarizing IL-4 showed no such association. IL-8 expression significantly correlated with early time to revision. Similar trends were observed for TNF-α, IFN-γ and CCL3, while the opposite was detected for IL-4. However, none of the inflammatory mediators correlated with the markers of osteoclast activity or the RANKL/OPG ratio. The results highlight the importance of the inflammatory mediators, IFN-γ and TLR4 in the pathogenesis of aseptic loosening; increased pro-inflammatory status was associated with early time to revision, whereas IL-4 correlated with longer implant survival. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35913

  View details for Web of Science ID 000392506300011

• Editorial Comment: 2016 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2017; 475 (2): 334–35

  View details for PubMedID 27620803

• Response to Letter to the Editor on 'Tibiofemoral Dislocation After Total Knee Arthroplasty' JOURNAL OF ARTHROPLASTY Jethanandani, R. G., Maloney, W. J., Huddleston, J. I., Goodman, S. B., Amanatullah, D. F. 2017; 32 (2): 700-700

  View details for DOI 10.1016/j.arth.2016.10.021

  View details for PubMedID 27865569

• Mutant CCL2 protein coating mitigates wear particle-induced bone loss in a murine continuous polyethylene infusion model BIOMATERIALS Nabeshima, A., Pajarinen, J., Lin, T., Jiang, X., Gibon, E., Cordova, L. A., Loi, F., Lu, L., Jamsen, E., Egashira, K., Yang, F., Yao, Z., Goodman, S. B. 2017; 117: 1-9

  Abstract

  Wear particle-induced osteolysis limits the long-term survivorship of total joint replacement (TJR). Monocyte/macrophages are the key cells of this adverse reaction. Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is the most important chemokine regulating trafficking of monocyte/macrophages in particle-induced inflammation. 7ND recombinant protein is a mutant of CCL2 that inhibits CCL2 signaling. We have recently developed a layer-by-layer (LBL) coating platform on implant surfaces that can release biologically active 7ND. In this study, we investigated the effect of 7ND on wear particle-induced bone loss using the murine continuous polyethylene (PE) particle infusion model with 7ND coating of a titanium rod as a local drug delivery device. PE particles were infused into hollow titanium rods with or without 7ND coating implanted in the distal femur for 4 weeks. Specific groups were also injected with RAW 264.7 as the reporter macrophages. Wear particle-induced bone loss and the effects of 7ND were evaluated by microCT, immunohistochemical staining, and bioluminescence imaging. Local delivery of 7ND using the LBL coating decreased systemic macrophage recruitment, the number of osteoclasts and wear particle-induced bone loss. The development of a novel orthopaedic implant coating with anti-CCL2 protein may be a promising strategy to mitigate peri-prosthetic osteolysis.

  View details for DOI 10.1016/j.biomaterials.2016.11.039

  View details for PubMedID 27918885

• Decreased osteogenesis in mesenchymal stem cells derived from the aged mouse is associated with enhanced NF-?B activity. Journal of orthopaedic research Lin, T., Gibon, E., Loi, F., Pajarinen, J., Córdova, L. A., Nabeshima, A., Lu, L., Yao, Z., Goodman, S. B. 2017; 35 (2): 281-288

  Abstract

  Aging is associated with significant bone loss and delayed fracture healing. NF-κB activation is highly correlated with inflammatory-associated bone diseases including infection, wear particle exposure, and chronic inflammation during natural aging processes. The critical roles of NF-κB in both the pro-inflammatory response and osteoclast-mediated bone resorption have been well defined. However, the biological effects of NF-κB activation in mesenchymal stem cell (MSC)-mediated bone formation remain largely unknown. In the current study, bone marrow-MSCs were isolated from young (8 weeks old) and aged (72 weeks old) mice. NF-κB activity in MSCs at basal levels and under different biological conditions were determined by our recently established lentiviral vector-based luciferase reporter assay. We found that NF-κB activity was increased in aged MSCs at basal levels or when exposed to low dose (10 or 100 ng/ml) lipopolysaccharide (LPS); this effect was not seen when the cells were exposed to higher dose (1 μg/ml) LPS. During osteogenesis, NF-κB activity was increased in aged MSCs at weeks 1 and 2, but showed no significant difference at week 3. Both Smurf2 and TAZ, the NF-κB target genes that regulate osteogenic differentiation, were increased in aged MSCs. In addition, the expression of RANKL was dramatically increased, and OPG was decreased in aged MSCs. Our findings suggest that targeting NF-κB activity in MSCs has the potential to modulate aging-associated bone loss, or enhance bone-healing in aged patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:281-288, 2017.

  View details for DOI 10.1002/jor.23270

  View details for PubMedID 27105133

• NF-?B as a Therapeutic Target in Inflammatory-Associated Bone Diseases. Advances in protein chemistry and structural biology Lin, T., Pajarinen, J., Lu, L., Nabeshima, A., Cordova, L. A., Yao, Z., Goodman, S. B. 2017; 107: 117-154

  Abstract

  Inflammation is a defensive mechanism for pathogen clearance and maintaining tissue homeostasis. In the skeletal system, inflammation is closely associated with many bone disorders including fractures, nonunions, periprosthetic osteolysis (bone loss around orthopedic implants), and osteoporosis. Acute inflammation is a critical step for proper bone-healing and bone-remodeling processes. On the other hand, chronic inflammation with excessive proinflammatory cytokines disrupts the balance of skeletal homeostasis involving osteoblastic (bone formation) and osteoclastic (bone resorption) activities. NF-κB is a transcriptional factor that regulates the inflammatory response and bone-remodeling processes in both bone-forming and bone-resorption cells. In vitro and in vivo evidences suggest that NF-κB is an important potential therapeutic target for inflammation-associated bone disorders by modulating inflammation and bone-remodeling process simultaneously. The challenges of NF-κB-targeting therapy in bone disorders include: (1) the complexity of canonical and noncanonical NF-κB pathways; (2) the fundamental roles of NF-κB-mediated signaling for bone regeneration at earlier phases of tissue damage and acute inflammation; and (3) the potential toxic effects on nontargeted cells such as lymphocytes. Recent developments of novel inhibitors with differential approaches to modulate NF-κB activity, and the controlled release (local) or bone-targeting drug delivery (systemic) strategies, have largely increased the translational application of NF-κB therapy in bone disorders. Taken together, temporal modulation of NF-κB pathways with the combination of recent advanced bone-targeting drug delivery techniques is a highly translational strategy to reestablish homeostasis in the skeletal system.

  View details for DOI 10.1016/bs.apcsb.2016.11.002

  View details for PubMedID 28215222

• Smoking is associated with earlier time to revision of total knee arthroplasty. The Knee Lim, C. T., Goodman, S. B., Huddleston, J. I., Harris, A. H., Bhowmick, S. n., Maloney, W. J., Amanatullah, D. F. 2017

  Abstract

  Smoking is associated with early postoperative complications, increased length of hospital stay, and an increased risk of revision after total knee arthroplasty (TKA). However, the effect of smoking on time to revision TKA is unknown.A total of 619 primary TKAs referred to an academic tertiary center for revision TKA were retrospectively stratified according to the patient smoking status. Smoking status was then analyzed for associations with time to revision TKA using a Chi square test. The association was also analyzed according to the indication for revision TKA.Smokers (37/41, 90%) have an increased risk of earlier revision for any reason compared to non-smokers (274/357, 77%, p=0.031). Smokers (37/41, 90%) have an increased risk of earlier revision for any reason compared to ex-smokers (168/221, 76%, p=0.028). Subgroup analysis did not reveal a difference in indication for revision TKA (p>0.05).Smokers are at increased risk of earlier revision TKA when compared to non-smokers and ex-smokers. The risk for ex-smokers was similar to that of non-smokers. Smoking appears to have an all-or-none effect on earlier revision TKA as patients who smoked more did not have higher risk of early revision TKA. These results highlight the need for clinicians to urge patients not to begin smoking and encourage smokers to quit smoking prior to primary TKA.

  View details for PubMedID 28797880

• Reconstruction of Disrupted Extensor Mechanism After Total Knee Arthroplasty. The Journal of arthroplasty Lim, C. T., Amanatullah, D. F., Huddleston, J. I., Harris, A. H., Hwang, K. L., Maloney, W. J., Goodman, S. B. 2017

  Abstract

  Disruption of the extensor mechanism after total knee arthroplasty (TKA) is a debilitating complication that results in extension lag, limited range of motion, difficulty in walking, frequent falls, and chronic pain. This study presents the clinical and radiographic results of reconstruction after extensor mechanism disruption in TKA patients.Consecutive patients with allograft reconstruction of extensor mechanism after TKA were identified retrospectively from an academic tertiary center for revision TKA.Sixteen patients with a mean age of 61 ± 14 years at extensor mechanism reconstruction with a minimum of 2-year follow-up were included. The mean follow-up was 3.3 ± 2.2 years. Knee Society score (KSS), before and at final follow-up extension lag, range of motion, and radiographic change in patellar height were reviewed. There were statistically significant improvements between preoperative and final follow-up KSS (P < .001; KSS for pain, preoperative 40 ± 14 points to final follow-up 67 ± 15 points [P < .001]; KSS for function, preoperative 26 ± 21 points to final follow-up 48 ± 25 points [P < .001]). The extension lag was also reduced from 35° ± 16° preoperatively to 14° ± 18° (P < .001) at final follow-up. There was an average proximal patellar migration of 8 ± 10 mm. Five (31%) cases had an extensor lag of >30° or revision surgery for repeat extensor mechanism reconstruction, infection, or arthrodesis.Our 10-year experience using allografts during extensor mechanism reconstruction demonstrates reasonable outcomes, but failures are to be anticipated in approximately one-third of patients.

  View details for PubMedID 28634096

• Femoral Nerve Catheters Improve Home Disposition and Pain in Hip Fracture Patients Treated With Total Hip Arthroplasty. The Journal of arthroplasty Arsoy, D. n., Huddleston, J. I., Amanatullah, D. F., Giori, N. J., Maloney, W. J., Goodman, S. B. 2017

  Abstract

  Opioids have been the mainstay of treatment in the physiologically young geriatric hip fracture patient undergoing total hip arthroplasty (THA). However opioid-related side effects increase morbidity. Regional anesthesia may provide better analgesia, while decreasing opioid-related side effects. The goal of this study was to examine the effect of perioperative continuous femoral nerve blockade with regards to pain scores, opioid-related side effects and posthospital disposition in hip fracture patients undergoing THA.Twenty-nine consecutive geriatric hip fracture patients (22 women/7 men) underwent THA. Average follow-up was 8.3 months (6 weeks-39 months). Fifteen patients were treated with standard analgesia (SA). Fourteen patients received an ultrasound-guided insertion of a femoral nerve catheter after radiographic confirmation of a hip fracture. All complications and readmissions that occurred within 6 weeks of surgery were noted.Continuous femoral nerve catheter (CFNC) patients were discharged home more frequently than SA patients (43% for CFNC vs 7% for SA; P = .023). CFNC patients reported lower average pain scores preoperatively (P < .0001), on postoperative day 1 (P = .005) and postoperative day 2 (P = .037). Preoperatively, CFNC patients required 61% less morphine equivalent (P = .007). CFNC patients had a lower rate of opioid-related side effects compared with SA patients (7% vs 47%; P = .035).CFNC patients were discharged to home more frequently. Use of a CFNC decreased daily average patient-reported pain scores, preoperative opioid usage, and opioid-related side effects after THA for hip fracture. Based on these data, we recommend routine use of perioperative CFNC in hip fracture patients undergoing THA.

  View details for PubMedID 28641968

• Implants for Joint Replacement of the Hip and Knee MATERIALS AND DEVICES FOR BONE DISORDERS Gallo, J., Gibon, E., Goodman, S. B., Bose, S., Bandyopadhyay, A. 2017: 119–96

  View details for Web of Science ID 000413677700005

• Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial. JAMA surgery Hah, J. n., Mackey, S. C., Schmidt, P. n., McCue, R. n., Humphreys, K. n., Trafton, J. n., Efron, B. n., Clay, D. n., Sharifzadeh, Y. n., Ruchelli, G. n., Goodman, S. n., Huddleston, J. n., Maloney, W. J., Dirbas, F. M., Shrager, J. n., Costouros, J. n., Curtin, C. n., Carroll, I. n. 2017

  Abstract

  Guidelines recommend using gabapentin to decrease postoperative pain and opioid use, but significant variation exists in clinical practice.To determine the effect of perioperative gabapentin on remote postoperative time to pain resolution and opioid cessation.A randomized, double-blind, placebo-controlled trial of perioperative gabapentin was conducted at a single-center, tertiary referral teaching hospital. A total of 1805 patients aged 18 to 75 years scheduled for surgery (thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, and shoulder arthroscopy) were screened. Participants were enrolled from May 25, 2010, to July 25, 2014, and followed up for 2 years postoperatively. Intention-to-treat analysis was used in evaluation of the findings.Gabapentin, 1200 mg, preoperatively and 600 mg, 3 times a day postoperatively or active placebo (lorazepam, 0.5 mg) preoperatively followed by inactive placebo postoperatively for 72 hours.Primary outcome was time to pain resolution (5 consecutive reports of 0 of 10 possible levels of average pain at the surgical site on the numeric rating scale of pain). Secondary outcomes were time to opioid cessation (5 consecutive reports of no opioid use) and the proportion of participants with continued pain or opioid use at 6 months and 1 year.Of 1805 patients screened for enrollment, 1383 were excluded, including 926 who did not meet inclusion criteria and 273 who declined to participate. Overall, 8% of patients randomized were lost to follow-up. A total of 202 patients were randomized to active placebo and 208 patients were randomized to gabapentin in the intention-to-treat analysis (mean [SD] age, 56.7 [11.7] years; 256 (62.4%) women and 154 (37.6%) men). Baseline characteristics of the groups were similar. Perioperative gabapentin did not affect time to pain cessation (hazard ratio [HR], 1.04; 95% CI, 0.82-1.33; P = .73) in the intention-to-treat analysis. However, participants receiving gabapentin had a 24% increase in the rate of opioid cessation after surgery (HR, 1.24; 95% CI, 1.00-1.54; P = .05). No significant differences were noted in the number of adverse events as well as the rate of medication discontinuation due to sedation or dizziness (placebo, 42 of 202 [20.8%]; gabapentin, 52 of 208 [25.0%]).Perioperative administration of gabapentin had no effect on postoperative pain resolution, but it had a modest effect on promoting opioid cessation after surgery. The routine use of perioperative gabapentin may be warranted to promote opioid cessation and prevent chronic opioid use. Optimal dosing and timing of perioperative gabapentin in the context of specific operations to decrease opioid use should be addressed in further research.clinicaltrials.gov Identifier: NCT01067144.

  View details for PubMedID 29238824

• 100% Clean and renewable wind, water, and sunlight all-sector energy roadmaps for 139 countries of the world JOULE Jacobson, M. Z., Delucchi, M. A., Bauer, Z. A., Goodman, S. C., Chapman, W. E., Cameron, M. A., et al 2017; 1 (1): 108-121

  View details for DOI 10.1016/j.joule.2017.07.005

• Murine Model of Progressive Orthopaedic Wear Particle Induced Chronic Inflammation and Osteolysis. Tissue engineering. Part C, Methods Pajarinen, J. n., Nabeshima, A. n., Lin, T. H., Sato, T. n., Gibon, E. n., Jämsen, E. n., Lu, L. n., Nathan, K. n., Yao, Z. n., Goodman, S. B. 2017

  Abstract

  Periprosthetic osteolysis and subsequent aseptic loosening of total joint replacements are driven by byproducts of wear released from the implant. Wear particles cause macrophage mediated inflammation that culminates with periprosthetic bone loss. Most current animal models of particle- induced osteolysis are based on the acute inflammatory reaction induced by wear debris, which is distinct from the slowly progressive clinical scenario. To address this limitation we previously developed a murine model of periprosthetic osteolysis that is based on slow continuous delivery of wear particles into the murine distal femur over a period of 4 weeks. The particle delivery was accomplished by using subcutaneously implanted osmotic pumps and tubing, and a hollow titanium rod press-fit into the distal femur. In this study we report a modification of our prior model in which particle delivery is extended to 8 weeks to better mimic the progressive development of periprosthetic osteolysis and to allow the assessment of interventions in a setting where the chronic particle induced osteolysis is already present at the initiation of the treatment. Compared to 4 week samples extending the particle delivery to 8 weeks significantly exacerbated the local bone loss observed with µCT and the amount of both peri-implant F4/80+ macrophages and TRAP+ osteoclasts detected with immunohistochemical and histochemical stainings. Furthermore systemic recruitment of reporter macrophages to peri-implant tissues observed with bioluminescence imaging continued even at the later stages of particle induced inflammation. This modified model system could provide new insights into the mechanisms of chronic inflammatory bone loss and be particularly useful in assessing the efficacy of treatments in a setting that resembles the clinical scenario of developing periprosthetic osteolysis more closely than currently existing model systems.

  View details for PubMedID 28978284

• CCL2, CCL5 and IGF-1 Participate in The Immunomodulation of Osteogenesis during M1/M2 Transition In Vitro. Journal of biomedical materials research. Part A Córdova, L. A., Loi, F. n., Lin, T. H., Gibon, E. n., Pajarinen, J. n., Nabeshima, A. n., Lu, L. n., Yao, Z. n., Goodman, S. B. 2017

  Abstract

  The modulation of macrophage phenotype from pro-inflammatory (M1) to tissue healing (M2) via exogenous addition of interleukin-4 (IL-4) facilitates osteogenesis; however, the molecular mediators underlying this phenomenon remain unknown. This study characterizes the IL-4-dependent paracrine crosstalk between macrophages and osteoprogenitors and its effect on osteogenesis in vitro. Primary murine M1 were co-cultured with MC3T3 cells (M1-MC3T3) in both transwell plates and direct co-cultures. To modulate M1 to M2, M1-MC3T3 were treated with IL-4 (20ng/mL) at day 3 after seeding (M1+IL-4-MC3T3). Selected molecular targets were assessed at days 3 and 6 after seeding at protein and mRNA levels. Mineralization was assessed at day 21. Transwell M1+IL-4-MC3T3 significantly enhanced the secretion of CCL2/MCP-1, IGF-1 and to a lesser degree, CCL5/RANTES at day 6. At day 3, alkaline phosphatase (Alpl) was up-regulated in direct M1-MC3T3. At day 6, Smurf2 and Insulin growth factor-1 (Igf-1) were down-regulated and up-regulated respectively in direct M1+IL-4-MC3T3. Finally, M1+IL-4-MC3T3 increased bone matrix mineralization compared with MC3T3 cells in transwell, but this was significantly less than M1-MC3T3. Taken together, macrophage subtypes enhanced the osteogenesis in transwell setting and the transition from M1 to M2 was associated with an increase in bone anabolic factors CCL2/MCP-1, CCL5/RANTES and IGF-1 in vitro. This article is protected by copyright. All rights reserved.

  View details for PubMedID 28782174

• Orthopaedic Wear Particle-induced Bone Loss and Exogenous Macrophage Infiltration is mitigated by Local Infusion of NF-κB Decoy Oligodeoxynucleotide. Journal of biomedical materials research. Part A Lin, T. n., Pajarinen, J. n., Nabeshima, A. n., Córdova, L. A., Loi, F. n., Gibon, E. n., Lu, L. n., Nathan, K. n., Jämsen, E. n., Yao, Z. n., Goodman, S. B. 2017

  Abstract

  Excessive production of wear particles from total joint replacements (TJRs) induces chronic inflammation, macrophage infiltration, and consequent bone loss (periprosthetic osteolysis). This inflammation and bone remodeling are critically regulated by the transcription factor NF-κB. We previously demonstrated that inhibition of NF-κB signaling by using the decoy oligodeoxynucleotide (ODN) mitigates polyethylene wear particle-induced bone loss using in vitro and in vivo models. However, the mechanisms of NF-κB decoy ODN action, and in particular its impact on systemic macrophage recruitment, remain unknown. In the current study, this systemic macrophage infiltration was examined in our established murine femoral continuous particle infusion model. RAW264.7 murine macrophages expressing a luciferase reporter gene were injected into the systemic circulation. Quantification of bioluminescence showed that NF-κB decoy ODN reduced the homing of these reporter macrophages into the distal femurs exposed to continuous particle delivery. Particle-induced reduction in bone mineral density at the distal diaphysis of the femur was also mitigated by infusion of decoy ODN. Histological staining showed that the decoy ODN infusion decreased osteoclast and macrophage numbers, but had no significant effects on osteoblasts. Local infusion of NF-κB decoy ODN reduced systemic macrophage infiltration and mitigated particle-induced bone loss, thus providing a potential strategy to treat periprosthetic osteolysis. This article is protected by copyright. All rights reserved.

  View details for PubMedID 28782280

• Establishment of NF-κB sensing and interleukin-4 secreting mesenchymal stromal cells as an "on-demand" drug delivery system to modulate inflammation. Cytotherapy Lin, T. n., Pajarinen, J. n., Nabeshima, A. n., Lu, L. n., Nathan, K. n., Yao, Z. n., Goodman, S. B. 2017

  Abstract

  Chronic inflammation is associated with up-regulation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and excessive inflammatory cytokine secretion by M1 macrophages. The anti-inflammatory cytokine interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory and tissue-regenerative M2 phenotype, thus reducing inflammation and enhancing tissue regeneration. We have generated NF-κB responsive, or constitutively active IL-4 expression lentiviral vectors transduced into murine bone marrow-derived mesenchymal stromal cells (MSCs). MSCs with a constitutively active IL-4 expression vector produced large quantities of IL-4 continuously, whereas IL-4 secretion was significantly induced by lipopolysaccharide (LPS) in the NF-κB sensing MSCs. In contrast, LPS had no effect on MSCs with IL-4 secretion driven by a constitutively active promoter. We also found that intermittent and continuous LPS treatment displayed distinct NF-κB activation profiles, and this regulation was independent of IL-4 signaling. The supernatant containing IL-4 from the LPS-treated MSCs suppressed M1 marker (inducible nitric oxide synthase [iNOS] and tumor necrosis factor alpha [TNFα]) expression and enhanced M2 marker (Arginase 1, CD206 and IL1 receptor antagonist [IL1Ra]) expression in primary murine macrophages. The IL-4 secretion at the basal, non-LPS induced level was sufficient to suppress TNFα and enhance Arginase 1 at a lower level, but had no significant effects on iNOS, CD206 and IL1Ra expression. Finally, IL-4 secretion at basal or LPS-induced levels significantly suppressed osteogenic differentiation of MSCs. Our findings suggest that the IL-4 secreting MSCs driven by NF-κB sensing or constitutive active promoter have great potential for mitigating the effects of chronic inflammation and promoting earlier tissue regeneration.

  View details for PubMedID 28739167

• Elevated Body Mass Index Is Associated With Early Total Knee Revision for Infection JOURNAL OF ARTHROPLASTY Electricwala, A. J., Jethanandani, R. G., Narkbunnam, R., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2017; 32 (1): 252-255

  Abstract

  Obesity affects over half a billion people worldwide, including one-third of men and women in the United States. Obesity is associated with higher postoperative complication rates after total knee arthroplasty (TKA). It remains unknown whether obese patients progress to revision TKA faster than nonobese patients.A total of 666 consecutive primary TKAs referred to an academic tertiary care center for revision TKA were retrospectively stratified according to body mass index (BMI), reason for revision TKA, and time from primary to revision TKA.When examining primary TKAs referred for revision TKA, increasing BMI adversely affected the mean time to revision TKA. The percent of referred TKAs revised by 5 years was 54% for a normal BMI, 64% for an overweight patient, 71% for an obese class I patient, 68% for an obese class II patient, and 73% for a morbidly obese patient. There was a significant difference in time to revision TKA between patients with normal BMI and elevated BMI (P = .005). There was a significant increase in early revision TKA for infection in patients with an elevated BMI (54%, 74/138) when compared with the normal BMI patients (24%, 8/33, P < .003, relative risk ratio = 2.3, absolute risk = 30%, number needed to treat = 3.3). There was no significant increase in acute, early, midterm, or late revision TKA for aseptic loosening and/or osteolysis, instability, stiffness, or other causes between patients with normal BMI and elevated BMI.An elevated BMI is a risk factor for early referral to a tertiary care center for revision TKA. Specifically, orthopedic surgeons should convey to overweight and obese patients that they have at least a 130% increased relative risk and a 30% absolute risk of revision TKA for an early infection if referred for revision TKA. Patient expectations and counseling as well as reimbursement should account for the greater risks when performing a TKA on patients with an elevated BMI.

  View details for DOI 10.1016/j.arth.2016.05.071

  View details for PubMedID 27421585

• Cortical Strut Allograft Support of Modular Femoral Junctions During Revision Total Hip Arthroplasty. journal of arthroplasty Lim, C. T., Amanatullah, D. F., Huddleston, J. I., Hwang, K. L., Maloney, W. J., Goodman, S. B. 2016

  Abstract

  There is risk of junction failure when using modular femoral stems for revision total hip arthroplasty (THA), especially with loss of bone stock in the proximal femur. Using a cortical strut allograft may provide additional support of a modular femoral construct in revision THA.We reviewed prospectively gathered clinical and radiographic data for 28 revision THAs performed from 2004 to 2014 using cementless modular femoral components with cortical strut allograft applied to supplement proximal femoral bone loss: 5 (18%) were fluted taper designs and 23 (82%) were porous cylindrical designs All the patients had a Paprosky grade IIIA or greater femoral defect. The mean follow-up was 5.4 ± 3.9 years.The Harris Hip Scores improved from 26 ± 10 points preoperatively to 71 ± 10 points at final follow-up (P < .001). The Western Ontario McMaster Universities Osteoarthritis Index scores improved from 45 ± 12 points preoperatively to 76 ± 12 points at final follow-up (P < .001). Eighty-nine percent (25 hips) of all revision or conversion THAs were in place at final follow-up. Three (11%) patients underwent reoperations, 2 for infection and 1 for periprosthetic fracture. There was no statistical significant change in femoral component alignment (P = .161) at final follow-up. Mean subsidence was 1.8 ± 1.3 mm at final follow-up. Femoral diameter increased from initial postoperative imaging to final follow-up imaging by a mean of 9.1 ± 5.1 mm (P < .001) and cortical width increased by a mean of 4.5 ± 2.2 mm (P < .001). Twenty-seven hips (96%) achieved union between the cortical strut allograft and the host femur.The use of a modular femoral stem in a compromised femur with a supplementary cortical strut allgraft is safe and provides satisfactory clinical and radiological outcomes.

  View details for DOI 10.1016/j.arth.2016.12.011

  View details for PubMedID 28130016

• Use of Cortical Strut Allograft After Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty. journal of arthroplasty Lim, C. T., Amanatullah, D. F., Huddleston, J. I., Hwang, K. L., Maloney, W. J., Goodman, S. B. 2016

  Abstract

  Cortical strut allografts restore bone stock and improve postoperative clinical scores after revision total hip arthroplasty (THA). However, use of a cortical strut allograft is implicated in delayed healing of an extended trochanteric osteotomy (ETO). To date, there are no reports directly comparing ETO with or without cortical strut allografts.We reviewed prospectively gathered data on 50 revision THAs performed from 2004-2014 using an ETO. We compared the demographic, radiological, and clinical outcome of patients with (16 hips) and without (34 hips) cortical strut allograft after an ETO.There were no significant differences in Western Ontario McMaster Universities Osteoarthritis Index or Harris Hip Score between the ETOs with and without a cortical strut allograft. Fifteen of the ETOs (94%) with a cortical strut allograft and 31 of the ETOs (91%) without a cortical strut allograft were in situ at final follow-up (P = 1.000). A higher proportion hips with cortical strut allograft (100%, 16 patients) had preoperative Paprosky grade bone loss more than IIIA compared to those without allograft (29%, 10 patients) (P < .001). There were no differences in femoral stem subsidence (P = .207), alignment (P = .934), or migration of the osteotomized fragment (P = .171). Fourteen of the ETOs (88%) in patients with cortical strut allograft united compared to 34 ETOs (100%) in patients without allograft (P = .095).Our study shows that the use of cortical strut allograft during revision THA with ETO does not reduce the rate of union, radiological or clinical outcomes.

  View details for DOI 10.1016/j.arth.2016.12.002

  View details for PubMedID 28110850

• CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis. Annals of the rheumatic diseases Raghu, H., Lepus, C. M., Wang, Q., Wong, H. H., Lingampalli, N., Oliviero, F., Punzi, L., Giori, N. J., Goodman, S. B., Chu, C. R., Sokolove, J. B., Robinson, W. H. 2016

  Abstract

  While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/CCR5 chemokine axes in OA pathogenesis.Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA. The pharmacological utility of blocking CCL2/CCR2 signalling in mouse OA was investigated using bindarit, a CCL2 synthesis inhibitor, and RS-504393, a CCR2 antagonist. Levels of monocyte chemoattractants in synovial tissues and fluids from patients with joint injuries without OA and those with established OA were investigated using a combination of microarray analyses, multiplexed cytokine assays and immunostains.Mice lacking CCL2 or CCR2, but not CCL5 or CCR5, were protected against OA with a concomitant reduction in local monocyte/macrophage numbers in their joints. In synovial fluids from patients with OA, levels of CCR2 ligands (CCL2, CCL7 and CCL8) but not CCR5 ligands (CCL3, CCL4 and CCL5) were elevated. We found that CCR2+ cells are abundant in human OA synovium and that CCR2+ macrophages line, invade and are associated with the erosion of OA cartilage. Further, blockade of CCL2/CCR2 signalling markedly attenuated macrophage accumulation, synovitis and cartilage damage in mouse OA.Our findings demonstrate that monocytes recruited via CCL2/CCR2, rather than by CCL5/CCR5, propagate inflammation and tissue damage in OA. Selective targeting of the CCL2/CCR2 system represents a promising therapeutic approach for OA.

  View details for DOI 10.1136/annrheumdis-2016-210426

  View details for PubMedID 27965260

• Revision Hip Arthroplasty Using a Modular, Cementless Femoral Stem: Intermediate-Term Follow-Up. journal of arthroplasty Sivananthan, S., Lim, C., Narkbunnam, R., Sox-Harris, A., Huddleston, J. I., Goodman, S. B. 2016

  Abstract

  Modular femoral stem provides flexibility in femoral reconstruction, ensuring improved "fit and fill". However, there are risks of junction failure and corrosion, as well as cost concerns in the use of modular femoral stems.We reviewed prospectively-gathered clinical and radiographic data on revision total hip arthroplasties (THAs) performed from 2001-2007 using modular, cementless femoral component performed by the 2 senior authors. Patients with a minimum follow-up of 7 years were included in this study.Sixty-four patients (68 hips) with a median age of 68 ± 14 years (range 40-92 years) at revision THA were included. The median follow-up was 11.0 ± 1.8 years (range 7-14). Harris hip score, femoral stem subsidence, and stem osseointegration were recorded. The Harris hip score improved from an average of 38.1-80.1 (P < .01). Five hips had one or more dislocations. Seven patients underwent reoperations, 3 of which did not involve the stem. Four stems required revision because of infection, recurrent dislocation, or suboptimal implant position. Survival rates for any reasons and revision for femoral stems were 90% and 94%, respectively, at the most recent follow-up. Four stems subsided more than 5 mm, but established stable osseointegration thereafter. Seven nonloose stems (10.2%) demonstrated radiolucent lines in Gruen zones 1 and 7. No complications regarding the modular junction were encountered.Modular, cementless, extensively porous-coated femoral components have demonstrated intermediate-term clinical and radiographic success. Initial distal intramedullary fixation ensures stability, and proximal modularity further maximizes fit and fill.

  View details for DOI 10.1016/j.arth.2016.10.033

  View details for PubMedID 27923596

• Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nature nanotechnology Zanganeh, S., Hutter, G., Spitler, R., Lenkov, O., Mahmoudi, M., Shaw, A., Pajarinen, J. S., Nejadnik, H., Goodman, S., Moseley, M., Coussens, L. M., Daldrup-Link, H. E. 2016; 11 (11): 986-994

  Abstract

  Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

  View details for DOI 10.1038/nnano.2016.168

  View details for PubMedID 27668795

• Deficient Activity of the Nuclease MRE11A Induces T Cell Aging and Promotes Arthritogenic Effector Functions in Patients with Rheumatoid Arthritis. Immunity Li, Y., Shen, Y., Hohensinner, P., Ju, J., Wen, Z., Goodman, S. B., Zhang, H., Goronzy, J. J., Weyand, C. M. 2016; 45 (4): 903-916

  Abstract

  Immune aging manifests with a combination of failing adaptive immunity and insufficiently restrained inflammation. In patients with rheumatoid arthritis (RA), T cell aging occurs prematurely, but the mechanisms involved and their contribution to tissue-destructive inflammation remain unclear. We found that RA CD4(+) T cells showed signs of aging during their primary immune responses and differentiated into tissue-invasive, proinflammatory effector cells. RA T cells had low expression of the double-strand-break repair nuclease MRE11A, leading to telomeric damage, juxtacentromeric heterochromatin unraveling, and senescence marker upregulation. Inhibition of MRE11A activity in healthy T cells induced the aging phenotype, whereas MRE11A overexpression in RA T cells reversed it. In human-synovium chimeric mice, MRE11A(low) T cells were tissue-invasive and pro-arthritogenic, and MRE11A reconstitution mitigated synovitis. Our findings link premature T cell aging and tissue-invasiveness to telomere deprotection and heterochromatin unpacking, identifying MRE11A as a therapeutic target to combat immune aging and suppress dysregulated tissue inflammation.

  View details for DOI 10.1016/j.immuni.2016.09.013

  View details for PubMedID 27742546

• Tibiofemoral Dislocation After Total Knee Arthroplasty. journal of arthroplasty Jethanandani, R. G., Maloney, W. J., Huddleston, J. I., Goodman, S. B., Amanatullah, D. F. 2016; 31 (10): 2282-2285

  Abstract

  Tibiofemoral dislocation after total knee arthroplasty (TKA) is a rare complication. Published case reports describe fewer than 6 patients, making conclusions about the etiology, epidemiology, complications, and treatment of tibiofemoral dislocation difficult. This case series highlights common demographic features, potential causes, and difficulties during the management of tibiofemoral dislocations after TKA.Between 2005 and 2014, 14 patients presented to our institution with a tibiofemoral dislocation. Patients were excluded if they had patellofemoral dislocation or subluxation without a tibiofemoral dislocation. We retrospectively reviewed patient demographics, time to first dislocation, number of dislocations, time to surgical intervention, complications, and potential etiologies of tibiofemoral dislocation.Twelve of 14 patients were female. Their mean body mass index was 33 ± 10 kg/m(2). Thirteen of 14 patients had a mean of 2.0 ± 1.4 dislocations. Four patients dislocated due to polyethylene damage and 5 due to ligamentous incompetence. Twelve of 14 patients required open surgical intervention. Complications in this patient population were common with 3 cases of infection, 7 cases of multiple dislocation, 2 cases of popliteal artery laceration, 1 case receiving a fusion, and 1 case receiving an amputation.Patients with tibiofemoral dislocation after TKA are predominantly obese, female, and have a high risk for complications. They dislocate predominantly because of polyethylene damage or ligamentous incompetence. Re-dislocation is common if treated with closed reduction alone.

  View details for DOI 10.1016/j.arth.2016.03.010

  View details for PubMedID 27084503

• Correlations between macrophage polarizing cytokines, inflammatory mediators, osteoclast activity, and toll-like receptors in tissues around aseptically loosened hip implants. Journal of biomedical materials research. Part A Jämsen, E., Kouri, V., Ainola, M., Goodman, S. B., Nordström, D. C., Eklund, K. K., Pajarinen, J. 2016

  Abstract

  Aseptic loosening and osteolysis of joint replacements are driven by macrophage-mediated inflammatory reactions to implant-derived wear debris, but many aspects of these events remain poorly characterized. To better understand the relationships among inflammatory and chemotactic mediators, macrophage phenotype and polarizing cytokines, osteoclast activity, and Toll-like receptors (TLRs) in the pathogenesis of aseptic loosening, we determined how the relative expressions of these factors in the peri-implant tissues correlate to each other and to the life span of the implants using Pearson correlation. The expression of pro-inflammatory mediators and chemokines showed positive correlations among themselves, and with TLR4. Furthermore, M1-polarizing IFN-γ showed positive correlations with a number of pro-inflammatory and chemotactic mediators, whereas M2-polarizing IL-4 showed no such association. IL-8 expression significantly correlated with early time to revision. Similar trends were observed for TNF-α, IFN-γ and CCL3, while the opposite was detected for IL-4. However, none of the inflammatory mediators correlated with the markers of osteoclast activity or the RANKL/OPG ratio. The results highlight the importance of the inflammatory mediators, IFN-γ and TLR4 in the pathogenesis of aseptic loosening; increased pro-inflammatory status was associated with early time to revision, whereas IL-4 correlated with longer implant survival. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35913

  View details for PubMedID 27669374

• The effect of local IL-4 delivery or CCL2 blockade on implant fixation and bone structural properties in a mouse model of wear particle induced osteolysis. Journal of biomedical materials research. Part A Sato, T., Pajarinen, J., Behn, A., Jiang, X., Lin, T., Loi, F., Yao, Z., Egashira, K., Yang, F., Goodman, S. B. 2016; 104 (9): 2255-2262

  Abstract

  Modulation of macrophage polarization and prevention of CCL2-induced macrophage chemotaxis are emerging strategies to reduce wear particle induced osteolysis and aseptic total joint replacement loosening. In this study, the effect of continuous IL-4 delivery or bioactive implant coating that constitutively releases a protein inhibitor of CCL2 signaling (7ND) on particle induced osteolysis were studied in the murine continuous femoral intramedullary particle infusion model. Polyethylene particles with or without IL-4 were infused into mouse distal femurs implanted with hollow titanium rods using subcutaneous infusion pumps. In another experimental group, particles were infused into the femur through a 7ND coated rod. After four weeks, fixation of the implant was assessed using a pullout test. The volume of trabecular bone and the geometry of the local cortical bone were assessed by µCT and the corresponding structural properties of the cortical bone determined by torsional testing. Continuous IL-4 delivery led to increased trabecular bone volume as well as enhanced local bone geometry and structural properties, while 7ND implant coating did not have effect on these parameters. The results suggest that local IL-4 treatment is a promising strategy to mitigate wear particle induced osteolysis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35759

  View details for PubMedID 27114284

• Emperor's new clothes: Is particle disease really infected particle disease? JOURNAL OF ORTHOPAEDIC RESEARCH Wasko, M. K., Goodman, S. B. 2016; 34 (9): 1497–1504

  Abstract

  Aseptic loosening remains the most significant long-term complication of total hip replacement. The current paradigm points to an inflammatory response to wear particles as its main trigger. Recently, there have been increasing numbers of positive bacterial isolates reported among patients with clinically absent infection. This paper reviews existing evidence on possible involvement of bacteria and microbial-associated molecular patterns in the pathology of so-called "aseptic loosening." © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1497-1504, 2016.

  View details for PubMedID 27175824

• Obesity is Associated With Early Total Hip Revision for Aseptic Loosening JOURNAL OF ARTHROPLASTY Electricwala, A. J., Narkbunnam, R., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2016; 31 (9): S217-S220

  Abstract

  Obesity affects more than half a billion people worldwide, including one-third of men and women in the United States. Obesity is associated with higher postoperative complication rates after total hip arthroplasty (THA). It remains unknown whether obese patients progress to revision THA faster than nonobese patients.A total of 257 consecutive primary THAs referred to an academic tertiary care center for revision THA were retrospectively stratified according to preoperative body mass index (BMI), reason for revision THA, and time from primary to revision THA.When examining primary THAs referred for revision THA, increasing BMI adversely affected the mean time to revision THA. The percentage of primary THAs revised at 5 years was 25% for a BMI of 18-25, 38% for a BMI of 25-30, 56% for a BMI of 30-35, 73% for a BMI of 35-40, and 75% for a BMI of greater than 40 (P < .001). The percentage of primary THAs revised at 15 years was 70%, 82%, 87%, 94%, and 100%, respectively (P < .001). A significant increase in early revision THA for aseptic loosening/osteolysis in obese patients (56%, 23/41) when compared with the nonobese patients (12%, 10/83, P < .001, relative risk ratio = 4.7).Preoperative BMI influences the time of failure of primary THAs referred to an academic tertiary care for revision THA as well as the mechanism of failure. Specifically, obesity increased in the relative risk of early revision THA due to aseptic loosening/osteolysis by 4.7 fold.

  View details for DOI 10.1016/j.arth.2016.02.073

  View details for Web of Science ID 000382208900046

• The effect of SDF-1 on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Zwingenberger, S., Langanke, R., Vater, C., Lee, G., Niederlohmann, E., Sensenschmidt, M., Jacobi, A., Bernhardt, R., Muders, M., Rammelt, S., Knaack, S., Gelinsky, M., Guenther, K., Goodman, S. B., Stiehler, M. 2016; 104 (9): 2126-2134

  Abstract

  The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.

  View details for DOI 10.1002/jbm.a.35744

  View details for Web of Science ID 000380728900002

• Obesity is Associated With Early Total Hip Revision for Aseptic Loosening. journal of arthroplasty Electricwala, A. J., Narkbunnam, R., Huddleston, J. I., Maloney, W. J., Goodman, S. B., Amanatullah, D. F. 2016; 31 (9): 217-220

  Abstract

  Obesity affects more than half a billion people worldwide, including one-third of men and women in the United States. Obesity is associated with higher postoperative complication rates after total hip arthroplasty (THA). It remains unknown whether obese patients progress to revision THA faster than nonobese patients.A total of 257 consecutive primary THAs referred to an academic tertiary care center for revision THA were retrospectively stratified according to preoperative body mass index (BMI), reason for revision THA, and time from primary to revision THA.When examining primary THAs referred for revision THA, increasing BMI adversely affected the mean time to revision THA. The percentage of primary THAs revised at 5 years was 25% for a BMI of 18-25, 38% for a BMI of 25-30, 56% for a BMI of 30-35, 73% for a BMI of 35-40, and 75% for a BMI of greater than 40 (P < .001). The percentage of primary THAs revised at 15 years was 70%, 82%, 87%, 94%, and 100%, respectively (P < .001). A significant increase in early revision THA for aseptic loosening/osteolysis in obese patients (56%, 23/41) when compared with the nonobese patients (12%, 10/83, P < .001, relative risk ratio = 4.7).Preoperative BMI influences the time of failure of primary THAs referred to an academic tertiary care for revision THA as well as the mechanism of failure. Specifically, obesity increased in the relative risk of early revision THA due to aseptic loosening/osteolysis by 4.7 fold.

  View details for DOI 10.1016/j.arth.2016.02.073

  View details for PubMedID 27108056

• The effect of SDF-1a on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model. Journal of biomedical materials research. Part A Zwingenberger, S., Langanke, R., Vater, C., Lee, G., Niederlohmann, E., Sensenschmidt, M., Jacobi, A., Bernhardt, R., Muders, M., Rammelt, S., Knaack, S., Gelinsky, M., Günther, K., Goodman, S. B., Stiehler, M. 2016; 104 (9): 2126-2134

  Abstract

  The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.

  View details for DOI 10.1002/jbm.a.35744

  View details for PubMedID 27060915

• NF-?B decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model. Acta biomaterialia Lin, T., Pajarinen, J., Sato, T., Loi, F., Fan, C., Córdova, L. A., Nabeshima, A., Gibon, E., Zhang, R., Yao, Z., Goodman, S. B. 2016; 41: 273-281

  Abstract

  Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4 weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis.Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone-resorbing cells), and osteoblasts (bone-forming cells) could potentially mitigate this disease. Here we demonstrated that local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) mitigated ultra-high molecular weight polyethylene (UHMWPE) wear particleinduced bone loss in a clinically relevant murine model. The protective effects of decoy ODN was associated with reduced macrophage infiltration and osteoclast activation, but had no significant effects on osteoblast numbers. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced bone loss.

  View details for DOI 10.1016/j.actbio.2016.05.038

  View details for PubMedID 27260104

• Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up. Journal of hip preservation surgery Shapiro, L. M., Safran, M. R., Maloney, W. J., Goodman, S. B., Huddleston, J. I., Bellino, M. J., Scuderi, G. J., Abrams, G. D. 2016; 3 (3): 229-235

  Abstract

  Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin-aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson's correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy.

  View details for DOI 10.1093/jhps/hnw013

  View details for PubMedID 27583163

• Hip arthroplasty for treatment of advanced osteonecrosis: comprehensive review of implant options, outcomes and complications. Orthopedic research and reviews Waewsawangwong, W., Ruchiwit, P., Huddleston, J. I., Goodman, S. B. 2016; 8: 13-29

  Abstract

  Surgical treatment for late stage (post-collapse) osteonecrosis of the femoral head is controversial. In these situations, the outcome of joint preservation procedures is poor. There are several arthroplasty options for late-stage disease. The clinical outcomes of hemiarthroplasty and hemiresurfacing are unpredictable because of progressive acetabular cartilage degeneration. Total hip resurfacing may be associated with further vascular insult to the femoral head and early failure of the implant. Total hip replacement with metal-on-conventional polyethylene bearing surfaces has been the gold standard, but implant survivorship is limited in young active patients due to wear and osteolysis. Newer alternative bearing surfaces may have improved wear characteristics, but their durability must be confirmed in longer-term studies.

  View details for DOI 10.2147/ORR.S35547

  View details for PubMedID 30774467

  View details for PubMedCentralID PMC6209358

• The biological response to orthopaedic implants for joint replacement: Part I: Metals. Journal of biomedical materials research. Part B, Applied biomaterials Gibon, E., Amanatullah, D. F., Loi, F., Pajarinen, J., Nabeshima, A., Yao, Z., Hamadouche, M., Goodman, S. B. 2016

  Abstract

  Joint replacement is a commonly performed, highly successful orthopaedic procedure, for which surgeons have a large choice of different materials and implant designs. The materials used for joint replacement must be both biologically acceptable to minimize adverse local tissue reactions, and robust enough to support weight bearing during common activities of daily living. Modern joint replacements are made from metals and their alloys, polymers, ceramics, and composites. This review focuses on the biological response to the different biomaterials used for joint replacement. In general, modern materials for joint replacement are well tolerated by the body as long as they are in bulk (rather than in particulate or ionic) form, are mechanically stable and noninfected. If the latter conditions are not met, the prosthesis will be associated with an acute/chronic inflammatory reaction, peri-prosthetic osteolysis, loosening and failure. This article (Part 1 of 2) is dedicated to the use of metallic devices in orthopaedic surgery including the associated biological response to metallic byproducts is a review of the basic science literature regarding this topic. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  View details for DOI 10.1002/jbm.b.33734

  View details for PubMedID 27328111

• Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing. Regenerative engineering and translational medicine Gibon, E., Loi, F., Córdova, L. A., Pajarinen, J., Lin, T., Lu, L., Nabeshima, A., Yao, Z., Goodman, S. B. 2016; 2 (2): 98-104

  Abstract

  Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly.Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.

  View details for DOI 10.1007/s40883-016-0016-5

  View details for PubMedID 28138512

• The Biologic Response to Bearing Materials. Orthopaedic knowledge online Gibon, E., Goodman, S. B. 2016; 14 (6)

  Abstract

  Total joint arthroplasty (TJA) is a common and highly successful orthopaedic procedure for which surgeons can use different bearing materials. The materials used for TJA must be both biocompatible to minimize adverse local tissue reactions and robust enough to support weight bearing during common daily activities. Modern bearing materials for TJA are made from metals and their alloys, polymers, and ceramics. The orthopaedic surgeon should be knowledgeable about the biologic response to the different bearing materials used for TJA, as well as the wear by-products generated.

  View details for PubMedID 29104715

• INTRODUCTION OF NEW TECHNOLOGIES IN ORTHOPAEDIC SURGERY JBJS REVIEWS Goodman, S. B., Mihalko, W. M., Anderson, P. A., Sale, K., Bozic, K. J. 2016; 4 (5)

  Abstract

  The introduction of new devices, biologics, and combination products to the orthopaedic marketplace is increasing rapidly. The majority of these new technologies obtain clearance to market by demonstrating substantial equivalence to a predicate (previously approved device) according to the U.S. Food and Drug Administration (FDA) 510(k) process. Surgeons play a critical role in the introduction of new technologies to patients and must take a leadership role in promoting safe, efficacious, appropriate, and cost-effective care, especially for operative procedures. Surgeons should monitor and document their patients' clinical outcomes and adverse events when using new technology, to ensure that the new technology is performing as desired.

  View details for PubMedID 27490218

• Inflammation, fracture and bone repair. Bone Loi, F., Córdova, L. A., Pajarinen, J., Lin, T., Yao, Z., Goodman, S. B. 2016; 86: 119-130

  Abstract

  The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair.

  View details for DOI 10.1016/j.bone.2016.02.020

  View details for PubMedID 26946132

• The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction. Journal of biomedical materials research. Part B, Applied biomaterials Gibon, E., Córdova, L. A., Lu, L., Lin, T., Yao, Z., Hamadouche, M., Goodman, S. B. 2016

  Abstract

  Novel evidence-based prosthetic designs and biomaterials facilitate the performance of highly successful joint replacement (JR) procedures. To achieve this goal, constructs must be durable, biomechanically sound, and avoid adverse local tissue reactions. Different biomaterials such as metals and their alloys, polymers, ceramics, and composites are currently used for JR implants. This review focuses on (1) the biological response to the different biomaterials used for TJR and (2) the chronic inflammatory and foreign-body response induced by byproducts of these biomaterials. A homeostatic state of bone and surrounding soft tissue with current biomaterials for JR can be achieved with mechanically stable, infection free and intact (as opposed to the release of particulate or ionic byproducts) implants. Adverse local tissue reactions (an acute/chronic inflammatory reaction, periprosthetic osteolysis, loosening and subsequent mechanical failure) may evolve when the latter conditions are not met. This article (Part 2 of 2) summarizes the biological response to the non-metallic materials commonly used for joint replacement including polyethylene, ceramics, and polymethylmethacrylate (PMMA), as well as the foreign body reaction to byproducts of these materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  View details for DOI 10.1002/jbm.b.33676

  View details for PubMedID 27080740

• Multifunctional coatings to simultaneously promote osseointegration and prevent infection of orthopaedic implants. Biomaterials Raphel, J., Holodniy, M., Goodman, S. B., Heilshorn, S. C. 2016; 84: 301-314

  Abstract

  The two leading causes of failure for joint arthroplasty prostheses are aseptic loosening and periprosthetic joint infection. With the number of primary and revision joint replacement surgeries on the rise, strategies to mitigate these failure modes have become increasingly important. Much of the recent work in this field has focused on the design of coatings either to prevent infection while ignoring bone mineralization or vice versa, to promote osseointegration while ignoring microbial susceptibility. However, both coating functions are required to achieve long-term success of the implant; therefore, these two modalities must be evaluated in parallel during the development of new orthopaedic coating strategies. In this review, we discuss recent progress and future directions for the design of multifunctional orthopaedic coatings that can inhibit microbial cells while still promoting osseointegration.

  View details for DOI 10.1016/j.biomaterials.2016.01.016

  View details for PubMedID 26851394

• Aging, inflammation, stem cells, and bone healing STEM CELL RESEARCH & THERAPY Gibon, E., Lu, L., Goodman, S. B. 2016; 7

  Abstract

  Complex interactions among cells of the monocyte-macrophage-osteoclast lineage and the mesenchymal stem cell-osteoblast lineage play a major role in the pathophysiology of bone healing. Whereas the former lineage directs inflammatory events and bone resorption, the latter represents a source of cells for bone regeneration and immune modulation. Both of these lineages are affected by increasing age, which is associated with higher baseline levels of inflammatory mediators, and a significant reduction in osteogenic capabilities. Given the above, fracture healing, osteoporosis, and other related events in the elderly present numerous challenges, which potentially could be aided by new therapeutic approaches to modulate both inflammation and bone regeneration.

  View details for DOI 10.1186/s13287-016-0300-9

  View details for Web of Science ID 000372580800001

  View details for PubMedCentralID PMC4804630

• Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants. Biomaterials Raphel, J., Karlsson, J., Galli, S., Wennerberg, A., Lindsay, C., Haugh, M. G., Pajarinen, J., Goodman, S. B., Jimbo, R., Andersson, M., Heilshorn, S. C. 2016; 83: 269-282

  Abstract

  Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 h, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.

  View details for DOI 10.1016/j.biomaterials.2015.12.030

  View details for PubMedID 26790146

• Removal of Well-Fixed Cementless Acetabular Components in Revision Total Hip Arthroplasty. Orthopedics Adelani, M. A., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2016; 39 (2): e280-4

  Abstract

  The Zimmer Explant Acetabular Cup Removal System (Warsaw, Indiana) has been touted as a superior method for removing well-fixed cementless acetabular components while minimizing bone loss; however, no comparative data support this. This study compares bone loss following the removal of well-fixed acetabular components with Aufranc gouges and with the Explant System. A review of 623 revision total hip arthroplasties (THAs) at the authors' institution between 2002 and 2013 identified cases involving the revision of well-fixed cementless hemispherical acetabular components for any reason except infection. Twenty-four cases using Aufranc gouges and 27 cases using the Explant System were included. The following surrogates for bone loss were used: (1) the difference between the initial acetabular component outer diameter (OD) and the final reamer OD; (2) the difference between the initial acetabular component OD and the new acetabular component OD; and (3) the use of impaction bone grafting. A 2-tailed Wilcoxon-Mann-Whitney test was used to assess the difference in bone loss between the 2 groups. The use of bone grafting was compared between the groups with the chi-square test. The median differences between the initial acetabular component and the final reamer (P=.004), as well as between the initial and new acetabular components (P=.002), were 2 mm less with the Explant System. Hips in the Aufranc group were more likely to have bone grafting (54% vs 26%; P=.04). These results suggest less bone loss when removing well-fixed acetabular components with the Zimmer Explant System compared with Aufranc gouges. [Orthopedics. 2016; 39(2):e280-e284.].

  View details for DOI 10.3928/01477447-20160129-04

  View details for PubMedID 26840697

• Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Naganuma, Y., Takakubo, Y., Hirayama, T., Tamaki, Y., Pajarinen, J., Sasaki, K., Goodman, S. B., Takagi, M. 2016; 104 (2): 435-444

  Abstract

  Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased mRNA levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1β, whereas, reinforced secretion of IL-1β was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1β release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35581

  View details for Web of Science ID 000368271600011

• Is There a Benefit to Modularity in 'Simpler' Femoral Revisions? Clinical orthopaedics and related research Huddleston, J. I., Tetreault, M. W., Yu, M., Bedair, H., Hansen, V. J., Choi, H. R., Goodman, S. B., Sporer, S. M., Della Valle, C. J. 2016; 474 (2): 415-20

  Abstract

  Modular revision femoral components allow the surgeon to make more precise intraoperative adjustments in anteversion and sizing, which may afford lower dislocation rates and improved osseointegration, but may not offer distinct advantages when compared with less expensive monoblock revision stems.We compared modular and monoblock femoral components for revision of Paprosky Type I to IIIA femoral defects to determine (1) survivorship of the stems; and (2) complications denoted as intraoperative fracture, dislocation, or failure of osseointegration.Between 2004 and 2010, participating surgeons at three centers revised 416 total hip arthroplasties (THAs) with Paprosky Type I to IIIA femoral defects. Of those with minimum 2-year followup (343 THAs, mean followup 51 ± 13 months), 150 (44%) were treated with modular stems and 193 (56%) were treated with monoblock, cylindrical, fully porous-coated stems. During this time, modular stems were generally chosen when there was remodeling of the proximal femur into retroversion and/or larger canal diameters (usually > 18 mm). A total of 27 patients died (6%) with stems intact before 2 years, 46 THAs (13%) were lost to followup before 2 years for reasons other than death, and there was no differential loss to followup between the study groups. The modular stems included 101 with a cylindrical distal geometry (67%) and 49 with a tapered geometry (33%). Mean age (64 versus 68 years), percentage of women (53% versus 47%), and body mass index (31 versus 30 kg/m(2)) were not different between the two cohorts, whereas there was trend toward a slightly greater case complexity in the modular group (55% versus 65% Type 3a femoral defects, p = 0.06). Kaplan-Meier survivorship was calculated for the endpoint of aseptic revision. Proportions of complications in each cohort (dislocation, intraoperative fracture, and failure of osseointegration) were compared.Femoral component rerevision for any reason (including infection) was greater (OR, 2.01; 95% CI, 1.63-2.57; p = 0.03) in the monoblock group (27 of 193 [14%]) compared with the modular cohort (10 of 150 [7%]). Femoral component survival free from aseptic rerevision was greater in the modular group with 91% survival (95% CI, 89%-95%) at 9 years compared with 86% survival (95% CI, 83%-88%) for the monoblock group in the same timeframe. There was no difference in the proportion of mechanically relevant aseptic complications (30 of 193 [16%] in the monoblock group versus 34 of 150 [23%] in the modular group, p = 0.10; OR, 1.47; 95% CI, 0.86-2.53). There were more intraoperative fractures in the modular group (17 of 150 [11%] versus nine of 193 [5%]; OR, 2.2; 95% CI, 1.68-2.73; p = 0.02). There were no differences in the proportions of dislocation (13 of 193 [7%] monoblock versus 14 of 150 [9%] modular; OR, 0.96; 95% CI, 0.67-1.16; p = 0.48) or failure of osseointegration (eight of 193 [4%] monoblock versus three of 150 [2%] modular; OR, 1.92; 95% CI, 0.88-2.84; p = 0.19) between the two groups with the number of hips available for study.Although rerevisions were less common in patients treated with modular stems, aseptic complications such as intraoperative fractures were more common in that group, and the sample was too small to evaluate corrosion-related or fatigue concerns associated with modularity. We cannot therefore conclude from this that one design is superior to the other. Larger studies and pooled analyses will need to be performed to answer this question, but we believe modularity should be avoided in more straightforward cases if possible.Level III, therapeutic study.

  View details for DOI 10.1007/s11999-015-4474-8

  View details for PubMedID 26245164

  View details for PubMedCentralID PMC4709297

• Can a Conical Implant Successfully Address Complex Anatomy in Primary THA? Radiographs and Hip Scores at Early Followup. Clinical orthopaedics and related research Zhang, Q., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2016; 474 (2): 459-64

  Abstract

  Total hip arthroplasty (THA) in patients with small or abnormal proximal femoral anatomy is challenging as a result of complex anatomic deformities in the hip. It is unclear which stem is the most appropriate for these patients. One possible implant design that may help meet this need is the modified Wagner Cone prosthesis, whose design consists of monoblock cone with splines; however, to our knowledge, no clinical results have been published using this implant.We evaluated the hip scores and radiographic results (including signs of osseointegration and subsidence) of complex primary THA using the modified Wagner Cone cementless femoral component in patients with small or abnormal proximal femoral anatomic proportions.Between 2006 and 2011, we performed 59 THAs on patients whose femoral geometry precluded the use of standard-sized implants. Of these, 49 (83%) received the modified Wagner Cone prosthesis. During this time, our indications for use of the Wagner Cone implant in such patients included: femoral neck retroversion, excessive anteversion of the femoral neck, or small proximal femora not suitable for standard implants. Of those, 40 patients with 49 THAs were available for radiographic and clinical followup at a minimum of 3 years, and no patients were lost to followup. The diagnosis included developmental dysplasia of hip (22 patients, 28 hips), secondary trauma or posttuberculosis osteoarthritis (nine patients, 10 hips), and hip disease secondary to other disorders (eight patients, nine hips) and osteonecrosis (one patients, two hips). Two versions of the stem with 135° (28 hips) or 125° (21 hips) neck angle versions were used to reestablish normal hip biomechanics. Version angle was chosen based on preoperative templating. Cementless cups with screws were used for the acetabulum. Mean followup was 4 years (range, 3-7 years). Study endpoints were the Harris hip score and radiographic evaluations by a surgeon not involved in the clinical care of the patients (QZ); radiographic analysis included evaluating for the presence or absence of signs of osseointegration (including Engh's criteria) and subsidence.The Harris hip score improved from a mean of 41 ± 9 preoperatively to a mean of 85 ± 10 at last followup (p < 0.01). The mean vertical subsidence was 1.5 ± 1.1 mm. Radiographic evaluation demonstrated stability (no further subsidence) of all implants at last followup. Endosteal spot welds were found in 32 hips (65%). No progressive radiolucencies were observed. One patient (one hip) underwent revision surgery as a result of late infection; no other revisions were performed.The modified Wagner Cone femoral stem has provided improvements in hip scores and promising short-term radiographic results at short-term followup in complex cementless THA associated with abnormal or small femoral anatomical proportions in which standard implants are inappropriate. Longer followup will be needed to see if these results endure. Randomized trials are needed to determine the optimal stem design for these patients.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4480-x

  View details for PubMedID 26245165

  View details for PubMedCentralID PMC4709298

• Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes. Journal of biomedical materials research. Part A Naganuma, Y., Takakubo, Y., Hirayama, T., Tamaki, Y., Pajarinen, J., Sasaki, K., Goodman, S. B., Takagi, M. 2016; 104 (2): 435-444

  Abstract

  Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased mRNA levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1β, whereas, reinforced secretion of IL-1β was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1β release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35581

  View details for PubMedID 26440284

• Editorial Comment: 2015 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2016; 474 (2): 319–20

  View details for DOI 10.1007/s11999-015-4586-1

  View details for Web of Science ID 000368021900009

  View details for PubMedID 26463563

  View details for PubMedCentralID PMC4709325

• Can a Conical Implant Successfully Address Complex Anatomy in Primary THA? Radiographs and Hip Scores at Early Followup CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Zhang, Q., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2016; 474 (2): 459-464

  Abstract

  Total hip arthroplasty (THA) in patients with small or abnormal proximal femoral anatomy is challenging as a result of complex anatomic deformities in the hip. It is unclear which stem is the most appropriate for these patients. One possible implant design that may help meet this need is the modified Wagner Cone prosthesis, whose design consists of monoblock cone with splines; however, to our knowledge, no clinical results have been published using this implant.We evaluated the hip scores and radiographic results (including signs of osseointegration and subsidence) of complex primary THA using the modified Wagner Cone cementless femoral component in patients with small or abnormal proximal femoral anatomic proportions.Between 2006 and 2011, we performed 59 THAs on patients whose femoral geometry precluded the use of standard-sized implants. Of these, 49 (83%) received the modified Wagner Cone prosthesis. During this time, our indications for use of the Wagner Cone implant in such patients included: femoral neck retroversion, excessive anteversion of the femoral neck, or small proximal femora not suitable for standard implants. Of those, 40 patients with 49 THAs were available for radiographic and clinical followup at a minimum of 3 years, and no patients were lost to followup. The diagnosis included developmental dysplasia of hip (22 patients, 28 hips), secondary trauma or posttuberculosis osteoarthritis (nine patients, 10 hips), and hip disease secondary to other disorders (eight patients, nine hips) and osteonecrosis (one patients, two hips). Two versions of the stem with 135° (28 hips) or 125° (21 hips) neck angle versions were used to reestablish normal hip biomechanics. Version angle was chosen based on preoperative templating. Cementless cups with screws were used for the acetabulum. Mean followup was 4 years (range, 3-7 years). Study endpoints were the Harris hip score and radiographic evaluations by a surgeon not involved in the clinical care of the patients (QZ); radiographic analysis included evaluating for the presence or absence of signs of osseointegration (including Engh's criteria) and subsidence.The Harris hip score improved from a mean of 41 ± 9 preoperatively to a mean of 85 ± 10 at last followup (p < 0.01). The mean vertical subsidence was 1.5 ± 1.1 mm. Radiographic evaluation demonstrated stability (no further subsidence) of all implants at last followup. Endosteal spot welds were found in 32 hips (65%). No progressive radiolucencies were observed. One patient (one hip) underwent revision surgery as a result of late infection; no other revisions were performed.The modified Wagner Cone femoral stem has provided improvements in hip scores and promising short-term radiographic results at short-term followup in complex cementless THA associated with abnormal or small femoral anatomical proportions in which standard implants are inappropriate. Longer followup will be needed to see if these results endure. Randomized trials are needed to determine the optimal stem design for these patients.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4480-x

  View details for Web of Science ID 000368021900033

  View details for PubMedCentralID PMC4709298

• Is There a Benefit to Modularity in 'Simpler' Femoral Revisions? CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Huddleston, J. I., Tetreault, M. W., Yu, M., Bedair, H., Hansen, V. J., Choi, H., Goodman, S. B., Sporer, S. M., Della Valle, C. J. 2016; 474 (2): 415-420

  Abstract

  Modular revision femoral components allow the surgeon to make more precise intraoperative adjustments in anteversion and sizing, which may afford lower dislocation rates and improved osseointegration, but may not offer distinct advantages when compared with less expensive monoblock revision stems.We compared modular and monoblock femoral components for revision of Paprosky Type I to IIIA femoral defects to determine (1) survivorship of the stems; and (2) complications denoted as intraoperative fracture, dislocation, or failure of osseointegration.Between 2004 and 2010, participating surgeons at three centers revised 416 total hip arthroplasties (THAs) with Paprosky Type I to IIIA femoral defects. Of those with minimum 2-year followup (343 THAs, mean followup 51 ± 13 months), 150 (44%) were treated with modular stems and 193 (56%) were treated with monoblock, cylindrical, fully porous-coated stems. During this time, modular stems were generally chosen when there was remodeling of the proximal femur into retroversion and/or larger canal diameters (usually > 18 mm). A total of 27 patients died (6%) with stems intact before 2 years, 46 THAs (13%) were lost to followup before 2 years for reasons other than death, and there was no differential loss to followup between the study groups. The modular stems included 101 with a cylindrical distal geometry (67%) and 49 with a tapered geometry (33%). Mean age (64 versus 68 years), percentage of women (53% versus 47%), and body mass index (31 versus 30 kg/m(2)) were not different between the two cohorts, whereas there was trend toward a slightly greater case complexity in the modular group (55% versus 65% Type 3a femoral defects, p = 0.06). Kaplan-Meier survivorship was calculated for the endpoint of aseptic revision. Proportions of complications in each cohort (dislocation, intraoperative fracture, and failure of osseointegration) were compared.Femoral component rerevision for any reason (including infection) was greater (OR, 2.01; 95% CI, 1.63-2.57; p = 0.03) in the monoblock group (27 of 193 [14%]) compared with the modular cohort (10 of 150 [7%]). Femoral component survival free from aseptic rerevision was greater in the modular group with 91% survival (95% CI, 89%-95%) at 9 years compared with 86% survival (95% CI, 83%-88%) for the monoblock group in the same timeframe. There was no difference in the proportion of mechanically relevant aseptic complications (30 of 193 [16%] in the monoblock group versus 34 of 150 [23%] in the modular group, p = 0.10; OR, 1.47; 95% CI, 0.86-2.53). There were more intraoperative fractures in the modular group (17 of 150 [11%] versus nine of 193 [5%]; OR, 2.2; 95% CI, 1.68-2.73; p = 0.02). There were no differences in the proportions of dislocation (13 of 193 [7%] monoblock versus 14 of 150 [9%] modular; OR, 0.96; 95% CI, 0.67-1.16; p = 0.48) or failure of osseointegration (eight of 193 [4%] monoblock versus three of 150 [2%] modular; OR, 1.92; 95% CI, 0.88-2.84; p = 0.19) between the two groups with the number of hips available for study.Although rerevisions were less common in patients treated with modular stems, aseptic complications such as intraoperative fractures were more common in that group, and the sample was too small to evaluate corrosion-related or fatigue concerns associated with modularity. We cannot therefore conclude from this that one design is superior to the other. Larger studies and pooled analyses will need to be performed to answer this question, but we believe modularity should be avoided in more straightforward cases if possible.Level III, therapeutic study.

  View details for DOI 10.1007/s11999-015-4474-8

  View details for Web of Science ID 000368021900025

  View details for PubMedCentralID PMC4709297

• The effects of immunomodulation by macrophage subsets on osteogenesis in vitro STEM CELL RESEARCH & THERAPY Loi, F., Cordova, L. A., Zhang, R., Pajarinen, J., Lin, T., Goodman, S. B., Yao, Z. 2016; 7

  Abstract

  Bone formation and remodeling are influenced by the inflammatory state of the local microenvironment. In this regard, macrophages are postulated to play a crucial role in modulating osteogenesis. However, the differential effects of macrophage subsets and their plasticity on bone formation are currently unknown.Polarized primary murine macrophages and preosteoblastic MC3T3 cells were co-cultured to investigate the effect of non-activated M0, pro-inflammatory M1, and tissue-regenerative M2 macrophages on the osteogenic ability of MC3T3-E1 cells in vitro. Furthermore, to model the physiological transition from inflammation to tissue regeneration, M1-MC3T3 co-cultures were treated with interleukin-4 (IL-4) at different time points to modulate the M1 phenotype towards M2. Macrophage phenotypic markers were assessed by flow cytometry and enzyme-linked immunosorbent assay. A time course study of osteogenic markers at different time points was conducted: alkaline phosphatase (ALP) mRNA levels were evaluated at week 1, ALP activity and osteocalcin and osteopontin mRNA levels at week 2, and matrix mineralization and osteocalcin and osteopontin protein concentrations at week 3. Supernatant collected 72 hours after seeding or IL-4 treatment, whichever was later, was analyzed for oncostatin M, a cytokine released by macrophages that has been recognized to enhance osteogenesis. Unpaired t test or one-way ANOVA with Tukey's or Dunnett's post hoc tests were used for statistical comparison of the groups.Co-culture with any of the macrophage subtypes increased the osteogenic ability of MC3T3 cells as indicated by increases in ALP activity and matrix mineralization. Increased ALP activity, osteocalcin concentration, and matrix mineralization demonstrated that osteogenesis by M1-MC3T3 co-cultures was further enhanced by macrophage phenotype modulation to M2 via IL-4 treatment 72 hours after seeding. Increased oncostatin M protein concentration in untreated M1-MC3T3 co-cultures and M1-MC3T3 co-cultures treated with IL-4 at 72 hours correlated with greater ALP activity and matrix mineralization.These results suggest that a transient inflammatory phase is crucial for enhanced bone formation. Macrophage plasticity may offer new strategies for modulating the local inflammatory microenvironment with the aim of potentially enhancing bone repair.

  View details for DOI 10.1186/s13287-016-0276-5

  View details for Web of Science ID 000368576600001

• Treatment of Periprosthetic Knee Infection With a Two-stage Protocol Using Static Spacers CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Lichstein, P., Su, S., Hedlund, H., Suh, G., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2016; 474 (1): 120-125

  Abstract

  Two-stage exchange arthroplasty is a standard approach for treating total knee arthroplasty periprosthetic joint infection in the United States, but whether this should be performed with a static antibiotic spacer or an articulating one that allows range of motion before reimplantation remains controversial. It is unclear if the advantages of articulating spacers (easier surgical exposure during reimplantation and improved postoperative flexion) outweigh the disadvantages of increased cost and complexity in the setting of similar rates of infection eradication.The purposes of this study were (1) to determine the ultimate range of motion; and (2) to determine the proportion of patients who remained free of infection at a minimum 2 years after treatment with static antibiotic spacers as part of a two-stage revision TKA for the treatment of periprosthetic joint infection.Between 1999 and 2011, we treated 121 patients with chronically infected TKAs, of whom three had medical comorbidities precluding a two-stage exchange, four had died before 2-year followup for reasons other than the surgical intervention, and seven were lost to followup. The remaining 107 patients (109 knees; 53 men and 54 women) were treated using a two-stage approach with static spacers and are evaluated here at a mean of 3.7 years (range, 2.0-9.8 years); no patients were treated with articulating spacers during this study period. Twenty-five percent (27 of 109) of the organisms isolated the first-stage procedure were resistant to methicillin and/or vancomycin. Median age at the time of reimplantation was 67 years (range, 42-89 years). Range of motion was measured by an independent physical therapist with a standard goniometer. Knee Society knee and function scores were calculated before the first stage and at the 2-year mark. Because many of these patients were treated before consensus definitions of infection were established, we made the diagnosis of infection (and established that a patient was believed to be free of infection) using the approaches prevalent at that time, which generally included presence of a sinus tract communicating directly with the implant, two positive tissue cultures, or a combination of cultures, fluid analysis, and serology.Postoperatively, 67 knees had full extension and no patients had a flexion contracture > 10°. Median flexion was 100° (range, 60°-139°). Thirty-nine knees had postoperative flexion > 120°. Ninety-four percent of patients were clinically free of infection at last followup.Our two-stage exchange protocol with static spacers yielded comparable flexion and infection eradication when compared with other recent studies that have used articulating spacers. The large proportion of resistant organisms is alarming. Future multicenter studies should compare static with articulating spacers and should evaluate both cost and efficacy, because our study suggests that adequate range of motion can be achieved without the added cost of the articulating spacer.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4443-2

  View details for Web of Science ID 000368022600023

  View details for PubMedCentralID PMC4686492

• Treatment of Periprosthetic Knee Infection With a Two-stage Protocol Using Static Spacers. Clinical orthopaedics and related research Lichstein, P., Su, S., Hedlund, H., Suh, G., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2016; 474 (1): 120-5

  Abstract

  Two-stage exchange arthroplasty is a standard approach for treating total knee arthroplasty periprosthetic joint infection in the United States, but whether this should be performed with a static antibiotic spacer or an articulating one that allows range of motion before reimplantation remains controversial. It is unclear if the advantages of articulating spacers (easier surgical exposure during reimplantation and improved postoperative flexion) outweigh the disadvantages of increased cost and complexity in the setting of similar rates of infection eradication.The purposes of this study were (1) to determine the ultimate range of motion; and (2) to determine the proportion of patients who remained free of infection at a minimum 2 years after treatment with static antibiotic spacers as part of a two-stage revision TKA for the treatment of periprosthetic joint infection.Between 1999 and 2011, we treated 121 patients with chronically infected TKAs, of whom three had medical comorbidities precluding a two-stage exchange, four had died before 2-year followup for reasons other than the surgical intervention, and seven were lost to followup. The remaining 107 patients (109 knees; 53 men and 54 women) were treated using a two-stage approach with static spacers and are evaluated here at a mean of 3.7 years (range, 2.0-9.8 years); no patients were treated with articulating spacers during this study period. Twenty-five percent (27 of 109) of the organisms isolated the first-stage procedure were resistant to methicillin and/or vancomycin. Median age at the time of reimplantation was 67 years (range, 42-89 years). Range of motion was measured by an independent physical therapist with a standard goniometer. Knee Society knee and function scores were calculated before the first stage and at the 2-year mark. Because many of these patients were treated before consensus definitions of infection were established, we made the diagnosis of infection (and established that a patient was believed to be free of infection) using the approaches prevalent at that time, which generally included presence of a sinus tract communicating directly with the implant, two positive tissue cultures, or a combination of cultures, fluid analysis, and serology.Postoperatively, 67 knees had full extension and no patients had a flexion contracture > 10°. Median flexion was 100° (range, 60°-139°). Thirty-nine knees had postoperative flexion > 120°. Ninety-four percent of patients were clinically free of infection at last followup.Our two-stage exchange protocol with static spacers yielded comparable flexion and infection eradication when compared with other recent studies that have used articulating spacers. The large proportion of resistant organisms is alarming. Future multicenter studies should compare static with articulating spacers and should evaluate both cost and efficacy, because our study suggests that adequate range of motion can be achieved without the added cost of the articulating spacer.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4443-2

  View details for PubMedID 26280681

  View details for PubMedCentralID PMC4686492

• The Role of Macrophages in the Biological Reaction to Wear Debris from Artificial Joints. Journal of long-term effects of medical implants Nich, C. n., Takakubo, Y. n., Pajarinen, J. n., Gallo, J. n., Konttinen, Y. T., Takagi, M. n., Goodman, S. B. 2016; 26 (4): 303–9

  Abstract

  Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and eventually implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that lead to osteolysis. The biological processes involved are complex, based on the unique properties of the monocytes/macrophages, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The interaction with wear debris triggers the release of pro-inflammatory factors such as tumor necrosis factor-α, interleukin-1, and others; pro-osteoclastic factors such as RANKL; and chemokines such as MCP-1 and MIP-1, all of which are crucial to the recruitment, migration, differentiation, and ultimately activation of bone-resorbing osteoclasts. In parallel, other distinct macrophage populations inhibit inflammation and mitigate its consequences on the bone-implant interface. Here, the role of the monocyte/macrophage cell lineage in the initiation and maintenance of the host inflammatory response to wear debris and subsequent periprosthetic osteolysis is presented.

  View details for PubMedID 29199615

• Hip arthroplasty for treatment of advanced osteonecrosis: comprehensive review of implant options, outcomes and complications ORTHOPEDIC RESEARCH AND REVIEWS Waewsawangwong, W., Ruchiwit, P., Huddleston, J. I., Goodman, S. B. 2016; 8: 13–29

  View details for DOI 10.2147/ORR.S35547

  View details for Web of Science ID 000386440200001

• Comprehensive Operative Note Templates for Primary and Revision Total Hip and Knee Arthroplasty. The open orthopaedics journal Electricwala, A. J., Amanatullah, D. F., Narkbunnam, R. I., Huddleston, J. I., Maloney, W. J., Goodman, S. B. 2016; 10: 725-731

  Abstract

  Adequate preoperative planning is the first and most crucial step in the successful completion of a revision total joint arthroplasty. The purpose of this study was to evaluate the availability, adequacy and accuracy of operative notes of primary surgeries in patients requiring subsequent revision and to construct comprehensive templates of minimum necessary information required in the operative notes to further simplify re-operations, if they should become necessary.The operative notes of 144 patients (80 revision THA's and 64 revision TKA's) who underwent revision total joint arthroplasty at Stanford Hospital and Clinics in the year 2013 were reviewed. We assessed the availability of operative notes and implant stickers prior to revision total joint arthroplasty. The availability of implant details within the operative notes was assessed against the available surgical stickers for adequacy and accuracy. Statistical comparisons were made using the Fischer-exact test and a P-value of less than 0.05 was considered statistically significant.The primary operative note was available in 68 of 144 revisions (47%), 39 of 80 revision THAs (49%) and 29 of 66 revision TKAs (44%, p = 0.619). Primary implant stickers were available in 46 of 144 revisions (32%), 26 of 80 revision THAs (32%) and 20 of 66 revision TKAs (30%, p = 0.859). Utilizing the operative notes and implant stickers combined identified accurate primary implant details in only 40 of the 80 revision THAs (50%) and 34 of all 66 revision TKAs (52%, p = 0.870).Operative notes are often unavailable or fail to provide the necessary information required which makes planning and execution of revision hip and knee athroplasty difficult. This emphasizes the need for enhancing the quality of operative notes and records of patient information. Based on this information, we provide comprehensive operative note templates for primary and revision total hip and knee arthroplasty.

  View details for DOI 10.2174/1874325001610010725

  View details for PubMedID 28144382

• Aging, inflammation, stem cells, and bone healing. Stem cell research & therapy Gibon, E., Lu, L., Goodman, S. B. 2016; 7 (1): 44-?

  Abstract

  Complex interactions among cells of the monocyte-macrophage-osteoclast lineage and the mesenchymal stem cell-osteoblast lineage play a major role in the pathophysiology of bone healing. Whereas the former lineage directs inflammatory events and bone resorption, the latter represents a source of cells for bone regeneration and immune modulation. Both of these lineages are affected by increasing age, which is associated with higher baseline levels of inflammatory mediators, and a significant reduction in osteogenic capabilities. Given the above, fracture healing, osteoporosis, and other related events in the elderly present numerous challenges, which potentially could be aided by new therapeutic approaches to modulate both inflammation and bone regeneration.

  View details for DOI 10.1186/s13287-016-0300-9

  View details for PubMedID 27006071

  View details for PubMedCentralID PMC4804630

• The effects of immunomodulation by macrophage subsets on osteogenesis in vitro. Stem cell research & therapy Loi, F., Córdova, L. A., Zhang, R., Pajarinen, J., Lin, T., Goodman, S. B., Yao, Z. 2016; 7 (1): 15-?

  Abstract

  Bone formation and remodeling are influenced by the inflammatory state of the local microenvironment. In this regard, macrophages are postulated to play a crucial role in modulating osteogenesis. However, the differential effects of macrophage subsets and their plasticity on bone formation are currently unknown.Polarized primary murine macrophages and preosteoblastic MC3T3 cells were co-cultured to investigate the effect of non-activated M0, pro-inflammatory M1, and tissue-regenerative M2 macrophages on the osteogenic ability of MC3T3-E1 cells in vitro. Furthermore, to model the physiological transition from inflammation to tissue regeneration, M1-MC3T3 co-cultures were treated with interleukin-4 (IL-4) at different time points to modulate the M1 phenotype towards M2. Macrophage phenotypic markers were assessed by flow cytometry and enzyme-linked immunosorbent assay. A time course study of osteogenic markers at different time points was conducted: alkaline phosphatase (ALP) mRNA levels were evaluated at week 1, ALP activity and osteocalcin and osteopontin mRNA levels at week 2, and matrix mineralization and osteocalcin and osteopontin protein concentrations at week 3. Supernatant collected 72 hours after seeding or IL-4 treatment, whichever was later, was analyzed for oncostatin M, a cytokine released by macrophages that has been recognized to enhance osteogenesis. Unpaired t test or one-way ANOVA with Tukey's or Dunnett's post hoc tests were used for statistical comparison of the groups.Co-culture with any of the macrophage subtypes increased the osteogenic ability of MC3T3 cells as indicated by increases in ALP activity and matrix mineralization. Increased ALP activity, osteocalcin concentration, and matrix mineralization demonstrated that osteogenesis by M1-MC3T3 co-cultures was further enhanced by macrophage phenotype modulation to M2 via IL-4 treatment 72 hours after seeding. Increased oncostatin M protein concentration in untreated M1-MC3T3 co-cultures and M1-MC3T3 co-cultures treated with IL-4 at 72 hours correlated with greater ALP activity and matrix mineralization.These results suggest that a transient inflammatory phase is crucial for enhanced bone formation. Macrophage plasticity may offer new strategies for modulating the local inflammatory microenvironment with the aim of potentially enhancing bone repair.

  View details for DOI 10.1186/s13287-016-0276-5

  View details for PubMedID 26801095

• Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo. Journal of orthopaedic research Jiang, X., Sato, T., Yao, Z., Keeney, M., Pajarinen, J., Lin, T., Loi, F., Egashira, K., Goodman, S., Yang, F. 2016; 34 (1): 58-64

  Abstract

  Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade that may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.22977

  View details for PubMedID 26174978

• Pain Duration and Resolution following Surgery: An Inception Cohort Study PAIN MEDICINE Carroll, I. R., Hah, J. M., Barelka, P. L., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F. M., Mackey, S. C. 2015; 16 (12): 2386-2396

  Abstract

  Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort.We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here, we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression.Between January 2007 and April 2009, we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3-61) reduction in the rate of pain resolution (P = 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23-190) increased rate of pain resolution (P = 0.004).Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, post-traumatic stress disorder symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.

  View details for DOI 10.1111/pme.12842

  View details for Web of Science ID 000368297000020

  View details for PubMedCentralID PMC4706803

• Immune modulation as a therapeutic strategy in bone regeneration. Journal of experimental orthopaedics Schlundt, C., Schell, H., Goodman, S. B., Vunjak-Novakovic, G., Duda, G. N., Schmidt-Bleek, K. 2015; 2 (1): 1

  Abstract

  We summarize research approaches and findings on bone healing and regeneration that were presented at a workshop at the 60th annual meeting of the Orthopedic Research Society (ORS) in New Orleans in 2014. The workshop was designed to discuss the role of inflammation in bone regeneration in the context of fundamental biology, and to develop therapeutic strategies that involve immune modulation. Delayed or non-healing of bone is a major clinical problem, with around 10% of fracture patients suffering from unsatisfying healing outcomes. Inflammation is traditionally seen as a defense mechanism, but was recently found essential in supporting and modulating regenerative cascades. In bone healing, macrophages and T- and B-cells interact with progenitor cells, bone forming osteoblasts and remodeling osteoclasts. Among the cells of the innate immunity, macrophages are promising candidates for targets in immune-modulatory interventions that would overcome complications in bone healing and bone-related diseases. Among the cells of the adaptive immune system, CD8+ T cells have been shown to have a negative impact on bone fracture healing outcome, whereas regulatory T cells could be promising candidates that have a positive, modulating effect on bone fracture healing. This workshop addressed recent advances and key challenges in this exciting interdisciplinary research field.

  View details for PubMedID 26914869

• Pain Duration and Resolution following Surgery: An Inception Cohort Study. Pain medicine Carroll, I. R., Hah, J. M., Barelka, P. L., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F. M., Mackey, S. C. 2015; 16 (12): 2386-2396

  Abstract

  Preoperative determinants of pain duration following surgery are poorly understood. We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort.We conducted a prospective longitudinal study of patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain. The primary endpoint was time to opioid cessation, and those results have been previously reported. Here, we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression.Between January 2007 and April 2009, we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures. In the final multivariate model, preoperative self-perceived risk of addiction predicted more prolonged pain. Unexpectedly, anxiety sensitivity predicted more rapid pain resolution after surgery. Each one-point increase (on a four point scale) of self-perceived risk of addiction was associated with a 38% (95% CI 3-61) reduction in the rate of pain resolution (P = 0.04). Furthermore, higher anxiety sensitivity was associated with an 89% (95% CI 23-190) increased rate of pain resolution (P = 0.004).Greater preoperative self-perceived risk of addiction, and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery. Each of these factors was a better predictor of pain duration than preoperative depressive symptoms, post-traumatic stress disorder symptoms, past substance use, fear of pain, gender, age, preoperative pain, or preoperative opioid use.

  View details for DOI 10.1111/pme.12842

  View details for PubMedID 26179223

• NF-B decoy oligodeoxynucleotide inhibits wear particle-induced inflammation in a murine calvarial model JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Sato, T., Pajarinen, J., Lin, T., Tamaki, Y., Loi, F., Egashira, K., Yao, Z., Goodman, S. B. 2015; 103 (12): 3872-3878

  Abstract

  Wear particles induce periprosthetic inflammation and osteolysis through activation of Nuclear Factor kappa B (NF-κB) in macrophages, which up-regulates the downstream target gene expression for pro-inflammatory cytokines. It is hypothesized that direct suppression of NF-κB activity in the early phases of this disorder is a therapeutic strategy for mitigating the inflammatory response to wear particles, potentially mitigating osteolysis. NF-κB activity can be suppressed via competitive binding with double stranded NF-κB decoy oligodeoxynucleotides (ODNs) that block this transcription factor from binding to the promoter regions of targeted genes. In this murine calvarial study, clinically relevant polyethylene particles (PEs) with/without ODN were subcutaneously injected over the calvarial bone. In the presence of PE particles, macrophages migrated to the inflammatory site and induced tumor necrosis factor alpha (TNF-α) and Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL) expression, resulting in an increase in the number of osteoclasts. Local injections of ODN mitigated the expression of TNF-α, RANKL, and induced the expression of two anti-inflammatory, anti-resorptive cytokines: Interleukin-1 receptor antagonist (IL-1ra) and Osteoprotegerin (OPG). Local intervention with NF-κB decoy ODN in early cases of particle-induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.35532

  View details for PubMedID 26123702

• Establishment of Green Fluorescent Protein and Firefly Luciferase Expressing Mouse Primary Macrophages for In Vivo Bioluminescence Imaging PLOS ONE Pajarinen, J., Lin, T., Sato, T., Loi, F., Yao, Z., Konttinen, Y. T., Goodman, S. B. 2015; 10 (11)

  Abstract

  Macrophages play a key role in tissue homeostasis as well as in a range of pathological conditions including atherosclerosis, cancer, and autoimmunity. Many aspects of their in vivo behavior are, however, poorly understood. Bioluminescence imaging (BLI) with green fluorescent protein (GFP) and firefly luciferase (FLUC) labelled autologous reporter macrophages could potentially offer a powerful tool to study macrophage biology, but this approach has been hindered by the relative difficulty of efficient gene transfer into primary macrophages. Here we describe a straightforward method for producing large numbers of GFP/FLUC expressing mouse primary macrophages utilizing lentivirus vector, cyclosporine, and a double infection strategy. Using this method we achieved up to 60% of macrophages to express GFP with correspondingly high FLUC signal. When injected into the circulation using a mouse model of local biomaterial induced inflammation and osteolysis, macrophages were initially detectable within the lungs, followed by systemic homing to the local area of chronic inflammation in the distal femur. In addition, transduced macrophages maintained their ability to assume M1 and M2 phenotypes although the GFP/FLUC expression was altered by the polarizing signals. These reporter macrophages could prove to be valuable tools to study the role of macrophages in health and disease.

  View details for DOI 10.1371/journal.pone.0142736

  View details for Web of Science ID 000364430700164

  View details for PubMedID 26555613

• Nanocoating for biomolecule delivery using layer-by-layer self-assembly. Journal of materials chemistry. B Keeney, M., Jiang, X. Y., Yamane, M., Lee, M., Goodman, S., Yang, F. 2015; 3 (45): 8757-8770

  Abstract

  Since its introduction in the early 1990s, layer-by-layer (LbL) self-assembly of films has been widely used in the fields of nanoelectronics, optics, sensors, surface coatings, and controlled drug delivery. The growth of this industry is propelled by the ease of film manufacture, low cost, mild assembly conditions, precise control of coating thickness, and versatility of coating materials. Despite the wealth of research on LbL for biomolecule delivery, clinical translation has been limited and slow. This review provides an overview of methods and mechanisms of loading biomolecules within LbL films and achieving controlled release. In particular, this review highlights recent advances in the development of LbL coatings for the delivery of different types of biomolecules including proteins, polypeptides, DNA, particles and viruses. To address the need for co-delivery of multiple types of biomolecules at different timing, we also review recent advances in incorporating compartmentalization into LbL assembly. Existing obstacles to clinical translation of LbL technologies and enabling technologies for future directions are also discussed.

  View details for DOI 10.1039/c5tb00450k

  View details for PubMedID 27099754

  View details for PubMedCentralID PMC4835036

• Treatment of Secondary Osteonecrosis of the Knee With Local Debridement and Osteoprogenitor Cell Grafting JOURNAL OF ARTHROPLASTY Goodman, S. B., Hwang, K. L. 2015; 30 (11): 1892-1896

  Abstract

  Secondary osteonecrosis of the knee (SOK) affects young individuals with chronic diseases and corticosteroid use. We report a series of young patients in whom the osteonecrotic lesion was openly debrided, and concentrated bone marrow osteoprogenitor cells (OPCs) harvested from the iliac crest were placed in the defect. Twelve patients (fourteen knees) have undergone debridement and grafting of distal femoral osteonecrotic lesions. Age at surgery averaged 23 years. Follow-up averaged 5 years. None of the patients have undergone further surgery, or were taking medications for ipsilateral knee pain. Knee Society Score and Knee Function Score averaged 87 and 85 respectively. The technique of open debridement and osteoprogenitor cell grafting for SOK is relatively simple, efficacious, has low morbidity, and does not preclude future interventions.

  View details for DOI 10.1016/j.arth.2015.05.013

  View details for PubMedID 26067706

• Musculoskeletal regeneration research network: A global initiative JOURNAL OF ORTHOPAEDIC TRANSLATION Chan, K., Rolf, C. G., Qin, L., Fellaender-Tsai, L., Castelein, R. M., Saris, D. F., Malda, J., Richards, G., Goodman, S. B., Tuan, R. S., Maloney, W., Lidgren, L., Hopkins, C., Fu, S., Li, G., Ding, M., Tang, T., Zhang, X., Wei, L., Sun, H. B., Ouyang, H. 2015; 3 (4): 160–65

  View details for PubMedID 30035054

• Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps. Journal of biomedical materials research. Part A Pajarinen, J., Tamaki, Y., Antonios, J. K., Lin, T., Sato, T., Yao, Z., Takagi, M., Konttinen, Y. T., Goodman, S. B. 2015; 103 (4): 1339-1345

  Abstract

  Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.

  View details for DOI 10.1002/jbm.a.35278

  View details for PubMedID 25044942

• Yrjö tapio konttinen 1952-2014. Acta orthopaedica Pajarinen, J., Nordström, D., Nordström, D., Petterson, T., Ainola, M., Gómez-Barrena, E., Takagi, M., Goodman, S. B. 2015; 86 (2): 145-146

  View details for DOI 10.3109/17453674.2015.1022103

  View details for PubMedID 25708854

  View details for PubMedCentralID PMC4404763

• Interaction Between Osteoarthritic Chondrocytes and Adipose-Derived Stem Cells Is Dependent on Cell Distribution in Three-Dimension and Transforming Growth Factor-ß3 Induction. Tissue engineering. Part A Lai, J. H., Rogan, H., Kajiyama, G., Goodman, S. B., Smith, R. L., Maloney, W., Yang, F. 2015; 21 (5-6): 992-1002

  Abstract

  Stem cells hold great promise for treating cartilage degenerative diseases such as osteoarthritis (OA). The efficacy of stem cell-based therapy for cartilage repair is highly dependent on their interactions with local cells in the joint. This study aims at evaluating the interactions between osteoarthritic chondrocytes (OACs) and adipose-derived stem cells (ADSCs) using three dimensional (3D) biomimetic hydrogels. To examine the effects of cell distribution on such interactions, ADSCs and OACs were co-cultured in 3D using three co-culture models: conditioned medium (CM), bi-layered, and mixed co-culture with varying cell ratios. Furthermore, the effect of transforming growth factor (TGF)-β3 supplementation on ADSC-OAC interactions and the resulting cartilage formation was examined. Outcomes were analyzed using quantitative gene expression, cell proliferation, cartilage matrix production, and histology. TGF-β3 supplementation led to a substantial increase in cartilage matrix depositions in all groups, but had differential effects on OAC-ADSC interactions in different co-culture models. In the absence of TGF-β3, CM or bi-layered co-culture had negligible effects on gene expression or cartilage formation. With TGF-β3 supplementation, CM and bi-layered co-culture inhibited cartilage formation by both ADSCs and OACs. In contrast, a mixed co-culture with moderate OAC ratios (25% and 50%) resulted in synergistic interactions with enhanced cartilage matrix deposition and reduced catabolic marker expression. Our results suggested that the interaction between OACs and ADSCs is highly dependent on cell distribution in 3D and soluble factors, which should be taken into consideration when designing stem cell-based therapy for treating OA patients.

  View details for DOI 10.1089/ten.TEA.2014.0244

  View details for PubMedID 25315023

• A Rare Case of Pseudotumor Formation following Total Knee Arthroplasty MALAYSIAN ORTHOPAEDIC JOURNAL Suresh, S., Pirapat, R., Goodman, S. B. 2015; 9 (1): 44–46

  View details for DOI 10.5704/MOJ.1503.014

  View details for Web of Science ID 000450590100013

• A Rare Case of Pseudotumor Formation following Total Knee Arthroplasty. Malaysian orthopaedic journal Sivananthan, S., Pirapat, R., Goodman, S. B. 2015; 9 (1): 44-46

  Abstract

  A 59 year old man who had undergone left total knee arthroplasty in 2008 presented with a 5 month history of left knee pain and persistent swelling. Workup for infection was negative and the patient was suspected to be suffering from particle disease and chronic synovitis. Imaging revealed an internally rotated tibial component. Intraoperative findings revealed extensive polyethylene wear with resultant metalon- metal articulation, soft tissue metallosis and a pseudotumor like mass at the posterolateral aspect of the popliteal fossa. This was extensively debrided and revision knee arthroplasty was performed. Suboptimal component alignment can lead to localized high loading, wear and metallosis, which in this case resulted in the formation of a pseudotumor.

  View details for DOI 10.5704/MOJ.1503.014

  View details for PubMedID 28435598

• Implant Survival and Patient-Reported Outcomes After Total Hip Arthroplasty in Young Patients With Juvenile Idiopathic Arthritis JOURNAL OF ARTHROPLASTY Swarup, I., Lee, Y., Christoph, E. I., Mandl, L. A., Goodman, S. M., Figgie, M. P. 2015; 30 (3): 398-402

  Abstract

  Juvenile Idiopathic Arthritis (JIA) is a common rheumatologic disease that frequently involves the hip joint and requires treatment with total hip arthroplasty (THA). A retrospective study with prospective follow-up was conducted to determine implant survival and patient-reported outcomes in JIA patients aged 35 or younger treated with THA. This study included 56 patients, and the mean time to follow-up was 12 years. The 10-year implant survival was 85%, and implant survival was significantly longer in older patients (P value=0.04). Hip disability and osteoarthritis outcome (HOOS) scores were favorable at follow-up, but significantly worse in women and patients with custom implants or history of revision THA. Overall, patient factors and implant characteristics predict implant survival and outcomes after THA in young patients with JIA.

  View details for DOI 10.1016/j.arth.2014.09.018

  View details for Web of Science ID 000353503500016

  View details for PubMedID 25449584

• NF-?B Decoy Oligodeoxynucleotide Enhanced Osteogenesis in Mesenchymal Stem Cells Exposed to Polyethylene Particle. Tissue engineering. Part A Lin, T., Sato, T., Barcay, K. R., Waters, H., Loi, F., Zhang, R., Pajarinen, J., Egashira, K., Yao, Z., Goodman, S. B. 2015; 21 (5-6): 875-883

  Abstract

  Excessive generation of wear particles after total joint replacement may lead to local inflammation and periprosthetic osteolysis. Modulation of the key transcription factor NF-κB in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultra-high molecular weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-κB signaling pathway on osteoprogenitor/mesenchymal stem cells (MSCs) remain unclear. Here we showed that decoy oligodeoxynucleotide (ODN) increased cell viability when primary murine MSCs were exposed to UHMWPE particles, but had no effects on cellular apoptosis. Decoy ODN increased TGF-β1 and osteoprotegerin in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN up-regulated osteoprotegerin expression through a TGF-β1 dependent pathway. By measuring alkaline phosphatase activity, osteocalcin levels, Runx2 and osteopontin expression, and performing a bone mineralization assay, we found that decoy ODN increased MSC osteogenic ability when the cells were exposed to UHMWPE particles. Furthermore, the cellular response to decoy ODN and UHMWPE particles with regards to cell phenotype, cell viability and osteogenic ability were confirmed using primary human MSCs. Our results suggest that modulation of wear particle induced inflammation by NF-κB decoy ODN had no adverse effects on MSCs, and may potentially further mitigate peri-prosthetic osteolysis by protecting MSC viability and osteogenic ability.

  View details for DOI 10.1089/ten.TEA.2014.0144

  View details for PubMedID 25518013

• Collagen VI Enhances Cartilage Tissue Generation by Stimulating Chondrocyte Proliferation. Tissue engineering. Part A Smeriglio, P., Dhulipala, L., Lai, J. H., Goodman, S. B., Dragoo, J. L., Smith, R. L., Maloney, W. J., Yang, F., Bhutani, N. 2015; 21 (3-4): 840-849

  Abstract

  Regeneration of human cartilage is inherently inefficient. Current cell-based approaches for cartilage repair, including autologous chondrocytes, are limited by the paucity of cells, associated donor site morbidity, and generation of functionally inferior fibrocartilage rather than articular cartilage. Upon investigating the role of collagen VI (Col VI), a major component of the chondrocyte pericellular matrix (PCM), we observe that soluble Col VI stimulates chondrocyte proliferation. Interestingly, both adult and osteoarthritis chondrocytes respond to soluble Col VI in a similar manner. The proliferative effect is, however, strictly due to the soluble Col VI as no proliferation is observed upon exposure of chondrocytes to immobilized Col VI. Upon short Col VI treatment in 2D monolayer culture, chondrocytes maintain high expression of characteristic chondrocyte markers like Col2a1, agc, and Sox9 whereas the expression of the fibrocartilage marker Collagen I (Col I) and of the hypertrophy marker Collagen X (Col X) is minimal. Additionally, Col VI-expanded chondrocytes show a similar potential to untreated chondrocytes in engineering cartilage in 3D biomimetic hydrogel constructs. Our study has, therefore, identified soluble Col VI as a biologic that can be useful for the expansion and utilization of scarce sources of chondrocytes, potentially for autologous chondrocyte implantation. Additionally, our results underscore the importance of further investigating the changes in chondrocyte PCM with age and disease and the subsequent effects on chondrocyte growth and function.

  View details for DOI 10.1089/ten.TEA.2014.0375

  View details for PubMedID 25257043

• Editorial Comment: 2014 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2015; 473 (2): 430–31

  View details for PubMedID 25256622

• Comparative potential of juvenile and adult human articular chondrocytes for cartilage tissue formation in three-dimensional biomimetic hydrogels. Tissue engineering. Part A Smeriglio, P., Lai, J. H., Dhulipala, L., Behn, A. W., Goodman, S. B., Smith, R. L., Maloney, W. J., Yang, F., Bhutani, N. 2015; 21 (1-2): 147-155

  Abstract

  Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, as well as embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old and diseased chondrocytes, here we examined cartilage formation by juvenile, adult and OA chondrocytes in 3D biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and GAG accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair.

  View details for DOI 10.1089/ten.TEA.2014.0070

  View details for PubMedID 25054343

• Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty BIOMED RESEARCH INTERNATIONAL Mitchelson, A. J., Wilson, C. J., Mihalko, W. M., Grupp, T. M., Manning, B. T., Dennis, D. A., Goodman, S. B., Tzeng, T. H., Vasdev, S., Saleh, K. J. 2015: 137287

  Abstract

  The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.

  View details for PubMedID 25883940

• The Use of Porous Tantalum for Reconstructing Bone Loss in Orthopedic Surgery ADVANCES IN METALLIC BIOMATERIALS: TISSUES, MATERIALS AND BIOLOGICAL REACTIONS Patil, N., Goodman, S. B., Niinomi, M., Narushima, T., Nakai, M. 2015; 3: 223–43

  View details for DOI 10.1007/978-3-662-46836-4_10

  View details for Web of Science ID 000368067000011

• Identification of periprosthetic joint infection after total hip arthroplasty JOURNAL OF ORTHOPAEDIC TRANSLATION Lee, K., Goodman, S. B. 2015; 3 (1): 21–25

  Abstract

  Although total hip arthroplasty (THA) is accepted as one of the most successful surgical procedures in orthopaedic surgery, periprosthetic joint infection after THA continues to be one of the most devastating complications. However, accurate preoperative identification of periprosthetic joint infection in patients presenting with joint pain or radiographic periprosthetic lucencies is often difficult, even after a comprehensive work-up. The purpose of this article is to review the diagnostic options available to improve the management and results of this potentially catastrophic complication.

  View details for PubMedID 30035036

• Factors Associated with Opioid Use in a Cohort of Patients Presenting for Surgery. Pain research and treatment Hah, J. M., Sharifzadeh, Y., Wang, B. M., Gillespie, M. J., Goodman, S. B., Mackey, S. C., Carroll, I. R. 2015; 2015: 829696-?

  Abstract

  Objectives. Patients taking opioids prior to surgery experience prolonged postoperative opioid use, worse clinical outcomes, increased pain, and more postoperative complications. We aimed to compare preoperative opioid users to their opioid naïve counterparts to identify differences in baseline characteristics. Methods. 107 patients presenting for thoracotomy, total knee replacement, total hip replacement, radical mastectomy, and lumpectomy were investigated in a cross-sectional study to characterize the associations between measures of pain, substance use, abuse, addiction, sleep, and psychological measures (depressive symptoms, Posttraumatic Stress Disorder symptoms, somatic fear and anxiety, and fear of pain) with opioid use. Results. Every 9-point increase in the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) score was associated with 2.37 (95% CI 1.29-4.32) increased odds of preoperative opioid use (p = 0.0005). The SOAPP-R score was also associated with 3.02 (95% CI 1.36-6.70) increased odds of illicit preoperative opioid use (p = 0.007). Also, every 4-point increase in baseline pain at the future surgical site was associated with 2.85 (95% CI 1.12-7.27) increased odds of legitimate preoperative opioid use (p = 0.03). Discussion. Patients presenting with preoperative opioid use have higher SOAPP-R scores potentially indicating an increased risk for opioid misuse after surgery. In addition, legitimate preoperative opioid use is associated with preexisting pain.

  View details for DOI 10.1155/2015/829696

  View details for PubMedID 26881072

• Nanocoating for biomolecule delivery using layer-by-layer self-assembly JOURNAL OF MATERIALS CHEMISTRY B Keeney, M., Jiang, X. Y., Yamane, M., Lee, M., Goodman, S., Yang, F. 2015; 3 (45): 8757-8770

  Abstract

  Since its introduction in the early 1990s, layer-by-layer (LbL) self-assembly of films has been widely used in the fields of nanoelectronics, optics, sensors, surface coatings, and controlled drug delivery. The growth of this industry is propelled by the ease of film manufacture, low cost, mild assembly conditions, precise control of coating thickness, and versatility of coating materials. Despite the wealth of research on LbL for biomolecule delivery, clinical translation has been limited and slow. This review provides an overview of methods and mechanisms of loading biomolecules within LbL films and achieving controlled release. In particular, this review highlights recent advances in the development of LbL coatings for the delivery of different types of biomolecules including proteins, polypeptides, DNA, particles and viruses. To address the need for co-delivery of multiple types of biomolecules at different timing, we also review recent advances in incorporating compartmentalization into LbL assembly. Existing obstacles to clinical translation of LbL technologies and enabling technologies for future directions are also discussed.

  View details for DOI 10.1039/c5tb00450k

  View details for Web of Science ID 000365012700001

  View details for PubMedCentralID PMC4835036

• Establishment of Green Fluorescent Protein and Firefly Luciferase Expressing Mouse Primary Macrophages for In Vivo Bioluminescence Imaging. PloS one Pajarinen, J., Lin, T., Sato, T., Loi, F., Yao, Z., Konttinen, Y. T., Goodman, S. B. 2015; 10 (11)

  Abstract

  Macrophages play a key role in tissue homeostasis as well as in a range of pathological conditions including atherosclerosis, cancer, and autoimmunity. Many aspects of their in vivo behavior are, however, poorly understood. Bioluminescence imaging (BLI) with green fluorescent protein (GFP) and firefly luciferase (FLUC) labelled autologous reporter macrophages could potentially offer a powerful tool to study macrophage biology, but this approach has been hindered by the relative difficulty of efficient gene transfer into primary macrophages. Here we describe a straightforward method for producing large numbers of GFP/FLUC expressing mouse primary macrophages utilizing lentivirus vector, cyclosporine, and a double infection strategy. Using this method we achieved up to 60% of macrophages to express GFP with correspondingly high FLUC signal. When injected into the circulation using a mouse model of local biomaterial induced inflammation and osteolysis, macrophages were initially detectable within the lungs, followed by systemic homing to the local area of chronic inflammation in the distal femur. In addition, transduced macrophages maintained their ability to assume M1 and M2 phenotypes although the GFP/FLUC expression was altered by the polarizing signals. These reporter macrophages could prove to be valuable tools to study the role of macrophages in health and disease.

  View details for DOI 10.1371/journal.pone.0142736

  View details for PubMedID 26555613

• Exposure of polyethylene particles induces interferon-? expression in a natural killer T lymphocyte and dendritic cell coculture system in vitro: a preliminary study. Journal of biomedical materials research. Part A Lin, T., Kao, S., Sato, T., Pajarinen, J., Zhang, R., Loi, F., Goodman, S. B., Yao, Z. 2015; 103 (1): 71-75

  Abstract

  Two major issues in total joint arthroplasty are loosening of implants and osteolysis caused by wear particle-induced inflammation. Wear particles stimulate the release of pro-inflammatory cytokines, chemokines and other inflammatory mediators from macrophages and other cells. Although the biological response of macrophages to wear debris is well established, the role of other cell types such as natural killer T lymphocytes (NKT) and dendritic cells (DCs) is limited. Here we show that ultra-high molecular weight polyethylene (UHMWPE) particles stimulate NKT cells to secrete Interferon-γ (IFN-γ); co-culture with DCs further enhanced IFN-γ secretion. Furthermore, UHMWPE particles did not stimulate NKT cells to secrete IL-4, while the NKT cell natural ligand α -Galactosylceramide (α-GalCer) treatment in the co-culture system significantly enhanced both IFN-γ and IL-4 expression by NKT cells. Comparatively, NKT cells and/or DCs exposed to polymethylmethacrylate particles did not stimulate Interferon-γ or IL-4 expression. Mouse bone marrow derived macrophage polarization by lipopolysaccharide and conditioned medium from NKT cells and/or DCs exposed to UHMWPE particles increased TNF-α, but reduced arginase-1 expression in macrophages. The current findings indicate that UHMWPE particles stimulate NKT cells/DCs to produce pro-inflammatory cytokines; this pathway is a novel therapeutic target to mitigate wear particle induced peri-prosthetic osteolysis.

  View details for DOI 10.1002/jbm.a.35159

  View details for PubMedID 24616165

• Exposure of polyethylene particles induces interferon-gamma expression in a natural killer T lymphocyte and dendritic cell coculture system in vitro: A preliminary study JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Lin, T., Kao, S., Sato, T., Pajarinen, J., Zhang, R., Loi, F., Goodman, S. B., Yao, Z. 2015; 103 (1): 71-75

  Abstract

  Two major issues in total joint arthroplasty are loosening of implants and osteolysis caused by wear particle-induced inflammation. Wear particles stimulate the release of pro-inflammatory cytokines, chemokines and other inflammatory mediators from macrophages and other cells. Although the biological response of macrophages to wear debris is well established, the role of other cell types such as natural killer T lymphocytes (NKT) and dendritic cells (DCs) is limited. Here we show that ultra-high molecular weight polyethylene (UHMWPE) particles stimulate NKT cells to secrete Interferon-γ (IFN-γ); co-culture with DCs further enhanced IFN-γ secretion. Furthermore, UHMWPE particles did not stimulate NKT cells to secrete IL-4, while the NKT cell natural ligand α -Galactosylceramide (α-GalCer) treatment in the co-culture system significantly enhanced both IFN-γ and IL-4 expression by NKT cells. Comparatively, NKT cells and/or DCs exposed to polymethylmethacrylate particles did not stimulate Interferon-γ or IL-4 expression. Mouse bone marrow derived macrophage polarization by lipopolysaccharide and conditioned medium from NKT cells and/or DCs exposed to UHMWPE particles increased TNF-α, but reduced arginase-1 expression in macrophages. The current findings indicate that UHMWPE particles stimulate NKT cells/DCs to produce pro-inflammatory cytokines; this pathway is a novel therapeutic target to mitigate wear particle induced peri-prosthetic osteolysis.

  View details for DOI 10.1002/jbm.a.35159

  View details for Web of Science ID 000345572100009

• What is the Trouble With Trunnions? CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Esposito, C. I., Wright, T. M., Goodman, S. B., Berry, D. J. 2014; 472 (12): 3652-3658

  Abstract

  Recent studies have attributed adverse local tissue reactions (ALTRs) in patients with total hip arthroplasties (THAs) to tribocorrosion debris generated by modular femoral stems. The presentations of ALTR are diverse, as are the causes of it, and the biological responses can be important reasons for failure after THA.(1) What clinical problems have been reported in patients with modular stems since 1988? (2) What THA design features are associated with tribocorrosion in taper junctions? (3) What are the microscopic and tribological characteristics of the debris produced at the taper junctions? (4) What are the cellular and immunological traits of the biological response to taper tribocorrosion debris?We conducted a systematic review using MEDLINE and EMBASE-cited articles to summarize failure modes associated with modular femoral stems. One hundred sixty-two of 1043 articles reported on the clinical performances or failure modes attributed to modular femoral stems. There were 10 laboratory studies, 26 case reports, 13 Level IV, 94 Level III, 18 Level II, and one Level I of Evidence papers. To address the remaining questions, we did a second review of 524 articles. One hundred twenty-seven articles met the eligibility criteria, including 81 articles on design features related to tribocorrosion, 15 articles on corrosion debris characteristics, and 31 articles on the biological response to tribocorrosion debris.Sixty-eight of 162 studies reported failure attributed to modular femoral stems for one of these four modularity-related failure modes: tribocorrosion-associated ALTR, dissociation of a taper junction, stem fracture, and mismatch of a femoral head taper attached to a stem with a different trunnion size. The remaining 94 studies found no clinical consequences related to the presence of a taper junction. THA component features associated with tribocorrosion included trunnion geometry and large-diameter femoral heads. Solid tribocorrosion debris is primarily chromium-orthophosphate material of variable size and may be more biologically reactive than wear debris.There has been an increase in publications describing ALTR around modular hip prostheses in the last 3 years. Implant design changes, including larger femoral heads and smaller trunnions, have been implicated, but there may also be more recognition of the problem by the orthopaedic community. Analyzing retrieved implants to understand the history of taper-related problems, designing clinically relevant in vitro corrosion tests to test modular junctions, and identifying biomarkers to recognize patients at risk of ALTR should be the focus of ongoing research to help surgeons avoid and detect tribocorrosion-related problems in joint replacements.

  View details for DOI 10.1007/s11999-014-3746-z

  View details for Web of Science ID 000344647200010

  View details for PubMedID 24980639

  View details for PubMedCentralID PMC4397760

• Editorial Comment: ABJS Carl T. Brighton Workshop on Implant Wear and Tribocorrosion of Total Joint Replacements CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Wright, T. M. 2014; 472 (12): 3650–51

  View details for PubMedID 25267269

• Total knee arthroplasty in patients with ipsilateral fused hip: a technical note. Clinics in orthopedic surgery Goodman, S. B., Huddleston, J. I., Hur, D., Song, S. J. 2014; 6 (4): 476-479

  Abstract

  We report the surgical technique used to perform posterior-stabilized total knee arthroplasty (TKA) in two patients with a well positioned and functional hip arthrodesis. Intraoperatively, the operating table was placed in an increased Trendelenburg position. Episodically, we flexed the foot of the table by 90° to allow maximal knee flexion to facilitate exposure and bone cuts. We opted to resect the patella and tibia first to enable exposure, given the stiffness of the arthritic knee. One patient's medical condition prohibited complex conversion total hip arthroplasty (THA) prior to the TKA. The other patient's scarred soft tissues around the hip, due to chronic infection and multiple operations, made THA risky. The final outcome provided satisfactory results at a minimum of 2 years postoperatively. TKA can be successfully performed with adjustments of table position and modification of the sequence of surgical steps in patients with ipsilateral hip fusion.

  View details for DOI 10.4055/cios.2014.6.4.476

  View details for PubMedID 25436074

• Interaction of Materials and Biology in Total Joint Replacement - Successes, Challenges and Future Directions. Journal of materials chemistry. B, Materials for biology and medicine Pajarinen, J., Lin, T., Sato, T., Yao, Z., Goodman, S. 2014; 2 (41): 7094-7108

  Abstract

  Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function.

  View details for DOI 10.1039/C4TB01005A

  View details for PubMedID 25541591

  View details for PubMedCentralID PMC4273175

• Clinical recovery from surgery correlates with single-cell immune signatures SCIENCE TRANSLATIONAL MEDICINE Gaudilliere, B., Fragiadakis, G. K., Bruggner, R. V., Nicolau, M., Finck, R., Tingle, M., Silva, J., Ganio, E. A., Yeh, C. G., Maloney, W. J., Huddleston, J. I., Goodman, S. B., Davis, M. M., Bendall, S. C., Fantl, W. J., Angst, M. S., Nolan, G. P. 2014; 6 (255)

  Abstract

  Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with STAT3 (signal transducer and activator of transcription), CREB (adenosine 3',5'-monophosphate response element-binding protein), and NF-κB (nuclear factor κB) signaling responses in subsets of CD14(+) monocytes (R = 0.7 to 0.8, false discovery rate <0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery.

  View details for DOI 10.1126/scitranslmed.3009701

  View details for Web of Science ID 000343316800006

• Clinical recovery from surgery correlates with single-cell immune signatures. Science translational medicine Gaudillière, B., Fragiadakis, G. K., Bruggner, R. V., Nicolau, M., Finck, R., Tingle, M., Silva, J., Ganio, E. A., Yeh, C. G., Maloney, W. J., Huddleston, J. I., Goodman, S. B., Davis, M. M., Bendall, S. C., Fantl, W. J., Angst, M. S., Nolan, G. P. 2014; 6 (255): 255ra131-?

  Abstract

  Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with STAT3 (signal transducer and activator of transcription), CREB (adenosine 3',5'-monophosphate response element-binding protein), and NF-κB (nuclear factor κB) signaling responses in subsets of CD14(+) monocytes (R = 0.7 to 0.8, false discovery rate <0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery.

  View details for DOI 10.1126/scitranslmed.3009701

  View details for PubMedID 25253674

• Characterization of Macrophage Polarizing Cytokines in the Aseptic Loosening of Total Hip Replacements JOURNAL OF ORTHOPAEDIC RESEARCH Jamsen, E., Kouri, V., Olkkonen, J., Coer, A., Goodman, S. B., Konttinen, Y. T., Pajarinen, J. 2014; 32 (9): 1241-1246

  Abstract

  Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT-PCR, the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN-γ or IL-4 could be identified. IL-17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up-regulation of IL-10, M-CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF-α, IL-1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri-implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  View details for DOI 10.1002/jor.22658

  View details for Web of Science ID 000340587200021

• Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements. Journal of orthopaedic research Jämsen, E., Kouri, V., Olkkonen, J., Cör, A., Goodman, S. B., Konttinen, Y. T., Pajarinen, J. 2014; 32 (9): 1241-1246

  Abstract

  Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT-PCR, the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN-γ or IL-4 could be identified. IL-17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up-regulation of IL-10, M-CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF-α, IL-1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri-implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

  View details for DOI 10.1002/jor.22658

  View details for PubMedID 24897980

• Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Valladares, R. D., Nich, C., Zwingenberger, S., Li, C., Swank, K. R., Gibon, E., Rao, A. J., Yao, Z., Goodman, S. B. 2014; 102 (9): 3004-3011

  Abstract

  Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure.

  View details for DOI 10.1002/jbm.a.34972

  View details for PubMedID 24115330

• Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles. Journal of biomedical materials research. Part A Yao, Z., Keeney, M., Lin, T., Pajarinen, J., Barcay, K., Waters, H., Egashira, K., Yang, F., Goodman, S. 2014; 102 (9): 3291-3297

  Abstract

  Wear particles generated from total joint replacements can stimulate macrophages to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which is the most important chemokine regulating systemic and local cell trafficking and infiltration of monocyte/macrophages in chronic inflammation. One possible strategy to curtail the adverse events associated with wear particles is to mitigate migration and activation of monocyte/macrophages. The purpose of this study is to modulate the adverse effects of particulate biomaterials and inflammatory stimuli such as endotoxin by interfering with the biological effects of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP-1-induced migration of THP-1 cells in cell migration experiments in a dose-dependent manner. Conditioned media from murine macrophages exposed to clinically relevant polymethylmethacrylate (PMMA) particles with/without endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine production was mitigated when macrophages were exposed to PMMA particles with/without LPS in the presence of 7ND. Our studies confirm that the MCP-1 mutant protein 7ND can decrease macrophage migration and inflammatory cytokine release without adverse effects at the doses tested. Local delivery of 7ND at the implant site may provide a therapeutic strategy to diminish particle-associated periprosthetic inflammation and osteolysis. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34981

  View details for PubMedID 24123855

• Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-?B decoy oligodeoxynucleotide: A preliminary report. Acta biomaterialia Lin, T., Yao, Z., Sato, T., Keeney, M., Li, C., Pajarinen, J., Yang, F., Egashira, K., Goodman, S. B. 2014; 10 (8): 3747-3755

  Abstract

  Total joint replacement (TJR) is a very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate especially because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to peri-prosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical trials, due to compensatory upregulation of other pro-inflammatory factors. We hypothesized that targeting the important transcription factor NF-κB could mitigate the inflammatory response to wear particles, potentially diminishing osteolysis. In the current study, we suppressed NF-κB activity in mouse RAW264.7 and human THP1 macrophage cell lines, as well as primary mouse and human macrophages, via competitive binding with double strand decoy oligodeoxynucleotide (ODN) containing an NF-κB binding element. We found that macrophage exposure to UHMWPE particles induced multiple pro-inflammatory cytokine and chemokine expression including TNF-α, MCP1, MIP1α and others. Importantly, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, and resulted in suppression of macrophage recruitment. The strategic use of decoy NF-κB ODN, delivered locally, could potentially diminish particle-induced peri-prosthetic osteolysis.

  View details for DOI 10.1016/j.actbio.2014.04.034

  View details for PubMedID 24814879

• Current Modes of Failure in TKA: Infection, Instability, and Stiffness Predominate. Clinical orthopaedics and related research Le, D. H., Goodman, S. B., Maloney, W. J., Huddleston, J. I. 2014; 472 (7): 2197-2200

  Abstract

  Historically, polyethylene wear and its sequelae (osteolysis, late instability, aseptic loosening) were common causes for revision total knee arthroplasty (TKA). Recently, polyethylene manufacturing has become more consistent; furthermore, a clearer understanding of the importance of oxidation on polyethylene performance led to packaging of the polyethylene bearings in an inert environment. This improved the quality and consistency of polyethylene used in TKA, raising the question of whether different failure modes now predominate after TKA.The purpose of this study was to determine the current reasons for (1) early and (2) late failures after TKA at one high-volume arthroplasty center.We reviewed all first-time revision TKAs performed between 2001 and 2011 at one institution, yielding a group of 253 revision TKAs in 251 patients. Mean age at the time of revision was 64 years (SD 10 years). Mean time to revision was 35 months (SD 23 months). Preoperative evaluations, laboratory data, radiographs, and intraoperative findings were used to determine causes for revision. Early failure was defined as revision within 2 years of the index procedure. The primary failure mechanism was determined by the operating surgeon.Early failure accounted for 46% (116 of 253) of all revisions with infection (28 of 116 [24%]), instability (30 of 116 [26%]), and stiffness (21 of 116 [18%]) being the leading causes. Late failure accounted for 54% (137 of 253) of all revisions with the most common causes including infection (34 of 137 [25%]), instability (24 of 137 [18%]), and stiffness (19 of 253 [14%]). Polyethylene wear was implicated as the failure mechanism in 2% of early cases (two of 116) and 9% of late cases (13 of 137).In contrast to previous studies, wear-related implant failure in TKA was relatively uncommon in this series. Changes in polyethylene manufacturing, sterilization, and storage may have accounted for some of this difference; however, longer-term followup will be required to verify this finding. Infection, instability, and stiffness represent the most common causes of early and late failure. Strategies to improve outcomes in TKA should be aimed at infection prophylaxis and treatment, surgical technique, and patient selection.Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-014-3540-y

  View details for PubMedID 24615421

• Polyethylene wear and osteolysis is associated with high revision rate of a small sized porous coated THA in patients with hip dysplasia. journal of arthroplasty Murray, P. J., Hwang, K. L., Imrie, S. N., Huddleston, J. I., Goodman, S. B. 2014; 29 (7): 1373-1377

  Abstract

  The outcome of 25 primary THAs in patients with hip dysplasia using the AML Bantam femoral stem (DePuy) is reported. Age at operation averaged 43 ± 10 years. Twenty-two of 25 stems were cementless. All cementless acetabular components had conventional or cross-linked polyethylene and screws. Follow-up averaged 11 ± 5 years (range 4-18). Four cementless stems were revised after 3, 4, 8, and 9 years; 2/3 cemented stems were revised at 8 and 18 years. Femoral revisions demonstrated extensive conventional polyethylene wear, periprosthetic osteolysis and loosening. Five entire cups were revised for wear and loosening; four liners were replaced. Harris Hip Scores for patients with retained stems went from 43 ± 12 to 85 ± 13. High revision rates with the proximally porous coated Bantam stem are due to loss of fixation, often associated with polyethylene wear and osteolysis.

  View details for DOI 10.1016/j.arth.2014.02.027

  View details for PubMedID 24698818

• Self-Loathing Aspects of Depression Reduce Postoperative Opioid Cessation Rate PAIN MEDICINE Hah, J. M., Mackey, S., Barelka, P. L., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F. M., Schmidt, P. C., Carroll, I. R. 2014; 15 (6): 954-964

  Abstract

  We previously reported that increased preoperative Beck Depression Inventory II (BDI-II) scores were associated with a 47% (95% CI 24%-64%) reduction in the rate of opioid cessation following surgery. We aimed to identify the underlying factors of the BDI-II (affective/cognitive vs somatic) associated with a decreased rate of opioid cessation after surgery.We conducted a secondary analysis of the data from a previously reported prospective, longitudinal, observational study of opioid use after five distinct surgical procedures (total hip replacement, total knee replacement, thoracotomy, mastectomy, and lumpectomy) in 107 patients. The primary endpoint was time to opioid cessation. After exploratory factor analysis of the BDI-II, mean summary scores were calculated for each identified factor. These scores were evaluated as predictors of time to opioid cessation using Cox proportional hazards regression.The exploratory factor analysis produced three factors (self-loathing symptoms, motivational symptoms, emotional symptoms). All three factors were significant predictors in univariate analysis. Of the three identified factors of the BDI-II, only preoperative self-loathing symptoms (past failure, guilty feelings, self-dislike, self-criticalness, suicidal thoughts, worthlessness) independently predicted a significant decrease in opioid cessation rate after surgery in the multivariate analysis (HR 0.86, 95% CI 0.75-0.99, P value 0.037).Our results identify a set of negative cognitions predicting prolonged time to postoperative opioid cessation. Somatic symptoms captured by the BDI-II were not primarily responsible for the association between preoperative BDI-II scores and postoperative prolonged opioid use.

  View details for DOI 10.1111/pme.12439

  View details for Web of Science ID 000338025900009

  View details for PubMedCentralID PMC4083472

• Outcome of porous tantalum acetabular components for paprosky type 3 and 4 acetabular defects. The Journal of arthroplasty Batuyong, E. D., Brock, H. S., Thiruvengadam, N., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2014; 29 (6): 1318-22

  Abstract

  Porous tantalum acetabular implants provide a potential solution for dealing with significant acetabular bone loss. This study reviews 24 acetabular revisions using tantalum implants for Paprosky type 3 and 4 defects. The mean Harris Hip Score improved from 35±19 (range, 4-71) to 88±14 (range, 41-100), p<0.0001. Postoperative radiographs showed radiolucent lines in 14 hips with a mean width of 1.3±1.0mm (range, 0.27-4.37mm). No gaps enlarged and 71% of them disappeared at a mean of 13±10months (range, 3-29months). At a mean follow-up of 37±14months (range, 24-66months), 22 reconstructions showed radiograpic evidence of osseointegration (92%). The two failures were secondary to septic loosening. When dealing with severe acetabular bone loss, porous tantalum acetabular components show promising short-term results.

  View details for DOI 10.1016/j.arth.2013.12.002

  View details for PubMedID 24405625

• Self-loathing aspects of depression reduce postoperative opioid cessation rate. Pain medicine Hah, J. M., Mackey, S., Barelka, P. L., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F. M., Schmidt, P. C., Carroll, I. R. 2014; 15 (6): 954-964

  Abstract

  We previously reported that increased preoperative Beck Depression Inventory II (BDI-II) scores were associated with a 47% (95% CI 24%-64%) reduction in the rate of opioid cessation following surgery. We aimed to identify the underlying factors of the BDI-II (affective/cognitive vs somatic) associated with a decreased rate of opioid cessation after surgery.We conducted a secondary analysis of the data from a previously reported prospective, longitudinal, observational study of opioid use after five distinct surgical procedures (total hip replacement, total knee replacement, thoracotomy, mastectomy, and lumpectomy) in 107 patients. The primary endpoint was time to opioid cessation. After exploratory factor analysis of the BDI-II, mean summary scores were calculated for each identified factor. These scores were evaluated as predictors of time to opioid cessation using Cox proportional hazards regression.The exploratory factor analysis produced three factors (self-loathing symptoms, motivational symptoms, emotional symptoms). All three factors were significant predictors in univariate analysis. Of the three identified factors of the BDI-II, only preoperative self-loathing symptoms (past failure, guilty feelings, self-dislike, self-criticalness, suicidal thoughts, worthlessness) independently predicted a significant decrease in opioid cessation rate after surgery in the multivariate analysis (HR 0.86, 95% CI 0.75-0.99, P value 0.037).Our results identify a set of negative cognitions predicting prolonged time to postoperative opioid cessation. Somatic symptoms captured by the BDI-II were not primarily responsible for the association between preoperative BDI-II scores and postoperative prolonged opioid use.

  View details for DOI 10.1111/pme.12439

  View details for PubMedID 24964916

• Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement ACTA BIOMATERIALIA Gallo, J., Vaculova, J., Goodman, S. B., Konttinen, Y. T., Thyssen, J. P. 2014; 10 (6): 2354-2366

  Abstract

  Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening/osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. "Control" samples were reported in 45 of the 101 studies. The most frequently examined tissues were the bone-implant interface membrane and pseudosynovial tissues. Histopathological studies contribute importantly to determination of key cell populations underlying the biological mechanisms of aseptic loosening and osteolysis. The studies demonstrated the key molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies.

  View details for DOI 10.1016/j.actbio.2014.02.003

  View details for PubMedID 24525037

• Outcome of Porous Tantalum Acetabular Components for Paprosky Type 3 and 4 Acetabular Defects JOURNAL OF ARTHROPLASTY Batuyong, E. D., Brock, H. S., Thiruvengadam, N., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2014; 29 (6): 1318-1322

  Abstract

  Porous tantalum acetabular implants provide a potential solution for dealing with significant acetabular bone loss. This study reviews 24 acetabular revisions using tantalum implants for Paprosky type 3 and 4 defects. The mean Harris Hip Score improved from 35±19 (range, 4-71) to 88±14 (range, 41-100), p<0.0001. Postoperative radiographs showed radiolucent lines in 14 hips with a mean width of 1.3±1.0mm (range, 0.27-4.37mm). No gaps enlarged and 71% of them disappeared at a mean of 13±10months (range, 3-29months). At a mean follow-up of 37±14months (range, 24-66months), 22 reconstructions showed radiograpic evidence of osseointegration (92%). The two failures were secondary to septic loosening. When dealing with severe acetabular bone loss, porous tantalum acetabular components show promising short-term results.

  View details for DOI 10.1016/j.arth.2013.12.002

  View details for Web of Science ID 000338115400048

• Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. Journal of the Royal Society, Interface / the Royal Society Goodman, S. B., Gibon, E., Pajarinen, J., Lin, T., Keeney, M., Ren, P., Nich, C., Yao, Z., Egashira, K., Yang, F., KONTTINEN, Y. T. 2014; 11 (93): 20130962-?

  Abstract

  Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

  View details for DOI 10.1098/rsif.2013.0962

  View details for PubMedID 24478281

• Fibronectin-aggrecan complex as a marker for cartilage degradation in non-arthritic hips. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA Abrams, G. D., Safran, M. R., Shapiro, L. M., Maloney, W. J., Goodman, S. B., Huddleston, J. I., Bellino, M. J., Scuderi, G. J. 2014; 22 (4): 768-773

  Abstract

  To report hip synovial fluid cytokine concentrations in hips with and without radiographic arthritis.Patients with no arthritis (Tonnis grade 0) and patients with Tonnis grade 2 or greater hip osteoarthritis (OA) were identified from patients undergoing either hip arthroscopy or arthroplasty. Synovial fluid was collected at the time of portal establishment for those undergoing hip arthroscopy and prior to arthrotomy for the arthroplasty group. Analytes included fibronectin-aggrecan complex (FAC) as well as a standard 12 cytokine array. Variables recorded were Tonnis grade, centre-edge angle of Wiberg, as well as labrum and cartilage pathology for the hip arthroscopy cohort. A priori power analysis was conducted, and a Mann-Whitney U test and regression analyses were used with an alpha value of 0.05 set as significant.Thirty-four patients were included (17 arthroplasty, 17 arthroscopy). FAC was the only analyte to show a significant difference between those with and without OA (p < 0.001). FAC had significantly higher concentration in those without radiographic evidence of OA undergoing microfracture versus those not receiving microfracture (p < 0.05).There was a significantly higher FAC concentration in patients without radiographic OA. Additionally, those undergoing microfracture had increased levels of FAC. As FAC is a cartilage breakdown product, no significant amounts may be present in those with OA. In contrast, those undergoing microfracture have focal area(s) of cartilage breakdown. These data suggest that FAC may be useful in predicting cartilage pathology in those patients with hip pain but without radiographic evidence of arthritis.Diagnostic, Level III.

  View details for DOI 10.1007/s00167-014-2863-2

  View details for PubMedID 24477496

• Enhancement of BMP-2 Induced Bone Regeneration by SDF-1a Mediated Stem Cell Recruitment. Tissue engineering. Part A Zwingenberger, S., Yao, Z., Jacobi, A., Vater, C., Valladares, R. D., Li, C., Nich, C., Rao, A. J., Christman, J. E., Antonios, J. K., Gibon, E., Schambach, A., Maetzig, T., Goodman, S. B., Stiehler, M. 2014; 20 (3-4): 810-818

  Abstract

  Treatment of critical size bone defects is challenging. Recent studies showed that the cytokine stromal cell-derived factor 1 alpha (SDF-1α) has potential to improve the bone regenerative effect of low bone morphogenetic protein 2 (BMP-2) concentrations. The goal of this study was to demonstrate the combined effect of SDF-1α and BMP-2 on bone regeneration and stem cell recruitment using a critical size femoral bone defect model. A total of 72 mice were randomized to six groups. External fixators were implanted onto the right femur of each mouse and 3 mm defects were created. Depending on the group affiliation, adenovirally activated fat tissue grafts expressing SDF-1α or/and BMP-2 were implanted at the defect site. One day after operation, 1×10(6) murine mesenchymal stromal cells (MSCs), lentivirally transduced to express the gene enhanced green fluorescent protein (eGFP), firefly luciferase, and CXCR4 were injected systemically in selected groups. Migration of the injected MSCs was observed by bioluminescence imaging on days 0, 2, 4, 6, 8, 10, 12, 14, 21, 28, and 42. After 6 weeks, animals were euthanized and 80 μm CT-scans were performed. For histological investigations, hematoxylin and eosin-, tartrate-resistant acid phosphatase-, alkaline phosphatase-, and anti-eGFP-stained sections were prepared. BMP-2 and SDF-1α combined at the defect site increased bone volume (BV) (2.72 mm(3); 95% CI 1.95-3.49 mm(3)) compared with the negative control group (1.80 mm(3); 95% CI 1.56-2.04 mm(3); p<0.05). In addition, histological analysis confirmed a higher degree of bone healing in the BMP-2 and SDF-1α combined group compared with the negative control group. Bioluminescence imaging demonstrated higher numbers of migrated MSCs toward the defect site in the presence of both BMP-2 and SDF-1α at the defect site. Furthermore, eGFP-labeled migrated MSCs were found in all defect areas, when cells were injected. The ratio of osteoblasts to osteoclasts, assessed by immunohistological staining, was higher and thus showed a trend toward more bone formation for the combined use of BMP-2 and SDF-1α compared with all other groups. This study demonstrated that SDF-1α enhanced BMP-2 mediated bone healing in a critical size segmental bone defect model. Notably, both proteins alone also provided a cumulative effect on MSC attraction toward the site of injury.

  View details for DOI 10.1089/ten.TEA.2013.0222

  View details for PubMedID 24090366

• Editorial Comment: Symposium: 2013 Hip Society Proceedings CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2014; 472 (2): 415–16

  View details for PubMedID 24326592

• Causes of instability after total knee arthroplasty. journal of arthroplasty Song, S. J., Detch, R. C., Maloney, W. J., Goodman, S. B., Huddleston, J. I. 2014; 29 (2): 360-364

  Abstract

  The purpose of the present study was to characterize the underlying causes that lead to instability after total knee arthroplasty (TKA). We reviewed 83 revision TKAs (79 patients) performed for instability. After detailed analysis of patient's history, physical examination, operative report and radiographs, we identified six categories: flexion/extension gap mismatch, component malposition, isolated ligament insufficiency, extensor mechanism insufficiency, component loosening, and global instability. Twenty-five knees presented with multi-factorial instability. When these knees were classified according to the most fundamental category, each category above included 24, 12, 11, 10, 10 and 16 knees respectively. The unstable TKA may result from a variety of distinct etiologies which must be identified and treated at the time of revision. The revision TKA could be tailored to the specific causes.

  View details for DOI 10.1016/j.arth.2013.06.023

  View details for PubMedID 23896358

• High Complication Rate in Revision Total Hip Arthroplasty in Juvenile Idiopathic Arthritis Open Scientific Meeting of the Hip-Society in Conjunction with the Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons (AAOS) Goodman, S. B., Hwang, K., Imrie, S. SPRINGER. 2014: 637–44

  Abstract

  Revision total hip arthroplasty (THA) in patients with juvenile idiopathic arthritis (JIA) is challenging as a result of the patient's young age, systemic disease, multiple affected joints, small proportions, and bone loss. The intermediate- to long-term results of these surgeries remain unknown.The purpose of this study is to determine the (1) functional outcomes; (2) surgical complications; and (3) frequency of reoperation or revision after revision THA for JIA.We reviewed the records of all patients from one center who underwent revision THA for JIA who had a minimum of 5 years of followup (mean, 9 years; range, 5-19 years). This resulted in a series of 24 revision THAs in 15 patients. All patients were Charnley Class C. Age at revision averaged 35 years (range, 21-53 years). The 20 acetabular and 12 femoral revision components included 15 cementless cups, five reconstruction/roof rings with a cemented cup, and four cemented and eight cementless femoral stems.The Harris hip scores improved from 54 (range, 34-85) to 77 (range, 37-100) (p < 0.001). Complications included two proximal femoral fractures associated with severe osteolysis and one sciatic nerve palsy in a patient with severe acetabular deficiency. A total of seven hips (29%) required reoperation or revision surgery, including three for infection (one early and two late) and four for mechanical loosening.Revision THA in JIA is very challenging owing to patients' small proportions and compromised bone stock. The intraoperative and early complication rates are relatively high. Prognosis for long-term survivorship is guarded; limiting factors include periprosthetic osteolysis associated with older implants that used conventional polyethylene and cemented stems.

  View details for DOI 10.1007/s11999-013-3326-7

  View details for PubMedID 24136805

• Innate immunity sensors participating in pathophysiology of joint diseases: a brief overview. Journal of long-term effects of medical implants Gallo, J., Raska, M., Konttinen, Y. T., Nich, C., Goodman, S. B. 2014; 24 (4): 297-317

  Abstract

  The innate immune system consists of functionally specialized "modules" that are activated in response to a particular set of stimuli via sensors located on the surface or inside the tissue cells. These cells screen tissues for a wide range of exogenous and endogenous danger/damage-induced signals with the aim to reject or tolerate them and maintain tissue integrity. In this line of thinking, inflammation evolved as an adaptive tool for restoring tissue homeostasis. A number of diseases are mediated by a maladaptation of the innate immune response, perpetuating chronic inflammation and tissue damage. Here, we review recent evidence on the cross talk between innate immune sensors and development of rheumatoid arthritis, osteoarthritis, and aseptic loosening of total joint replacements. In relation to the latter topic, there is a growing body of evidence that aseptic loosening and periprosthetic osteolysis results from long-term maladaptation of periprosthetic tissues to the presence of by-products continuously released from an artificial joint.

  View details for PubMedID 25747032

• Suppression of NF-?B signaling mitigates polyethylene wear particle-induced inflammatory response. Inflammation and cell signaling Lin, T., Goodman, S. B. 2014; 1 (4)

  Abstract

  In end-stage arthritis patients, total joint replacement is a very effective surgical procedure. Nevertheless, the high revision rate after surgery remains a major concern. The wear particles generated from biomaterial-induced tissue responses may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Several important signaling pathways are involved in wear particles induced inflammatory reactions, including the transcription factor NF-κB. We recently reported that RAW264.7 macrophage cell exposure to ultra-high molecular weight polyethylene (UHMWPE) particles significantly increased the NF-κB activity in a generated NF-κB responsive luciferase reporter cell clone. The NF-κB activity induced by UHMWPE particles in a mouse RAW264.7 macrophage cell line, bone marrow derived macrophages, and human THP1 macrophage cell line, were suppressed by double strand decoy oligodeoxynucleotide (ODN) containing an NF-κB binding element. Macrophages exposure to UHMWPE particles with or without endotoxin induced pro-inflammatory cytokine and chemokine expression including TNF-α, MCP1, MIP1α, and others. Finally, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, consequently reducing macrophage recruitment by cellular conditioned medium exposed to wear particles. These findings suggest that local suppression of inflammatory cytokine production via inhibition of NF-κB activity with decoy ODN in total joint replacement patients could potentially be an effective strategy to alleviate wear particle-induced chronic inflammation.

  View details for PubMedID 26052541

• Case report: Pseudotumor associated with corrosion of a femoral component with a modular neck and a ceramic-on-polyethylene bearing. Journal of long-term effects of medical implants Messana, J., Adelani, M., Goodman, S. B. 2014; 24 (1): 1-5

  Abstract

  Pseudotumor is a rare complication that can occur following hip arthroplasty. This complication may present with pain, swelling, and decreased function and may lead to bone and soft-tissue destruction. We report a case of pseudotumor formation resulting from corrosion of a modular neck in a hip replacement with a ceramic-on-polyethylene bearing. The patient underwent successful revision surgery using an extended trochanteric osteotomy, removal of the entire stem, and implantation of a new femoral stem and ceramic-polyethylene bearing without a modular neck.

  View details for PubMedID 24941400

• Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-?B as a therapeutic target. Acta biomaterialia Lin, T., Tamaki, Y., Pajarinen, J., Waters, H. A., Woo, D. K., Yao, Z., Goodman, S. B. 2014; 10 (1): 1-10

  Abstract

  Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-κB. NF-κB activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1β, IL-6 and MCP1. In addition, NF-κB activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-α or IL-1β) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core IκB/IKKα/β/NF-κB signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-κB activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.

  View details for DOI 10.1016/j.actbio.2013.09.034

  View details for PubMedID 24090989

• Joint replacement surgery and the innate immune system. Journal of long-term effects of medical implants Goodman, S. B., Konttinen, Y. T., Takagi, M. 2014; 24 (4): 253-257

  Abstract

  Total joint replacement is a highly successful, cost-effective surgical procedure that relieves pain and improves function for patients with end-stage arthritis. The most commonly used materials for modern joint replacements include metal alloys such as cobalt chrome and titanium alloys, polymers including polymethylmethacrylate and polyethylene, and ceramics. Implantation of a joint prosthesis incites an acute inflammatory reaction that is regulated by the innate immune system, a preprogrammed non-antigen specific biological response composed of cells, proteins, and other factors. This "frontline" immune mechanism was originally designed to combat invading microorganisms, but now responds to both pathogen-associated molecular patterns or PAMPS (by-products from microorganisms), and damage associated molecular patterns or DAMPS (molecular by-products from cells), via pattern recognition receptors (PRRs). In this way, potentially injurious stimuli that might disrupt the normal homeostatic regulatory mechanisms of the organism are efficiently dealt with, ensuring the survival of the host. Initial surgical implantation of the joint replacement, as well as ongoing generation of wear debris and byproducts during usage of the joint, activates the innate immune system. Understanding and potentially modulating these events may lead to improved function and increased longevity of joint replacements in the future.

  View details for PubMedID 25747028

• Interaction of materials and biology in total joint replacement - successes, challenges and future directions JOURNAL OF MATERIALS CHEMISTRY B Pajarinen, J., Lin, T., Sato, T., Yao, Z., Goodman, S. B. 2014; 2 (41): 7094-7108

  Abstract

  Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function.

  View details for DOI 10.1039/c4tb01005a

  View details for Web of Science ID 000342763700001

  View details for PubMedCentralID PMC4273175

• Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-?B as a therapeutic target. Acta biomaterialia Lin, T., Tamaki, Y., Pajarinen, J., Waters, H. A., Woo, D. K., Yao, Z., Goodman, S. B. 2014; 10 (1): 1-10

  Abstract

  Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-κB. NF-κB activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1β, IL-6 and MCP1. In addition, NF-κB activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-α or IL-1β) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core IκB/IKKα/β/NF-κB signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-κB activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.

  View details for DOI 10.1016/j.actbio.2013.09.034

  View details for PubMedID 24090989

• Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. Journal of the Royal Society, Interface / the Royal Society Goodman, S. B., Gibon, E., Pajarinen, J., Lin, T., Keeney, M., Ren, P., Nich, C., Yao, Z., Egashira, K., Yang, F., KONTTINEN, Y. T. 2014; 11 (93): 20130962-?

  Abstract

  Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

  View details for DOI 10.1098/rsif.2013.0962

  View details for PubMedID 24478281

• Total Knee Arthroplasty in Patients With Juvenile Idiopathic Arthritis CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Heyse, T. J., Ries, M. D., Bellemans, J., Goodman, S. B., Scott, R. D., Wright, T. M., Lipman, J. D., Schwarzkopf, R., Figgie, M. P. 2014; 472 (1): 147-154

  Abstract

  Total knee arthroplasty (TKA) for juvenile idiopathic arthritis is rare but is nonetheless indicated for many patients with this disease. Few reports exist on the results of TKA in patients with juvenile idiopathic arthritis.It was sought to determine (1) survivorship and (2) functional outcomes of TKAs in patients with juvenile idiopathic arthritis.Results were combined from patients treated by experienced surgeons at five hospitals between 1979 and 2011. Two hundred nineteen patients (349 TKAs) were identified and contacted to survey their outcomes at a minimum followup of 2 years (mean, 12 ± 8 years; range, 2-33 years). The average age at surgery was 28.9 ± 9.7 years (range, 11-58 years). Data on revision surgery and ability to perform daily activities were collected.The 10-year survivorship was 95%, decreasing to 82% by 20 years. At latest followup, 31 of 349 TKAs (8.9%) had been revised for either polyethylene failure or loosening (18 TKAs), infection (four), stiffness (three), periprosthetic fractures (two), bilateral amputation for vascular reasons (two), patellar resurfacing (one), and instability (one). Walking tolerance was unlimited in 49%, five to 10 blocks in 23%, and less than five blocks in 28%. Eleven percent could not manage stairs, and another 59% depended on railings. A cane was used by 12% and crutches by 7%; 12% were wheelchair-dependent.TKA survivorship in patients with juvenile idiopathic arthritis was inferior to that typically seen in younger patients with osteoarthritis or even rheumatoid arthritis confirming results of earlier studies with smaller patient numbers. This is especially disconcerting because younger patients require better durability of their TKAs.

  View details for DOI 10.1007/s11999-013-3095-3

  View details for Web of Science ID 000328824400024

  View details for PubMedID 23761173

  View details for PubMedCentralID PMC3889456

• Innate Immune Reactions in Septic and Aseptic Osteolysis around Hip Implants. Journal of long-term effects of medical implants Pajarinen, J., Jamsen, E., Konttinen, Y. T., Goodman, S. B. 2014; 24 (4): 283-296

  Abstract

  According to the long-standing definition, septic and aseptic total joint replacement loosening are two distinct conditions with little in common. Septic joint replacement loosening is driven by bacterial infection whereas aseptic loosening is caused by biomaterial wear debris released from the bearing surfaces. However, recently it has been recognized that the mechanisms that drive macrophage activation in septic and aseptic total joint replacement loosening resemble each other. In particular, accumulating evidence indicates that in addition to mediating bacterial recognition and the subsequent inflammatory reaction, toll-like receptors (TLRs) and their ligands, pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPS), play a key role in wear debris-induced inflammation and macrophage activation. In addition, subclinical bacterial biofilms have been identified from some cases of seemingly aseptic implant loosening. Furthermore, metal ions released from some total joint replacements can activate TLR signaling similar to bacterial derived PAMPs. Likewise, metal ions can function as haptens activating the adaptive immune system similar to bacterial derived antigens. Thus, it appears that aseptic and septic joint replacement loosening share similar underlying pathomechanisms and that this strict dichotomy to sterile aseptic and bacterial-caused septic implant loosening is somewhat questionable. Indeed, rather than being two, well-defined clinical entities, peri-implant osteolysis is, in fact, a spectrum of conditions in which the specific clinical picture is determined by complex interactions of multiple local and systemic factors.

  View details for PubMedID 25747031

• Role of macrophages in the biological reaction to wear debris from joint replacements. Journal of long-term effects of medical implants Nich, C., Goodman, S. B. 2014; 24 (4): 259-265

  Abstract

  Normal usage of total joint replacements results in the production of wear debris and other byproducts. In particular, polyethylene particles are heavily involved in the stimulation of local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone resorption (osteolysis), and, eventually, implant loosening. As sentinels of the innate immune system, cells of the monocyte/macrophage lineage initiate the inflammatory cascade that leads to osteolysis. The biological processes involved are complex, based on the unique properties of the monocytes/macrophages, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The interaction with wear debris triggers the release of pro-inflammatory factors, such as TNF-α, IL-1, and others, pro-osteoclastic factors such as RANKL, and chemokines, such as MCP-1 and MIP-1, all being crucial to the recruitment, migration, differentiation, and ultimately activation of bone resorbing osteoclasts. In parallel, other distinct macrophage populations inhibit inflammation and mitigate its consequences on the bone-implant interface. Here, the role of the monocyte/macrophage cell lineage in the initiation and maintenance of the host inflammatory response to wear debris and subsequent periprosthetic osteolysis is presented.

  View details for PubMedID 25747029

• Macrophage polarization and activation in response to implant debris: influence by "particle disease" and "ion disease". Journal of long-term effects of medical implants Konttinen, Y. T., Pajarinen, J., Takakubo, Y., Gallo, J., Nich, C., Takagi, M., Goodman, S. B. 2014; 24 (4): 267-281

  Abstract

  Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic "eat me" opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14+ monocytes in healthy controls and CD16+ monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit "particle disease" and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni2+, its neighbor in the periodic table Co2+ can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. "Ion disease" concept needs to be incorporated into the "particle disease" concept, due to the toxic, immune, and inflammatory potential of metal ions.

  View details for PubMedID 25747030

• Mutant MCP-1 protein delivery from layer-by-layer coatings on orthopedic implants to modulate inflammatory response. Biomaterials Keeney, M., Waters, H., Barcay, K., Jiang, X., Yao, Z., Pajarinen, J., Egashira, K., Goodman, S. B., Yang, F. 2013; 34 (38): 10287-10295

  Abstract

  Total joint replacement (TJR) is a common and effective surgical procedure for hip or knee joint reconstruction. However, the production of wear particles is inevitable for all TJRs, which activates macrophages and initiates an inflammatory cascade often resulting in bone loss, prosthetic loosening and eventual TJR failure. Macrophage Chemoattractant Protein-1 (MCP-1) is one of the most potent cytokines responsible for macrophage cell recruitment, and previous studies suggest that mutant MCP-1 proteins such as 7ND may be used as a decoy drug to block the receptor and reduce inflammatory cell recruitment. Here we report the development of a biodegradable, layer-by-layer (LBL) coating platform that allows efficient loading and controlled release of 7ND proteins from the surface of orthopedic implants using as few as 14 layers. Scanning electron microscopy and fluorescence imaging confirmed effective coating using the LBL procedure on titanium rods. 7ND protein loading concentration and release kinetics can be modulated by varying the polyelectrolytes of choice, the polymer chemistry, the pH of the polyelectrolyte solution, and the degradation rate of the LBL assembly. The released 7ND from LBL coating retained its bioactivity and effectively reduced macrophage migration towards MCP-1. Finally, the LBL coating remained intact following a femoral rod implantation procedure as determined by immunostaining of the 7ND coating. The LBL platform reported herein may be applied for in situ controlled release of 7ND protein from orthopedic implants, to reduce wear particle-induced inflammatory responses in an effort to prolong the lifetime of implants.

  View details for DOI 10.1016/j.biomaterials.2013.09.028

  View details for PubMedID 24075408

• Macrophage polarization in response to wear particles in vitro CELLULAR & MOLECULAR IMMUNOLOGY Antonios, J. K., Yao, Z., Li, C., Rao, A. J., Goodman, S. B. 2013; 10 (6): 471-482

  Abstract

  Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant (periprosthetic osteolysis). Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory (M1) macrophage phenotype rather than an anti-inflammatory pro-tissue healing (M2) macrophage phenotype. While it has been shown that interleukin-4 (IL-4) selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through IL-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate (PMMA) particles, lipopolysaccharide (LPS) and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M1 phenotype rather than to uncommitted (M0) macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

  View details for DOI 10.1038/cmi.2013.39

  View details for Web of Science ID 000326688400005

  View details for PubMedID 24013843

  View details for PubMedCentralID PMC3818297

• Macrophages-Key cells in the response to wear debris from joint replacements. Journal of biomedical materials research. Part A Nich, C., Takakubo, Y., Pajarinen, J., Ainola, M., Salem, A., Sillat, T., Rao, A. J., Raska, M., Tamaki, Y., Takagi, M., Konttinen, Y. T., Goodman, S. B., Gallo, J. 2013; 101 (10): 3033-3045

  Abstract

  The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening, and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of proinflammatory and pro-osteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34599

  View details for PubMedID 23568608

• Macrophages-Key cells in the response to wear debris from joint replacements JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Nich, C., Takakubo, Y., Pajarinen, J., Ainola, M., Salem, A., Sillat, T., Rao, A. J., Raska, M., Tamaki, Y., Takagi, M., Konttinen, Y. T., Goodman, S. B., Gallo, J. 2013; 101 (10): 3033-3045

  Abstract

  The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening, and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of proinflammatory and pro-osteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34599

  View details for Web of Science ID 000323648300028

• Cause for concern: pseudotumors in patients with hip resurfacing: commentary on an article by R. Bisschop, MD et al.: "High prevalence of pseudotumors in patients with a Birmingham Hip Resurfacing prosthesis: a prospective cohort study of one hundred and twenty-nine patients". The Journal of bone and joint surgery. American volume Goodman, S. B. 2013; 95 (17): e1271–2

  View details for PubMedID 24005211

• Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms ACTA BIOMATERIALIA Gallo, J., Goodman, S. B., KONTTINEN, Y. T., Wimmer, M. A., Holinka, M. 2013; 9 (9): 8046-8058

  Abstract

  Aseptic loosening and other wear-related complications are some of the most frequent late reasons for revision of total knee arthroplasty (TKA). Periprosthetic osteolysis (PPOL) pre-dates aseptic loosening in many cases, indicating the clinical significance of this pathogenic mechanism. A variety of implant-, surgery- and host-related factors have been delineated to explain the development of PPOL. These factors influence the development of PPOL because of changes in mechanical stresses within the vicinity of the prosthetic device, excessive wear of the polyethylene liner, and joint fluid pressure and flow acting on the peri-implant bone. The process of aseptic loosening is initially governed by factors such as implant/limb alignment, device fixation quality and muscle coordination/strength. Later, large numbers of wear particles detached from TKA trigger and perpetuate particle disease, as highlighted by progressive growth of inflammatory/granulomatous tissue around the joint cavity. An increased accumulation of osteoclasts at the bone-implant interface, impairment of osteoblast function, mechanical stresses and increased production of joint fluid contribute to bone resorption and subsequent loosening of the implant. In addition, hypersensitivity and adverse reactions to metal debris may contribute to aseptic TKA failure, but should be determined more precisely. Patient activity level appears to be the most important factor when the long-term development of PPOL is considered. Surgical technique, implant design and material factors are the most important preventative factors, because they influence both the generation of wear debris and excessive mechanical stresses. New generations of bearing surfaces and designs for TKA should carefully address these important issues in extensive preclinical studies. Currently, there is little evidence that PPOL can be prevented by pharmacological intervention.

  View details for DOI 10.1016/j.actbio.2013.05.005

  View details for Web of Science ID 000323402600002

  View details for PubMedID 23669623

  View details for PubMedCentralID PMC4003873

• Development of Poly(ß-amino ester)-Based Biodegradable Nanoparticles for Nonviral Delivery of Minicircle DNA. ACS nano Keeney, M., Ong, S., Padilla, A., Yao, Z., Goodman, S., Wu, J. C., Yang, F. 2013; 7 (8): 7241-7250

  Abstract

  Gene therapy provides a powerful tool for regulating cellular processes and tissue repair. Minicircle (MC) DNA are supercoiled DNA molecules free of bacterial plasmid backbone elements and have been reported to enhance prolonged gene expression compared to conventional plasmids. Despite the great promise of MC DNA for gene therapy, methods for safe and efficient MC DNA delivery remain lacking. To overcome this bottleneck, here we report the development of a poly(β-amino ester) (PBAE)-based, biodegradable nanoparticulate platform for efficient delivery of MC DNA driven by a Ubc promoter in vitro and in vivo. By synthesizing and screening a small library of 18 PBAE polymers with different backbone and end-group chemistry, we identified lead cationic PBAE structures that can complex with minicircle DNA to form nanoparticles, and delivery efficiency can be further modulated by tuning PBAE chemistry. Using human embryonic kidney 293 cells and mouse embryonic fibroblasts as model cell types, we identified a few PBAE polymers that allow efficient MC delivery at levels that are comparable or even surpassing Lipofectamine 2000. The biodegradable nature of PBAE-based nanoparticles facilitates in vivo applications and clinical translation. When injected via intraperitoneal route in vivo, MC alone resulted in high transgene expression, and a lead PBAE/MC nanoparticle formulation achieved a further 2-fold increase in protein expression compared to MC alone. Together, our results highlight the promise of PBAE-based nanoparticles as promising nonviral gene carriers for MC delivery, which may provide a valuable tool for broad applications of MC DNA-based gene therapy.

  View details for DOI 10.1021/nn402657d

  View details for PubMedID 23837668

• Stem cell attraction via SDF-1a expressing fat tissue grafts. Journal of biomedical materials research. Part A Zwingenberger, S., Yao, Z., Jacobi, A., Vater, C., D Valladares, R., Li, C., Nich, C., Rao, A. J., Christman, J. E., Antonios, J. K., Gibon, E., Schambach, A., Mätzig, T., Günther, K., Goodman, S. B., Stiehler, M. 2013; 101 (7): 2067-2074

  Abstract

  Mesenchymal stromal cell (MSCs) are key cellular components for site-specific tissue regeneration. The chemokine stromal derived factor 1 alpha (SDF-1α) is known to attract stem cells via the C-X-C chemokine receptor-4 (CXCR4) receptor. The aim of the study was to develop a model for stem cell attraction using SDF-1α overexpressing fat tissue grafts. Murine MSCs were lentiviral transduced to express the genes for enhanced green fluorescent protein, firefly luciferace, and human CXCR4 (hCXCR4). Murine fat tissue was adenoviral transduced to express SDF-1α and red fluorescent protein transgenes. MSCs were cultured on transwells with SDF-1α containing supernatants from transduced fat tissue. The numbers of migrated MSCs in four groups (with hCXCR4 positive (+) or hCXCR4 negative (-) MSCs with or without SDF-1α containing supernatant) were investigated. After 36 h of culture, 9025 ± 925 cells migrated through the membrane of the transwells in group 1 (CXCR4+/SDF-1α+), 4817 ± 940 cells in group 2 (CXCR4-/SDF-1α+), 2050 ± 766 cells in group 3 (CXCR4+/SDF-1α-), and 2108 ± 426 cells in group 4 (CXCR4-/SDF-1α-). Both, the presence of SDF-1α and the expression of hCXCR4 significantly increased the migration rates (p < 0.0001). MSCs overexpressing the CXCR4 receptor by lentiviral transduction are highly attracted by medium from SDF-1α expressing fat tissue in vitro. Thus, SDF-1α activated tissue grafts may be a strategy to enhance site-specific musculoskeletal tissue regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34512

  View details for PubMedID 23281045

• Direct subcutaneous injection of polyethylene particles over the murine calvaria results in dramatic osteolysis INTERNATIONAL ORTHOPAEDICS Rao, A. J., Zwingenberger, S., Valladares, R., Li, C., Smith, R. L., Goodman, S. B., Nich, C. 2013; 37 (7): 1393-1398

  Abstract

  PURPOSE: The murine calvarial model has been widely employed for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening of total joint replacements. Classically, this model uses an open surgical technique in which polyethylene (PE) particles are directly spread over the calvarium for the induction of osteolysis. We evaluated a minimally invasive modification of the calvarial model by using a direct subcutaneous injection of PE particles. METHODS: Polyethylene (PE) particles were injected subcutaneously over the calvaria of C57BL6J ten-week-old mice ("injection" group) or were implanted after surgical exposure of the calvaria ("open" group) (n = 5/group). For each group, five additional mice received no particles and served as controls. Particle-induced osteolysis was evaluated two weeks after the procedure using high-definition microCT imaging. RESULTS: Polyethylene particle injection over the calvaria resulted in a 40 % ± 1.8 % decrease in the bone volume fraction (BVF), compared to controls. Using the "open surgical technique", the BVF decreased by 16 % ± 3.8 % as compared to controls (p < 0.0001). CONCLUSIONS: Direct subcutaneous injection of PE particles over the murine calvaria produced more profound resorption of bone. Polyethylene particle implantation by injection is less invasive and reliably induces osteolysis to a greater degree than the open technique. This subcutaneous injection method will prove useful for repetitive injections of particles, and the assessment of potential local or systemic therapies.

  View details for DOI 10.1007/s00264-013-1887-4

  View details for Web of Science ID 000320660500028

• Stem cell attraction via SDF-1 expressing fat tissue grafts JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Zwingenberger, S., Yao, Z., Jacobi, A., Vater, C., Valladares, R. D., Li, C., Nich, C., Rao, A. J., Christman, J. E., Antonios, J. K., Gibon, E., Schambach, A., Maetzig, T., Guenther, K., Goodman, S. B., Stiehler, M. 2013; 101A (7): 2067-2074

  Abstract

  Mesenchymal stromal cell (MSCs) are key cellular components for site-specific tissue regeneration. The chemokine stromal derived factor 1 alpha (SDF-1α) is known to attract stem cells via the C-X-C chemokine receptor-4 (CXCR4) receptor. The aim of the study was to develop a model for stem cell attraction using SDF-1α overexpressing fat tissue grafts. Murine MSCs were lentiviral transduced to express the genes for enhanced green fluorescent protein, firefly luciferace, and human CXCR4 (hCXCR4). Murine fat tissue was adenoviral transduced to express SDF-1α and red fluorescent protein transgenes. MSCs were cultured on transwells with SDF-1α containing supernatants from transduced fat tissue. The numbers of migrated MSCs in four groups (with hCXCR4 positive (+) or hCXCR4 negative (-) MSCs with or without SDF-1α containing supernatant) were investigated. After 36 h of culture, 9025 ± 925 cells migrated through the membrane of the transwells in group 1 (CXCR4+/SDF-1α+), 4817 ± 940 cells in group 2 (CXCR4-/SDF-1α+), 2050 ± 766 cells in group 3 (CXCR4+/SDF-1α-), and 2108 ± 426 cells in group 4 (CXCR4-/SDF-1α-). Both, the presence of SDF-1α and the expression of hCXCR4 significantly increased the migration rates (p < 0.0001). MSCs overexpressing the CXCR4 receptor by lentiviral transduction are highly attracted by medium from SDF-1α expressing fat tissue in vitro. Thus, SDF-1α activated tissue grafts may be a strategy to enhance site-specific musculoskeletal tissue regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34512

  View details for Web of Science ID 000319424100025

• Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Rao, A. J., Nich, C., Dhulipala, L. S., Gibon, E., Valladares, R., Zwingenberger, S., Smith, R. L., Goodman, S. B. 2013; 101A (7): 1925-1934

  Abstract

  Wear particles generated with use of total joint replacements incite a chronic macrophage-mediated inflammatory reaction, which leads to implant failure. Macrophage activation may be polarized into two states, with an M1 proinflammatory state dominating an alternatively activated M2 anti-inflammatory state. We hypothesized that IL-4, an activator of M2 macrophages, could modulate polyethylene (PE) particle-induced osteolysis in an experimental murine model. Four animal groups included (a) calvarial saline injection with harvest at 14 days (b) single calvarial injection of PE particles subcutaneously (SC) without IL-4 (c) PE particles placed as in (b), then IL-4 given SC for 14 consecutive days and (d) PE particles as in (b) then IL-4 beginning 7 days after particle injection for 7 days. The calvarial bone volume to total tissue volume was measured using microCT and histomorphometry. Calvaria were cultured for 24 h to assess release of RANKL, OPG, TNF-α, and IL-1ra and isolation and identification of M1 and M2 specific proteins. MicroCT and histomorphometric analysis showed that bone loss was significantly decreased following IL-4 administration to PE treated calvaria for both 7 and 14 days. Western blot analysis showed an increased M1/M2 ratio in the PE treated calvaria, which decreased with addition of IL-4. Cytokine analysis showed that the RANKL/OPG ratio and TNF-α/IL-1ra ratio decreased in PE-treated calvaria following IL-4 addition for 14 days. IL-4 delivery mitigated PE particle-induced osteolysis through macrophage polarization. Modulation of macrophage polarization is a potential treatment strategy for wear particle induced periprosthetic osteolysis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34486

  View details for Web of Science ID 000319424100010

• Direct subcutaneous injection of polyethylene particles over the murine calvaria results in dramatic osteolysis. International orthopaedics Rao, A. J., Zwingenberger, S., Valladares, R., Li, C., Lane Smith, R., Goodman, S. B., Nich, C. 2013; 37 (7): 1393-1398

  Abstract

  PURPOSE: The murine calvarial model has been widely employed for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening of total joint replacements. Classically, this model uses an open surgical technique in which polyethylene (PE) particles are directly spread over the calvarium for the induction of osteolysis. We evaluated a minimally invasive modification of the calvarial model by using a direct subcutaneous injection of PE particles. METHODS: Polyethylene (PE) particles were injected subcutaneously over the calvaria of C57BL6J ten-week-old mice ("injection" group) or were implanted after surgical exposure of the calvaria ("open" group) (n = 5/group). For each group, five additional mice received no particles and served as controls. Particle-induced osteolysis was evaluated two weeks after the procedure using high-definition microCT imaging. RESULTS: Polyethylene particle injection over the calvaria resulted in a 40 % ± 1.8 % decrease in the bone volume fraction (BVF), compared to controls. Using the "open surgical technique", the BVF decreased by 16 % ± 3.8 % as compared to controls (p < 0.0001). CONCLUSIONS: Direct subcutaneous injection of PE particles over the murine calvaria produced more profound resorption of bone. Polyethylene particle implantation by injection is less invasive and reliably induces osteolysis to a greater degree than the open technique. This subcutaneous injection method will prove useful for repetitive injections of particles, and the assessment of potential local or systemic therapies.

  View details for DOI 10.1007/s00264-013-1887-4

  View details for PubMedID 23604215

• Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. Journal of biomedical materials research. Part A Rao, A. J., Nich, C., Dhulipala, L. S., Gibon, E., Valladares, R., Zwingenberger, S., Smith, R. L., Goodman, S. B. 2013; 101 (7): 1926-1934

  Abstract

  Wear particles generated with use of total joint replacements incite a chronic macrophage-mediated inflammatory reaction, which leads to implant failure. Macrophage activation may be polarized into two states, with an M1 proinflammatory state dominating an alternatively activated M2 anti-inflammatory state. We hypothesized that IL-4, an activator of M2 macrophages, could modulate polyethylene (PE) particle-induced osteolysis in an experimental murine model. Four animal groups included (a) calvarial saline injection with harvest at 14 days (b) single calvarial injection of PE particles subcutaneously (SC) without IL-4 (c) PE particles placed as in (b), then IL-4 given SC for 14 consecutive days and (d) PE particles as in (b) then IL-4 beginning 7 days after particle injection for 7 days. The calvarial bone volume to total tissue volume was measured using microCT and histomorphometry. Calvaria were cultured for 24 h to assess release of RANKL, OPG, TNF-α, and IL-1ra and isolation and identification of M1 and M2 specific proteins. MicroCT and histomorphometric analysis showed that bone loss was significantly decreased following IL-4 administration to PE treated calvaria for both 7 and 14 days. Western blot analysis showed an increased M1/M2 ratio in the PE treated calvaria, which decreased with addition of IL-4. Cytokine analysis showed that the RANKL/OPG ratio and TNF-α/IL-1ra ratio decreased in PE-treated calvaria following IL-4 addition for 14 days. IL-4 delivery mitigated PE particle-induced osteolysis through macrophage polarization. Modulation of macrophage polarization is a potential treatment strategy for wear particle induced periprosthetic osteolysis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

  View details for DOI 10.1002/jbm.a.34486

  View details for PubMedID 23225668

• Regional variation in T1? and T2 times in osteoarthritic human menisci: correlation with mechanical properties and matrix composition. Osteoarthritis and cartilage Son, M., Goodman, S. B., Chen, W., Hargreaves, B. A., Gold, G. E., Levenston, M. E. 2013; 21 (6): 796-805

  Abstract

  Changes in T1ρ and T2 magnetic resonance relaxation times have been associated with articular cartilage degeneration, but similar relationships for meniscal tissue have not been extensively investigated. This work examined relationships between T1ρ and T2 measurements and biochemical and mechanical properties across regions of degenerate human menisci.Average T1ρ and T2 relaxation times were determined for nine regions each of seven medial and 13 lateral menisci from 14 total knee replacement patients. Sulfated glycosaminoglycan (sGAG), collagen and water contents were measured for each region. Biomechanical measurements of equilibrium compressive, dynamic compressive and dynamic shear moduli were made for anterior, central and posterior regions.T1ρ and T2 times showed similar regional patterns, with longer relaxation times in the (radially) middle region compared to the inner and outer regions. Pooled over all regions, T1ρ and T2 times showed strong correlations both with one another and with water content. Correlations with biochemical content varied depending on normalization to wet or dry mass, and both imaging parameters showed stronger correlations with collagen compared to sGAG content. Mechanical properties displayed moderate inverse correlations with increasing T1ρ and T2 times and water content.Both T1ρ and T2 relaxation times correlated strongly with water content and moderately with mechanical properties in osteoarthritic menisci, but not as strongly with sGAG or collagen contents alone. While the ability of magnetic resonance imaging (MRI) to detect early osteoarthritic changes remains the subject of investigation, these results suggest that T1ρ and T2 relaxation times have limited ability to detect compositional variations in degenerate menisci.

  View details for DOI 10.1016/j.joca.2013.03.002

  View details for PubMedID 23499673

• Lower Extremity Arthroplasty in Patients With Inflammatory Arthritis: Preoperative and Perioperative Management JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Goodman, S. M., Figgie, M. 2013; 21 (6): 355-363

  Abstract

  Spondylarthritis, which includes conditions such as ankylosing spondylitis and psoriatic arthritis, and rheumatoid arthritis are the most common forms of inflammatory arthritis. Joint inflammation and damage may result in the need for arthroplasty, and the surgeon must be aware of the perioperative challenges associated with these systemic diseases. In patients with inflammatory arthritis who have polyarticular disease and spinal involvement at the time of presentation for lower extremity arthroplasty, preoperative evaluation must include careful evaluation of all joints, including the cervical spine. Preoperative assessment and perioperative management must be appropriate to minimize cardiac and pulmonary complications. Finally, the perioperative management of medications used to manage inflammatory arthritis is critical because these medications may increase the risk of infection and compromise wound healing.

  View details for DOI 10.5435/JAAOS-21-06-355

  View details for Web of Science ID 000209280800006

• Establishment of a femoral critical-size bone defect model in immunodeficient mice JOURNAL OF SURGICAL RESEARCH Zwingenberger, S., Niederlohmann, E., Vater, C., Rammelt, S., Matthys, R., Bernhardt, R., Valladares, R. D., Goodman, S. B., Stiehler, M. 2013; 181 (1): E7-E14

  Abstract

  The development of innovative therapies for bone regeneration requires the use of advanced site-specific bone defect small-animal models. The achievement of proper fixation with a murine model is challenging due to the small dimensions of the murine femur. The aim of this investigation was to find the optimal defect size for a murine critical-size bone defect model using external fixation method.An external fixation device was attached to the right femur of 30 mice. Femoral bone defects of 1 mm (n = 10), 2 mm (n = 10), and 3 mm (n = 10) were created. Wounds were closed without any additional treatment. To investigate bone healing during the 12-wk observation period, x-ray analysis, histomorphology, immunohistochemistry, and μCT scans were performed.MicroCT analyses after 12 wk showed that 3/8 1-mm defects, 5/8 2-mm defects, and 8/8 3-mm defects remained as nonunions. The defect volumes were 0.36 ± 0.42 mm³ (1-mm group), 1.40 ± 0.88 mm³ (2-mm group), and 2.88 ± 0.28 mm³ (3-mm group; P < 0.001, between all groups).Using external fixation, a defect size of 3 mm is necessary to reliably create a persisting femoral bone defect in nude mice.

  View details for DOI 10.1016/j.jss.2012.06.039

  View details for PubMedID 22765996

• The future of biologic coatings for orthopaedic implants BIOMATERIALS Goodman, S. B., Yao, Z., Keeney, M., Yang, F. 2013; 34 (13): 3174-3183

  Abstract

  Implants are widely used for orthopaedic applications such as fixing fractures, repairing non-unions, obtaining a joint arthrodesis, total joint arthroplasty, spinal reconstruction, and soft tissue anchorage. Previously, orthopaedic implants were designed simply as mechanical devices; the biological aspects of the implant were a byproduct of stable internal/external fixation of the device to the surrounding bone or soft tissue. More recently, biologic coatings have been incorporated into orthopaedic implants in order to modulate the surrounding biological environment. This opinion article reviews current and potential future use of biologic coatings for orthopaedic implants to facilitate osseointegration and mitigate possible adverse tissue responses including the foreign body reaction and implant infection. While many of these coatings are still in the preclinical testing stage, bioengineers, material scientists and surgeons continue to explore surface coatings as a means of improving clinical outcome of patients undergoing orthopaedic surgery.

  View details for DOI 10.1016/j.biomaterials.2013.01.074

  View details for PubMedID 23391496

• Cell-based therapies for regenerating bone. Minerva ortopedica e traumatologica : organo ufficiale della Societa piemontese-ligure-lombarda di ortopedia e traumatologia Goodman, S. B. 2013; 64 (2): 107-113

  Abstract

  Cellular therapies to replenish bone lost due to acquired conditions such as trauma, infection, tumor, periprosthetic osteolysis and other etiologies have become widespread. Traditional, open, surgical bone grafting techniques have given way to newer cellular therapies that are potentially less invasive and have a lower complication rate and faster recovery time. These new technologies include bone marrow harvesting with concentration of osteoprogenitor cells with/without cell culture, scaffolds which are both osteoconductive and osteoinductive, attempts to facilitate mesenchymal stem cell and osteoprogenitor cell homing both locally and systemically, genetic engineering of specialized stem cells, and the use of potentially immune-privileged fetal and other types of stem cells. Some of these techniques have already been introduced into the orthopaedic clinic, whereas others are still in the pre-clinical testing phase. Given the limited supply of autologous graft, these new techniques will have a dramatic impact on bone regeneration in the future.

  View details for PubMedID 24436510

  View details for PubMedCentralID PMC3891509

• Cell-based therapies for regenerating bone MINERVA ORTOPEDICA E TRAUMATOLOGICA Goodman, S. B. 2013; 64 (2): 107-113

  Abstract

  Cellular therapies to replenish bone lost due to acquired conditions such as trauma, infection, tumor, periprosthetic osteolysis and other etiologies have become widespread. Traditional, open, surgical bone grafting techniques have given way to newer cellular therapies that are potentially less invasive and have a lower complication rate and faster recovery time. These new technologies include bone marrow harvesting with concentration of osteoprogenitor cells with/without cell culture, scaffolds which are both osteoconductive and osteoinductive, attempts to facilitate mesenchymal stem cell and osteoprogenitor cell homing both locally and systemically, genetic engineering of specialized stem cells, and the use of potentially immune-privileged fetal and other types of stem cells. Some of these techniques have already been introduced into the orthopaedic clinic, whereas others are still in the pre-clinical testing phase. Given the limited supply of autologous graft, these new techniques will have a dramatic impact on bone regeneration in the future.

  View details for Web of Science ID 000320747000002

  View details for PubMedCentralID PMC3891509

• Particle disease: Biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty INNATE IMMUNITY Gallo, J., Goodman, S. B., Konttinen, Y. T., Raska, M. 2013; 19 (2): 213-224

  Abstract

  Numerous studies provide detailed insight into the triggering and amplification mechanisms of the inflammatory response associated with prosthetic wear particles, promoting final dominance of bone resorption over bone formation in multiple bone multicellular units around an implant. In fact, inflammation is a highly regulated process tightly linked to simultaneous stimulation of tissue protective and regenerative mechanisms in order to prevent collateral damage of periprosthetic tissues. A variety of cytokines, chemokines, hormones and specific cell populations, including macrophages, dendritic and stem cells, attempt to balance tissue architecture and minimize inflammation. Based on this fact, we postulate that the local tissue homeostatic mechanisms more effectively regulate the pro-inflammatory/pro-osteolytic cells/pathways in patients with none/mild periprosthetic osteolysis (PPOL) than in patients with severe PPOL. In this line of thinking, 'particle disease theory' can be understood, at least partially, in terms of the failure of local tissue homeostatic mechanisms. As a result, we envision focusing current research on homeostatic mechanisms in addition to traditional efforts to elucidate details of pro-inflammatory/pro-osteolytic pathways. We believe this approach could open new avenues for research and potential therapeutic strategies.

  View details for DOI 10.1177/1753425912451779

  View details for Web of Science ID 000317721600011

  View details for PubMedID 22751380

  View details for PubMedCentralID PMC3712274

• Papers Presented at the Annual Meetings of The Hip Society 2012: Editorial Comment CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2013; 471 (2): 375-376

  View details for DOI 10.1007/s11999-012-2648-1

  View details for Web of Science ID 000313798500007

  View details for PubMedID 23070663

  View details for PubMedCentralID PMC3549189

• Role of direct estrogen receptor signaling in wear particle-induced osteolysis BIOMATERIALS Nich, C., Rao, A. J., Valladares, R. D., Li, C., Christman, J. E., Antonios, J. K., Yao, Z., Zwingenberger, S., Petite, H., Hamadouche, M., Goodman, S. B. 2013; 34 (3): 641-650

  Abstract

  Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate particle-induced osteolysis in the murine calvarial model. Currently, we hypothesize that estrogen receptors (ERs) were involved in this paradoxical phenomenon. To test this hypothesis, we first evaluated polyethylene (PE) particle-induced osteolysis in the murine calvarial model, using wild type (WT) C57BL6J female mice, ERα deficient (ERαKO) mice, and WT mice either treated with 17β-estradiol (E2) or with the ER pan-antagonist ICI 182,780. According to micro-CT and histomorphometry, we showed that bone resorption was consistently altered in both ERαKO and ICI 182,780 treated mice as compared to WT and E2 groups. Then, we demonstrated that ER disruption consistently decreased both PE and polymethylmethacrylate (PMMA) particle-induced production of TNF-α by murine macrophages in vitro. Similar results were obtained following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER disruption and pre treatment with ICI 182,780 resulted in a consistent down-regulation of particle-induced TNF-α mRNA expression relative to WT macrophages or untreated RAW cells. These results indicate that the response to wear particles involves estrogen receptors in female mice, as part of macrophage activation. Estrogen receptors may be considered as a future therapeutic target for particle-induced osteolysis.

  View details for DOI 10.1016/j.biomaterials.2012.10.030

  View details for PubMedID 23113918

• The Cycle of Comorbidities Potential Risks With Delayed Joint Replacement ORTHOPAEDIC NURSING Camillo, P., Thompson, P., Goodman, S. B., Jiang, Y. 2013; 32 (1): 6-13

  Abstract

  Joint replacement is an option that has demonstrated significant improvement in the quality of life for individuals with severe arthritis. However, it is often delayed either in an attempt to avoid future revision surgeries or for other personal reasons. Increasing disability leads to inactivity, chronic pain, and sleep disruption, each of which cycles into significant comorbid risks, many of which are life-threatening. A beginning conceptual framework identified as the cycle of comorbidities is presented to identify these risks and help guide both the patient and the provider in the decision-making process associated with joint replacement surgery.

  View details for DOI 10.1097/NOR.0b013e31827d96be

  View details for PubMedID 23344483

• The basic science of periprosthetic osteolysis. Instructional course lectures Goodman, S. B., Gibon, E., Yao, Z. 2013; 62: 201-206

  Abstract

  Total joint arthroplasty has revolutionized the treatment of arthritic and degenerative conditions for many joints in the body; however, wear debris is continuously generated with day-to-day use of an artificial joint. Excessive production of wear by-products induces a foreign body and chronic inflammatory reaction that accelerates periprosthetic bone destruction and inhibits bone formation. The specific biologic reaction is dependent on the type, amount, and characteristics of the by-products of wear, along with individual genetic variations. For polymeric and ceramic particles, the inflammatory reaction is generally nonspecific and nonimmune; however, with metallic by-products, a type IV, T lymphocyte-mediated, antigen-dependent immune reaction can occur in some patients. The production of proinflammatory cytokines, chemokines, reactive oxygen species, and other mediators is upregulated by wear particles. Animal models have shown that the biologic reaction to wear particles is systemic in nature, not a localized event. Mechanical stimuli and the presence of endotoxin also appear to be important. Efficacious biologic treatments of periprosthetic osteolysis are not yet available. Research continues with the hope that viable strategies for preventing and treating particle-induced osteolysis will be introduced in the future, thus mitigating the need for revision surgery.

  View details for PubMedID 23395025

• Effects of sclerostin antibody on healing of a non-critical size femoral bone defect JOURNAL OF ORTHOPAEDIC RESEARCH Jawad, M. U., Fritton, K. E., Ma, T., Ren, P., Goodman, S. B., Ke, H. Z., Babij, P., Genovese, M. C. 2013; 31 (1): 155-163

  Abstract

  Sclerostin is a glycoprotein secreted by osteocytes and inhibits osteoblastogenesis via inhibition of Wnt signaling. We hypothesized that sclerostin antibody (Scl-AbIII) would accelerate the healing of a murine femoral non-critical size bone defect model. A unilateral and unicortical 0.8 mm-sized drill hole was made in the proximal femoral shaft of adult female nude mice. One group of mice received subcutaneous injections of Scl-AbIII and a second group received vehicle only. Reporter MC3T3 osteoprogenitor cells were injected via the tail vein 3 days after surgery to monitor systemic trafficking of exogenous osteoprogenitors. Bioluminescence imaging (BLI), microcomputed tomography (microCT), micropositron emission tomography (microPET) and histological analysis were used to compare the bone healing responses to Scl-AbIII treatment. Bone mineral density (BMD) significantly increased at the defect site after week 1, and was significantly higher in the treatment compared with the control group at all time points. This finding was also confirmed on histological analysis by increased deposition of new woven bone. MicroPET scanning showed a trend for greater activity in the control group at day 21 compared with the Scl-AbIII group, indicating early bone maturation following treatment with Scl-AbIII. Whereas the BLI signals derived from the injected osteoprogenitor cells showed no differences between vehicle and Scl-AbIII treated groups, systemic migration of MC3T3 cells to the bone defect was clearly identified in both groups using immunohistochemistry. Systemic administration of Scl-AbIII resulted in earlier healing and maturation of a non-critical size bone defect. These findings underscore the potential use of Scl-AbIII for treatment of complicated fractures, non-unions, and other clinical scenarios.

  View details for DOI 10.1002/jor.22186

  View details for PubMedID 22887736

• CORR Insights: Do Patients Lose Weight After Joint Arthroplasty Surgery? A Systematic Review CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2013; 471 (1): 299-300

  Abstract

  This CORR Insights™ is a commentary on the article "Do Patients Lose Weight After Joint Arthroplasty Surgery? A Systematic Review" by Inacio and colleagues available at DOI 10.1007/s11999-012-2537-7 .

  View details for DOI 10.1007/s11999-012-2538-6

  View details for PubMedID 22956234

• Exogenous MC3T3 Preosteoblasts Migrate Systemically and Mitigate the Adverse Effects of Wear Particles TISSUE ENGINEERING PART A Fritton, K., Ren, P., Gibon, E., Rao, A. J., Ma, T., Biswal, S., Gambhir, S. S., Goodman, S. B. 2012; 18 (23-24): 2559-2567

  Abstract

  Understanding how relevant cell types respond to wear particles will reveal new avenues for treating osteolysis following joint replacements. In this study, we investigate the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on preosteoblast migration and function. We infused UHMWPE particles or saline into the left femur of mice and injected luciferase-expressing preosteoblasts (MC3T3 cells) into each left ventricle. Bioluminescence imaging (BLI) confirmed systemic administration of MC3T3 cells. BLI throughout the 28-day experiment showed greater MC3T3 migration to the site of particle infusion than to the site of saline infusion, with significant differences on days 0, 4, and 6 (p≤0.055). Immunostaining revealed a greater number of osteoblasts and osteoclasts in the particle-infused femora, indicating greater bone turnover. The bone mineralization of the particle-infused femora increased significantly when compared to saline-infused femora (an increase of 146.4±27.9 vs. 12.8±8.7 mg/mL, p=0.008). These results show that infused preosteoblasts can migrate to the site of wear particles. Additionally, as the migrated cells were associated with increased bone mineralization in spite of the presence of particles, increasing osteoblast recruitment is a potential strategy for combating bone loss due to increased osteoclast/macrophage number and decreased osteoblast function.

  View details for DOI 10.1089/ten.tea.2012.0086

  View details for PubMedID 22741555

• MI TKA: a risk factor for early revision surgery. The journal of knee surgery Mayle, R. E., Graw, B. P., Huddleston, H. G., Woolson, S. T., Goodman, S. B., Huddleston, J. I. 2012; 25 (5): 423-427

  Abstract

  Minimal incision total knee arthroplasty (MI TKA) was developed with the potential to decrease surgical trauma, pain, and recovery time. While this procedure has increased in popularity, some surgeons have questioned its safety and long-term efficacy. In this study 58 consecutive revision total knee arthroplasties (TKAs) (57 patients) performed at one academic medical center from 2006 to 2008 are reviewed. Prospectively collected clinical and radiographic data included: incision length, gender, age, time to revision surgery, and primary diagnosis at time of revision. Of these, 34 knees involving infection and rerevision were excluded. Of the remaining 24 knees, 11 knees that met inclusion criteria had undergone MI TKA. There were no differences between the groups with regard to age, diagnosis, body mass index, and gender. Average time to revision was shorter for the MI TKA patients (29 vs. 65 months, p < 0.032, odds ratio 14.7). Reasons for revision were aseptic loosening (55%), pain/stiffness (27%), malrotation (9%), and instability (9%) in the MI TKA group and aseptic loosening (53%), instability (15%), pain/stiffness (8%), malrotation (8%), combined malrotation and instability (8%), and polyethylene wear/osteolysis (8%) in the traditional TKA group. These data suggest that MI TKA may be a risk factor for early revision.

  View details for DOI 10.1055/s-0032-1313757

  View details for PubMedID 23150354

• MI TKA: A Risk Factor for Early Revision Surgery JOURNAL OF KNEE SURGERY Mayle, R. E., Graw, B. P., Huddleston, H. G., Woolson, S. T., Goodman, S. B., Huddleston, J. I. 2012; 25 (5): 423-427

  Abstract

  Minimal incision total knee arthroplasty (MI TKA) was developed with the potential to decrease surgical trauma, pain, and recovery time. While this procedure has increased in popularity, some surgeons have questioned its safety and long-term efficacy. In this study 58 consecutive revision total knee arthroplasties (TKAs) (57 patients) performed at one academic medical center from 2006 to 2008 are reviewed. Prospectively collected clinical and radiographic data included: incision length, gender, age, time to revision surgery, and primary diagnosis at time of revision. Of these, 34 knees involving infection and rerevision were excluded. Of the remaining 24 knees, 11 knees that met inclusion criteria had undergone MI TKA. There were no differences between the groups with regard to age, diagnosis, body mass index, and gender. Average time to revision was shorter for the MI TKA patients (29 vs. 65 months, p < 0.032, odds ratio 14.7). Reasons for revision were aseptic loosening (55%), pain/stiffness (27%), malrotation (9%), and instability (9%) in the MI TKA group and aseptic loosening (53%), instability (15%), pain/stiffness (8%), malrotation (8%), combined malrotation and instability (8%), and polyethylene wear/osteolysis (8%) in the traditional TKA group. These data suggest that MI TKA may be a risk factor for early revision.

  View details for DOI 10.1055/s-0032-1313757

  View details for Web of Science ID 000209168300012

• A Pilot Cohort Study of the Determinants of Longitudinal Opioid Use After Surgery ANESTHESIA AND ANALGESIA Carroll, I., Barelka, P., Wang, C. K., Wang, B. M., Gillespie, M. J., McCue, R., Younger, J. W., Trafton, J., Humphreys, K., Goodman, S. B., Dirbas, F., Whyte, R. I., Donington, J. S., Cannon, W. B., Mackey, S. C. 2012; 115 (3): 694-702

  Abstract

  Determinants of the duration of opioid use after surgery have not been reported. We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery.Between January 2007 and April 2009, a prospective, longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain. The primary end point was time to opioid cessation. All analyses were controlled for the type of surgery done.Overall, 6% of patients continued on new opioids 150 days after surgery. Preoperative prescribed opioid use, depressive symptoms, and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use. Preoperative prescribed opioid use was associated with a 73% (95% confidence interval [CI] 0.51%-87%) reduction in the rate of opioid cessation after surgery (P = 0.0009). Additionally, each 1-point increase (on a 4-point scale) of self-perceived risk of addiction was associated with a 53% (95% CI 23%-71%) reduction in the rate of opioid cessation (P = 0.003). Independent of preoperative opioid use and self-perceived risk of addiction, each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42% (95% CI 18%-58%) reduction in the rate of opioid cessation (P = 0.002). The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms than postoperative pain duration or severity.Preoperative factors, including legitimate prescribed opioid use, self-perceived risk of addiction, and depressive symptoms each independently predicted more prolonged opioid use after surgery. Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity.

  View details for DOI 10.1213/ANE.0b013e31825c049f

  View details for PubMedID 22729963

• Advanced Age and Comorbidity Increase the Risk for Adverse Events After Revision Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Koenig, K., Huddleston, J. I., Huddleston, H., Maloney, W. J., Goodman, S. B. 2012; 27 (7): 1402-1407

  Abstract

  With the institution of quality-assurance parameters in health care, physicians must accurately measure and report the true baseline rates of adverse events (AEs) after complex surgical interventions. To better quantify the risk of AEs for revision total hip arthroplasty (THA), we divided a cohort of 306 patients (322 procedures) into age groups: group I (<65 years, n = 138), group II (65-79 years, n = 119), and group III (≥80 years, n = 65). Ninety-day rates of major AE were 9%, 19%, and 34% in the groups, respectively. Group III had an increased chance of experiencing major AE compared with groups I and II. Age and Charlson Comorbidity Index independently predicted major complications, whereas body mass index, sex, and type of revision did not.

  View details for DOI 10.1016/j.arth.2011.11.013

  View details for PubMedID 22245123

• Revision joint replacement, wear particles, and macrophage polarization ACTA BIOMATERIALIA Rao, A. J., Gibon, E., Ma, T., Yao, Z., Smith, R. L., Goodman, S. B. 2012; 8 (7): 2815-2823

  Abstract

  Currently, younger, more active patients are being offered total joint replacement (TJR) for end-stage arthritic disorders. Despite improved durability of TJRs, particle-associated wear of the bearing surfaces continues to be associated with particulate debris, which can activate monocyte/macrophages. Activated macrophages then produce pro-inflammatory factors and cytokines that induce an inflammatory reaction that activates osteoclasts leading to bone breakdown and aseptic loosening. We hypothesized that activated macrophages in tissues harvested from revised joint replacements predominantly express an M1 pro-inflammatory phenotype due to wear-particle-associated cell activation, rather than an M2 anti-inflammatory phenotype. We further questioned whether it is possible to convert uncommitted monocyte/macrophages to an M2 phenotype by the addition of interleukin-4 (IL-4), or whether it is necessary to first pass through an M1 intermediate stage. Retrieved periprosthetic tissues demonstrated increased M1/M2 macrophage ratios compared to non-operated osteoarthritic synovial tissues, using immunohistochemical staining and Western blotting. Uncommitted monocyte/macrophages with/without polymethyl-methacrylate particles were transformed to an M2 phenotype by IL-4 more efficiently when the cells were first passed through an M1 phenotype by exposure to endotoxin. Wear particles induce a pro-inflammatory microenvironment that facilitates osteolysis; these events may potentially be modulated favorably by exposure to IL-4.

  View details for DOI 10.1016/j.actbio.2012.03.042

  View details for PubMedID 22484696

• Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and polyethylene particle-associated bone loss BIOMATERIALS Gibon, E., Yao, Z., Rao, A. J., Zwingenberger, S., Batke, B., Valladares, R., Smith, R. L., Biswal, S., Gambhir, S. S., Goodman, S. B. 2012; 33 (14): 3632-3638

  Abstract

  Particle-associated periprosthetic osteolysis remains a major issue in joint replacement. Ongoing bone loss resulting from wear particle-induced inflammation is accompanied by continued attempts at bone repair. Previously we showed that mesenchymal stem cells (MSCs) are recruited systemically to bone exposed to continuous infusion of ultra high molecular weight polyethylene (UHMWPE) particles. The chemokine-receptor axis that mediates this process is unknown. We tested two hypotheses: (1) the CCR1 receptor mediates the systemic recruitment of MSCs to UHMWPE particles and (2) recruited MSCs are able to differentiate into functional mature osteoblasts and decrease particle-associated bone loss. Nude mice were allocated randomly to four groups. UHMWPE particles were continuously infused into the femoral shaft using a micro-pump. Genetically modified murine wild type reporter MSCs were injected systemically via the left ventricle. Non-invasive imaging was used to assay MSC migration and bone mineral density. Bioluminescence and immunohistochemistry confirmed the chemotaxis of reporter cells and their differentiation into mature osteoblasts in the presence of infused particles. Injection of a CCR1 antagonist decreased reporter cell recruitment to the UHMWPE particle infusion site and increased osteolysis. CCR1 appears to be a critical receptor for chemotaxis of MSCs in the presence of UHMWPE particles. Interference with CCR1 exacerbates particle-induced bone loss.

  View details for DOI 10.1016/j.biomaterials.2012.02.003

  View details for PubMedID 22364730

• Macrophage polarization: An opportunity for improved outcomes in and regenerative medicine BIOMATERIALS Brown, B. N., Ratner, B. D., Goodman, S. B., Amar, S., Badylak, S. F. 2012; 33 (15): 3792-3802

  Abstract

  The host response to biomaterials has been studied for decades. Largely, the interaction of host immune cells, macrophages in particular, with implanted materials has been considered to be a precursor to granulation tissue formation, the classic foreign body reaction, and eventual encapsulation with associated negative impacts upon device functionality. However, more recently, it has been shown that macrophages, depending upon context dependent polarization profiles, are capable of affecting both detrimental and beneficial outcomes in a number of disease processes and in tissue remodeling following injury. Herein, the diverse roles played by macrophages in these processes are discussed in addition to the potential manipulation of macrophage effector mechanisms as a strategy for promoting site-appropriate and constructive tissue remodeling as opposed to deleterious persistent inflammation and scar tissue formation.

  View details for DOI 10.1016/j.biomaterials.2012.02.034

  View details for Web of Science ID 000303273200002

  View details for PubMedID 22386919

• MC3T3-E1 Osteoprogenitor Cells Systemically Migrate to a Bone Defect and Enhance Bone Healing TISSUE ENGINEERING PART A Gibon, E., Batke, B., Jawad, M. U., Fritton, K., Rao, A., Yao, Z., Biswal, S., Gambhir, S. S., Goodman, S. B. 2012; 18 (9-10): 968-973

  Abstract

  Although iliac crest autologous bone graft remains the gold standard for treatment of bone defects, delayed- and nonunions, and arthrodeses, several alternative strategies have been attempted, including the use of mesenchymal stem cells. Whether cells from the osteoblast lineage demonstrate systemic recruitment to an acute bone defect or fracture, and whether these cells directly participate in bone healing is controversial. This study tests two hypotheses: (1) that exogenous murine MC3T3-E1 osteoprogenitor cells with a high propensity for osteoblast differentiation are able to systemically migrate to a bone defect and (2) that the migrated MC3T3-E1 cells enhance bone healing. Two groups of nude mice were used; a bone defect was drilled in the left femoral shaft in both groups. MC3T3-E1 were used as reporter cells and injected in the left ventricle of the heart, to avoid sequestration in the lungs. Injection of saline served as a control. We used bioluminescence and microCT to assay cell recruitment and bone mineral density (BMD). Immunohistochemical staining was used to confirm the migration of reporter cells. MC3T3-E1 cells were found to systemically migrate to the bone defect. Further, BMD at the defect was significantly increased when cells were injected. Systemic cell therapy using osteoprogenitor cells may be a potential strategy to enhance bone healing.

  View details for DOI 10.1089/ten.tea.2011.0545

  View details for PubMedID 22129134

• American Academy of Orthopaedic Surgeons clinical practice guideline on: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. journal of bone and joint surgery. American volume Jacobs, J. J., Mont, M. A., Bozic, K. J., Della Valle, C. J., Goodman, S. B., Lewis, C. G., Yates, A. C., Boggio, L. N., Watters, W. C., Turkelson, C. M., Wies, J. L., Sluka, P., Hitchcock, K. 2012; 94 (8): 746-747

  View details for DOI 10.2106/JBJS.9408.ebo746

  View details for PubMedID 22517391

  View details for PubMedCentralID PMC3326685

• Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles JOURNAL OF ORTHOPAEDIC RESEARCH Gibon, E., Ma, T., Ren, P., Fritton, K., Biswal, S., Yao, Z., Smith, L., Goodman, S. B. 2012; 30 (4): 547-553

  Abstract

  The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of ultra high molecular weight polyethylene (UHMWPE) particles. Six groups of nude mice were used. We used non-invasive imaging to assay macrophage recruitment and osteolysis. A murine macrophage cell line and primary wild type and CCR2 knockout murine macrophages were used as the reporter cells. Particles were infused into the femoral canal. Bioluminescence and immunohistochemical staining were used to confirm the migration of reporter cells. Locally infused MCP-1 induced systemic macrophage trafficking to bone. Injection of MCP-1 receptor antagonist significantly decreased reporter cell recruitment to bone infused with UHMWPE particles and decreased osteolysis. Systemic migration of reporter cells to infused particles was decreased when the reporter cells were deficient in the CCR2 receptor. Interruption of the MCP-1 ligand-receptor axis appears to be a viable strategy to mitigate trafficking of macrophages and osteolysis due to UHMWPE particles.

  View details for DOI 10.1002/jor.21548

  View details for PubMedID 21913218

• Cancellous Impaction Bone Grafting of Acetabular Defects in Complex Primary and Revision Total Hip Arthroplasty ORTHOPEDICS Patil, N., Hwang, K., Goodman, S. B. 2012; 35 (3): E306-E312

  Abstract

  The reconstruction of major acetabular bone defects during revision, conversion, and primary total hip arthroplasties (THAs) is challenging. We reviewed a consecutive series of 168 THAs (108 revisions, 8 conversions, and 52 primary THAs) performed by 1 surgeon (S.B.G.) between 1997 and 2008 using impaction bone grafting for acetabular reconstruction. Autograft, cancellous allograft croutons, and demineralized bone matrix were used to fill bone defects as needed. The acetabular bone deficiency was classified according to the American Academy of Orthopaedic Surgeons: type I, segmental deficiency with significant rim defect; type II, cavitary defects medially or posteriorly; type III, combined cavitary and segmental deficiency; type IV, pelvic discontinuity; and type V, arthrodesis. According to this method, 56 hips had type I, 31 hips had type II, 48 hips had type III, and 27 hips had type IV deficiencies. Of the 168 patients, 19 subsequently died of causes unrelated to the THA, and 11 were lost to follow-up. All patients had at least 2 years of follow-up. Average Harris Hip Score improved from 45.5±17.9 preoperatively to 81.1±16.5 postoperatively (P<.05) for revision THAs, from 40.0±11.3 preoperatively to 85.0±12.8 postoperatively (P<.05) for conversion THAs, and from 42.3±14.9 preoperatively to 85.0±12.0 postoperatively (P<.05) for primary THAs. All impaction grafted bone (allograft, autograft, or a combination) incorporated radiographically, thus restoring bone stock. Complications included 1 early infection, which was managed successfully with debridement and liner exchange, and 2 late infections that were managed successfully with staged revision. Two revisions required subsequent re-revision for late loosening. Two hip dislocations occurred, 1 of which required surgical treatment to place a constrained liner.

  View details for DOI 10.3928/01477447-20120222-24

  View details for Web of Science ID 000301501500002

  View details for PubMedID 22385438

• Context and Consequences of Delaying Hip Replacement Surgery: A Case Study JNP-JOURNAL FOR NURSE PRACTITIONERS Camillo, P., Goodman, S. B., Thompson, P., Imrie, S. N. 2012; 8 (3): 212-?

  View details for DOI 10.1016/j.nurpra.2011.07.029

  View details for Web of Science ID 000209401900008

• Papers Presented at the Annual Meetings of the Hip Society 2011 CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2012; 470 (2): 327-328

  View details for DOI 10.1007/s11999-011-2122-5

  View details for Web of Science ID 000299056000001

  View details for PubMedID 22002825

  View details for PubMedCentralID PMC3254752

• Unexpected failure of highly cross-linked polyethylene acetabular liner. journal of arthroplasty Waewsawangwong, W., Goodman, S. B. 2012; 27 (2): 323 e1-4

  Abstract

  Highly cross-linked polyethylene (HXPE) in total hip arthroplasty has been shown to decrease wear rate compared with conventional liner. However, it has some disadvantages in that the mechanical properties cause early failure of the implant. This case report presents an unexpected failure of total hip arthroplasty in a 72-year-old woman that occurred at 20 months postsurgery. Operative findings revealed fracture of superior rim at locking groove of liner. We concluded that the failure was caused by decreased mechanical properties of highly cross-linked polyethylene, less thickness of polyethylene, more vertical cup, and use of large femoral head.

  View details for DOI 10.1016/j.arth.2011.04.010

  View details for PubMedID 21601415

• Recommendations and Considerations for the Use of Biologics in Orthopedic Surgery BIODRUGS Zwingenberger, S., Nich, C., Valladares, R. D., Yao, Z., Stiehler, M., Goodman, S. B. 2012; 26 (4): 245-256

  Abstract

  Reconstruction of extensive bone defects remains technically challenging and has considerable medical and financial impact on our society. Surgical procedures often require a bone/substitute graft to enhance and accelerate bone repair. Bone autografts are associated with morbidity related to bone harvesting and are limited in quantity. Alternatively, bone allografts expose the patient to the risk of transmission of infectious disease. Synthetic bone graft substitutes, such as calcium sulfates, hydroxyapatite, tricalcium phosphate, and combinations, circumvent some of the disadvantages of auto- and allografts, but have limited indications. Biomedical research has made possible the stimulation of the body's own healing mechanisms, either by delivering exogenous growth factors locally, or by stimulating their local production by gene transfer. Among all known factors having osteoinductive properties, only two bone morphogenetic proteins (for specific indications) and demineralized bone matrix have been approved for clinical use. In addition, ongoing research is exploring the efficacy of cell therapy and tissue engineering. The present report examines the composition, biological properties, indications, clinical experience and regulations of several of the biotherapeutics employed for bone reconstruction.

  View details for PubMedID 22671767

• Advantages and disadvantages of ceramic on ceramic total hip arthroplasty: A review BIOMEDICAL PAPERS-OLOMOUC Gallo, J., Goodman, S. B., Lostak, J., Janout, M. 2012; 156 (3): 204-212

  Abstract

  Ceramic on ceramic (COC) total hip arthroplasty (THA) was developed to reduce wear debris and accordingly, the occurrence of osteolysis and aseptic loosening especially in younger patients. Based on the excellent tribological behavior of current COC bearings and the relatively low biological activity of ceramic particles, significant improvement in survivorship of these implants is expected.We used manual search to identify all relevant studies reporting clinical data on COC THAs in PubMed. The objective was to determine whether current COC THA offers a better clinical outcome and survivorship than non-COC THA.Studies with early generation ceramic bearings yielded 68% to 84% mean survivorship at 20 years follow-up which is comparable with the survivorship of non-COC THAs. Studies on current ceramic bearings report a 10-year revision-free interval of 92% to 99%. These outcomes are comparable to the survivorship of the best non-COC THAs. However, there are still concerns regarding fracture of sandwich ceramic liners, squeaking, and impingement of the femoral neck on the rim of the ceramic liner leading to chipping, especially in younger and physically active patients.Current COC THA leads to equivalent but not improved survivorship at 10 years follow-up in comparison to the best non-COC THA. Based on this review, we recommend that surgeons weigh the potential advantages and disadvantages of current COC THA in comparison to other bearing surfaces when considering young very active patients who are candidates for THA.

  View details for DOI 10.5507/bp.2012.063

  View details for Web of Science ID 000310725900003

  View details for PubMedID 23069885

• Successful closed reduction of a dislocated constrained total hip arthroplasty: a case report and literature review. The open orthopaedics journal Sonohata, M., Waewsawangwong, W., Goodman, S. B. 2012; 6: 211-214

  Abstract

  Many surgeons use acetabular components with constrained polyethylene liners to improve stability after total hip arthroplasty in patients with a history of hip dislocation. Surgical treatment is generally thought to be the only available option for the dislocated constrained liner. The success rate and clinical results of closed reduction for such patients is unclear. This report presents a case of a successful closed reduction of a dislocated constrained liner. Few papers have so far addressed closed reduction of a dislocated constrained liner. Furthermore, previous studies reported a variety of components. Publication of additional successful and unsuccessful case reports is therefore needed to help establish the optimal treatment protocol for a dislocated constrained liner.

  View details for DOI 10.2174/1874325001206010211

  View details for PubMedID 22675412

• Prospective, Randomized Study Between Insall-Burstein II and NexGen Legacy with a Minimum 9-Year Follow-Up JOURNAL OF ARTHROPLASTY Oh, K., Goodman, S. B., Yang, J. 2011; 26 (8): 1232-1238

  Abstract

  A randomized, prospective, comparative study was performed in 2 related, adjacent generation posterior stabilized total knee prostheses, to evaluate whether the newer design improved the clinical and radiographic outcome for treatment of advanced osteoarthritis of the knee. Ninety one total knee arthroplasties in 84 patients (45 Insall-Burstein II and 46 NexGen Legacy posterior stabilized [both from Zimmer, Warsaw, Ind] prostheses) with an average of 10.3 years of follow-up (range, 9-11.8 years) were included. The preoperative diagnoses were primary osteoarthritis in all patients. At the latest evaluation, there were no significant differences detected in the mean clinical and functional knee scores, average postoperative active range of motion, and anterior knee pain between the Insall-Burstein II and the NexGen Legacy groups postoperatively.

  View details for DOI 10.1016/j.arth.2010.12.018

  View details for Web of Science ID 000297389100020

  View details for PubMedID 21295941

• Outcome of Primary Total Hip Arthroplasty in Charnley Class C Patients with Juvenile Idiopathic Arthritis A Case Series JOURNAL OF ARTHROPLASTY De Ranieri, A., Wagner, N., Imrie, S. N., Hwang, K. L., Goodman, S. B. 2011; 26 (8): 1182-1188

  Abstract

  The outcome and complications of 37 primary total hip arthroplasties by one surgeon in 24 patients with Charnley Class C juvenile idiopathic arthritis with up to 19.6 years follow-up are reported. Twenty-six femoral components were cementless; all acetabular components were cementless with screws. Age at operation averaged 22.6 years. Two patients (3 hips) have died. Twelve hips in 9 patients have failed. Six cementless acetabular components with conventional polyethylene were revised because of osteolysis after 5.5 to 14.5 years. All 3 cementless C2 femoral stems with minimal porous coating failed. One of eight cemented AML Bantam stems loosened at 3.5 years; 2 of 23 cementless AML Bantam stems loosened at 9.5 and 19.6 years. Pain relief and functional improvement are dramatic after total hip arthroplasty in juvenile idiopathic arthritis; however, the long-term outcome is guarded.

  View details for DOI 10.1016/j.arth.2010.10.003

  View details for PubMedID 21167675

• Preventing Venous Thromboembolic Disease in Patients Undergoing Elective Hip and Knee Arthroplasty JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Mont, M. A., Jacobs, J. J., Boggio, L. N., Bozic, K. J., Della Valle, C. J., Goodman, S. B., Lewis, C. G., Yates, A. J., Watters, W. C., Turkelson, C. M., Wies, J. L., Donnelly, P., Patel, N., Sluka, P. 2011; 19 (12): 768-776

  Abstract

  This guideline supersedes a prior one from 2007 on a similar topic. The work group evaluated the available literature concerning various aspects of patient screening, risk factor assessment, and prophylactic treatment against venous thromboembolic disease (VTED), as well as the use of postoperative mobilization, neuraxial agents, and vena cava filters. The group recommended further assessment of patients who have had a previous venous thromboembolism but not for other potential risk factors. Patients should be assessed for known bleeding disorders, such as hemophilia, and for the presence of active liver disease. Patients who are not at elevated risk of VTED or for bleeding should receive pharmacologic prophylaxis and mechanical compressive devices for the prevention of VTED. The group did not recommend specific pharmacologic agents and/or mechanical devices. The work group recommends, by consensus opinion, early mobilization for patients following elective hip and knee arthroplasty. The use of neuraxial anesthesia can help limit blood loss but was not found to affect the occurrence of VTED. No clear evidence was established regarding whether inferior vena cava filters can prevent pulmonary embolism in patients who have a contraindication to chemoprophylaxis and/or known VTED.

  View details for Web of Science ID 000297563900007

  View details for PubMedID 22134209

• Identification of a central role for complement in osteoarthritis NATURE MEDICINE Wang, Q., Rozelle, A. L., Lepus, C. M., Scanzello, C. R., Song, J. J., Larsen, D. M., Crish, J. F., Bebek, G., Ritter, S. Y., Lindstrom, T. M., Hwang, I., Wong, H. H., Punzi, L., Encarnacion, A., Shamloo, M., Goodman, S. B., Wyss-Coray, T., Goldring, S. R., Banda, N. K., Thurman, J. M., Gobezie, R., Crow, M. K., Holers, V. M., Lee, D. M., Robinson, W. H. 2011; 17 (12): 1674-U196

  Abstract

  Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.

  View details for DOI 10.1038/nm.2543

  View details for Web of Science ID 000297978000042

  View details for PubMedID 22057346

  View details for PubMedCentralID PMC3257059

• Molecular profile of osteoprogenitor cells seeded on allograft bone JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE Smith, K. E., Huang, Z., Ma, T., Irani, A., Smith, R. L., Goodman, S. B. 2011; 5 (9): 704-711

  Abstract

  In order to optimize and modulate bone formation it is essential to understand the expression patterns of key bone-specific growth factors, as osteoprogenitor cells undergo the processes of proliferation, differentiation and maturation. This study reports the sequential expression of bone-related growth and transcription factors when bone marrow-derived osteoprogenitor cells from C57BL mice were cultured on allograft bone discs. Mineralization and osteocalcin protein levels were used to track osteogenic differentiation and maturation. Bone-related growth factors, such as Bmp-2, Bmp-7, Ctnnb-1, Fgf-2, Igf-1, Vegf-a and Tgf-β1, and transcription factors, such as Runx-2 and osteocalcin, were examined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Total density of mineralized bone was significantly increased 7.6 ± 0.7% in allografts cultured with cells, compared with a 0.5 ± 2.0% increase in the controls without cells (p < 0.01). Osteocalcin protein levels peaked at day 4. Protein expression showed peaks of BMP-2 and TGF-β1 on day 2, with VEGF peaking on day 8, and IGF-1 decreasing on day 2. mRNA for Pdgf-a peaked on day 2; Bmp-2 on days 4 and 16; Ctnnb-1 on days 8 and 20; Vegf-a, Fgf-2, Runx-2 and Igf-1 on day 12; Tgf-β1 on day 16; and Pdgf-b on day 20. Osteogenic growth factors correlated with Runx-2 and Ctnnb-1, whereas a predominant vascular growth factor, Vegf-a, did not follow this pattern. Specific bone-related genes and proteins were expressed in a time-dependent manner when osteoprogenitor cells were cultured on cortico-cancellous bone discs in vitro.

  View details for DOI 10.1002/term.367

  View details for PubMedID 21953868

• Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis JOURNAL OF CLINICAL INVESTIGATION Song, J. J., Hwang, I., Cho, K. H., Garcia, M. A., Kim, A. J., Wang, T. H., Lindstrom, T. M., Lee, A. T., Nishimura, T., Zhao, L., Morser, J., Nesheim, M., Goodman, S. B., Lee, D. M., Bridges, S. L., Gregersen, P. K., Leung, L. L., Robinson, W. H. 2011; 121 (9): 3517-3527

  Abstract

  The immune and coagulation systems are both implicated in the pathogenesis of rheumatoid arthritis (RA). Plasma carboxypeptidase B (CPB), which is activated by the thrombin/thrombomodulin complex, plays a procoagulant role during fibrin clot formation. However, an antiinflammatory role for CPB is suggested by the recent observation that CPB can cleave proinflammatory mediators, such as C5a, bradykinin, and osteopontin. Here, we show that CPB plays a central role in downregulating C5a-mediated inflammatory responses in autoimmune arthritis. CPB deficiency exacerbated inflammatory arthritis in a mouse model of RA, and cleavage of C5a by CPB suppressed the ability of C5a to recruit immune cells in vivo. In human patients with RA, genotyping of nonsynonymous SNPs in the CPB-encoding gene revealed that the allele encoding a CPB variant with longer half-life was associated with a lower risk of developing radiographically severe RA. Functionally, this CPB variant was more effective at abrogating the proinflammatory properties of C5a. Additionally, expression of both CPB and C5a in synovial fluid was higher in patients with RA than in those with osteoarthritis. These findings suggest that CPB plays a critical role in dampening local, C5a-mediated inflammation and represents a molecular link between inflammation and coagulation in autoimmune arthritis.

  View details for DOI 10.1172/JCI46387

  View details for PubMedID 21804193

• Role of the Toll-like receptor pathway in the recognition of orthopedic implant wear-debris particles BIOMATERIALS Pearl, J. I., Ma, T., Irani, A. R., Huang, Z., Robinson, W. H., Smith, R. L., Goodman, S. B. 2011; 32 (24): 5535-5542

  Abstract

  The inflammatory response to prosthetic implant-derived wear particles is the primary cause of bone loss and aseptic loosening of implants, but the mechanisms by which macrophages recognize and respond to particles remain unknown. Studies of innate immunity demonstrate that Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPS). All TLRs signal through myeloid differentiation factor 88 (MyD88), except TLR3 which signals through TIR domain containing adapter inducing interferon-beta (TRIF), and TLR4 which signals through both MyD88 and TRIF. We hypothesized that wear-debris particles may act as PAMPs/DAMPs and activate macrophages via TLRs. To test this hypothesis, we first demonstrated that inhibition of MyD88 decreases polymethylmethacrylate (PMMA) particle-induced production of TNF-α in RAW 264.7 macrophages. Next we compared particle-induced production of TNF-α among MyD88 knockout (MyD88(-/-)), TRIF knockout (TRIF(-/-)), and wild type (WT) murine macrophages. Relative to WT, disruption of MyD88 signaling diminished, and disruption of TRIF amplified the particle-induced production of TNF-α. Gene expression data indicated that this latter increase in TNF-α was due to a compensatory increase in expression of MyD88 associated components of the TLR pathway. Finally, using an in vivo model, MyD88(-/-) mice developed less particle-induced osteolysis than WT mice. These results indicate that the response to PMMA particles is partly dependent on MyD88, presumably as part of TLR signaling; MyD88 may represent a therapeutic target for prevention of wear debris-induced periprosthetic osteolysis.

  View details for DOI 10.1016/j.biomaterials.2011.04.046

  View details for PubMedID 21592562

• Toll-Like Receptors and Their Adaptors are Regulated in Macrophages after Phagocytosis of Lipopolysaccharide-Coated Titanium Particles JOURNAL OF ORTHOPAEDIC RESEARCH Hirayama, T., Tamaki, Y., Takakubo, Y., Iwazaki, K., Sasaki, K., Ogino, T., Goodman, S. B., Konttinen, Y. T., Takagi, M. 2011; 29 (7): 984-992

  Abstract

  Macrophages phagocytose metallic wear particles and produce mediators, which can induce cellular host response and aseptic implant loosening. Lipopolysaccharide (LPS) on the wear debris can stimulate macrophages via Toll-like receptor 4 (TLR4) and enhance the response. However, the precise functional role and interaction of TLRs and their adaptor molecules is still unclear. Rat bone marrow macrophages were stimulated with titanium particle (Ti) coated by LPS (Ti/LPS+) and LPS-free Ti (Ti/LPS-). mRNA levels of cytokines, TLRs and their adaptor molecules were measured using real time PCR. mRNA levels of TNF-α, IL-1β, and IL-6 increased in Ti/LPS+ than Ti/LPS-. In contrast, mRNA levels of TLR4, TLR5, and TLR9 decreased in Ti/LPS+ compared to Ti/LPS-. mRNA levels of MyD88, IRAK1, IRAK4 decreased gradually, and TRAF6 underwent an initial transient increase, followed by suppression in Ti/LPS+. However, mRNA levels of TLR2 and IRAK2 increased after phagocytosis of Ti/LPS+ than Ti/LPS-. The increased expressions of proinflammatory cytokines found in Ti/LPS+ indicated that their productions cytokines could be enhanced by phagocytosis of LPS-coated particles. Subsequent down-regulation of TLR4, TLR5, TLR9, MyD88, IRAK1, and IRAK4 suggests that self-protective mechanisms to regulate excessive host responses are activated in macrophages. Increase of TLR2 and IRAK2 and a transient increase of TRAF6 in Ti/LPS+ suggest that another possible pathway to modulate TLR-mediated cellular response to prolong inflammatory response in foreign body reaction of aseptic loosening. This down- and/or up-regulation of the potential TLR-mediated responses to LPS-coated particles reflects the proactive behavior of effector cells.

  View details for DOI 10.1002/jor.21369

  View details for Web of Science ID 000290632900003

  View details for PubMedID 21308757

• New MR Imaging Methods for Metallic Implants in the Knee: Artifact Correction and Clinical Impact JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, C. A., Chen, W., Goodman, S. B., Hargreaves, B. A., Koch, K. M., Lu, W., Brau, A. C., Draper, C. E., Delp, S. L., Gold, G. E. 2011; 33 (5): 1121-1127

  Abstract

  To evaluate two magnetic resonance imaging (MRI) techniques, slice encoding for metal artifact correction (SEMAC) and multiacquisition variable-resonance image combination (MAVRIC), for their ability to correct for artifacts in postoperative knees with metal.A total of 25 knees were imaged in this study. Fourteen total knee replacements (TKRs) in volunteers were scanned with SEMAC, MAVRIC, and 2D fast spin-echo (FSE) to measure artifact extent and implant rotation. The ability of the sequences to measure implant rotation and dimensions was compared in a TKR knee model. Eleven patients with a variety of metallic hardware were imaged with SEMAC and FSE to compare artifact extent and subsequent patient management was recorded.SEMAC and MAVRIC significantly reduced artifact extent compared to FSE (P < 0.0001) and were similar to each other (P = 0.58), allowing accurate measurement of implant dimensions and rotation. The TKRs were properly aligned in the volunteers. Clinical imaging with SEMAC in symptomatic knees significantly reduced artifact (P < 0.05) and showed findings that were on the majority confirmed by subsequent noninvasive or invasive patient studies.SEMAC and MAVRIC correct for metal artifact, noninvasively providing high-resolution images with superb bone and soft tissue contrast.

  View details for DOI 10.1002/jmri.22534

  View details for PubMedID 21509870

• Anesthesia and Rheumatoid Arthritis REVISTA BRASILEIRA DE ANESTESIOLOGIA Vieira, E. M., Goodman, S., Tanaka, P. P. 2011; 61 (3): 367-375

  Abstract

  Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology. It is known that RA patients have a reduced life expectancy when compared with the general population. Rheumatic diseases are numerous and occur with high variability; some of them develop very rapidly while others occur chronically provoking disability throughout life. Anesthetic risks in osteoarticular disorders involve not only the mechanical deformations caused by the disease, but also the cardiovascular, respiratory, renal, and digestive systems.The purpose of this review was to stress the importance of stages in disease process that may affect anesthesia control before, during, and after surgery, highlighting the authors' experience in a retrospective review of patients with juvenile rheumatoid arthritis (JRA) undergoing placement of orthopedic prosthesis with emphasis on intubation techniques.Rheumatoid arthritis patients can present a number of complex problems for the anesthesiologist. This requires careful preoperative evaluation; anesthesia requires experience with the technique; and postoperative care should be judiciously chosen to meet the specific needs of the patient. The procedure requires effective communication among surgeon, rheumatologist and anesthesiologist so each member of the multidisciplinary team can contribute with his/her expertise in order to better benefit the patient.

  View details for Web of Science ID 000290844000013

  View details for PubMedID 21596198

• Expression of Toll-like Receptors and Their Signaling Pathways in Rheumatoid Synovitis JOURNAL OF RHEUMATOLOGY Tamaki, Y., Takakubo, Y., Hirayama, T., Konttinen, Y. T., Goodman, S. B., Yamakawa, M., Takagi, M. 2011; 38 (5): 810-820

  Abstract

  Toll-like receptors (TLR) recognizing endogenous and exogenous danger signals could play a role in rheumatoid arthritis (RA). Our aim was to describe the presence, localization, and extent of expression of TLR and their adapters.TLR 1, 2, 3, 4, 5, 6, and 9 receptors, and myeloid differentiation primary response protein 88, Toll/interleukin receptor (TIR) domain-containing adapter protein MyD88 adapter-like, and TIR domain-containing adapter-inducing interferon/TIR-containing adapter molecule-1 adapters were analyzed in RA (n = 10) and osteoarthritis (OA; n = 5) samples using real-time polymerase chain reaction (PCR). Their colocalization with cellular markers CD68, CD15, CD3, CD4, CD8, CD20, dendritic cell lysosomal-associated membrane protein (DC-LAMP), CD123, and 5B5 was analyzed in double immunofluorescence staining.In RA, ß-actin standardized messenger RNA of TLR 2, 3, and 9 (p < 0.001) were particularly high. TLR 5 and 6 were also elevated (p < 0.05), but TLR 1 and 4 and adapters did not differ between RA and OA. In double-staining, TLR and adapters were strongly labeled in myeloid and plasmacytoid dendritic cells (DC), moderately in CD68+ type A lining cells/macrophages, and weakly to moderately in 5B5+ type B lining cells/fibroblasts. CD3+/CD4+ and CD3+/CD8+ T cells and CD20+ B cells in perivenular areas and in lymphoid follicles were moderately TLR- and weakly adapter-positive. In OA, TLR and adapters were weakly immunolabeled in vascular, lining, and inflammatory cells.RA synovium showed abundant expression of TLR. RA synovitis tissue seems to be responsive to TLR ligands. DC, type A cells/macrophages, and type B cells/fibroblasts are, in that order from highest to lowest, equipped with TLR, suggesting a hierarchical responsiveness. In RA, danger-associated molecular patterns to TLR interactions may particularly drive DC to autoinflammatory and autoimmune cascades/synovitis.

  View details for DOI 10.3899/jrheum.100732

  View details for Web of Science ID 000290780700006

  View details for PubMedID 21324962

• Effects of Intermittent Hydrostatic Pressure and BMP-2 on Osteoarthritic Human Chondrocyte Metabolism In Vitro JOURNAL OF ORTHOPAEDIC RESEARCH Smith, R. L., Lindsey, D. P., Dhulipala, L., Harris, A. H., Goodman, S. B., Maloney, W. J. 2011; 29 (3): 361-368

  Abstract

  This study examined effects of intermittent hydrostatic pressure (IHP) and a chondrogenic growth factor, bone morphogenetic protein-2 (BMP-2), on anabolic, catabolic, and other metabolic markers in human osteoarthritic (OA) chondrocytes in vitro.Articular chondrocytes, isolated from femoral OA cartilage and maintained in high-density monolayer culture, were examined for effects of BMP-2 and IHP on gene expression of matrix-associated proteins (aggrecan, type II collagen, and SOX9) and catabolic matrix metalloproteinases (MMP-2 and MMP-3) and culture medium levels of the metabolic markers MMP-2, nitric oxide (NO), and glycosaminoglycan (GAG). The results were analyzed using a mixed linear regression model to investigate the effects of load and growth factor concentration.IHP and BMP-2 modulated OA chondrocyte metabolism in accordance with growth factor concentration independently, without evidence of synergism or antagonism. Each type of stimulus acted independently on anabolic matrix gene expression. Type II collagen and SOX9 gene expression were stimulated by both IHP and BMP-2 whereas aggrecan was increased only by BMP-2. IHP exhibited a trend to decrease MMP-2 gene expression as a catabolic marker whereas BMP-2 did not. NO production was increased by addition of BMP-2 and IHP exhibited a trend for increased levels. GAG production was increased by BMP-2.This study confirmed the hypothesis that human OA chondrocytes respond to a specific type of mechanical load, IHP, through enhanced articular cartilage macromolecule gene expression and that IHP, in combination with a chondrogenic growth factor BMP-2, additively enhanced matrix gene expression without interactive effects.

  View details for DOI 10.1002/jor.21250

  View details for Web of Science ID 000287173500009

  View details for PubMedID 20882590

• Papers Presented at the Hip Society Meetings 2010 Editorial Comment CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B. 2011; 469 (2): 317-318

  View details for DOI 10.1007/s11999-010-1631-y

  View details for Web of Science ID 000286939300001

  View details for PubMedID 20963529

  View details for PubMedCentralID PMC3018188

• Noninvasive Monitoring of Placenta-Specific Transgene Expression by Bioluminescence Imaging PLOS ONE Fan, X., Ren, P., Dhal, S., Bejerano, G., Goodman, S. B., Druzin, M. L., Gambhir, S. S., Nayak, N. R. 2011; 6 (1)

  Abstract

  Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts.Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages.These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero.

  View details for DOI 10.1371/journal.pone.0016348

  View details for PubMedID 21283713

• Stem cell homing in musculoskeletal injury BIOMATERIALS Fong, E. L., Chan, C. K., Goodman, S. B. 2011; 32 (2): 395-409

  Abstract

  The regenerative potential of injured adult tissue suggests the physiological existence of cells capable of participating in the reparative process. Recent studies indicate that stem-like cells residing in tissues contribute to tissue repair and are replenished by precursor bone marrow-derived cells. Mesenchymal stromal cells (MSC) are among the candidates for reparative cells. These cells can potentially be mobilized into the circulation in response to injury signals and exert their reparative effects at the site of injury. Current therapies for musculoskeletal injuries pose unavoidable risks which can impede full recovery. Trafficking of MSC to the injury site and their subsequent participation in the regenerative process is thought to be a natural healing response that can be imitated or augmented by enhancing the endogenous MSC pool with exogenously administered MSC. Therefore, a promising alternative to the existing strategies employed in the treatment of musculoskeletal injuries is to reinforce the inherent reparative capacity of the body by delivering MSC harvested from the patient's own tissues to the site of injury. The aim of this review is to inform the reader of studies that have evaluated the intrinsic homing and regenerative abilities of MSC, with particular emphasis on the repair of musculoskeletal injuries. Research that supports the direct use of MSC (without in vitro differentiation into tissue-specific cells) will also be reported. Based on accruing evidence that the natural healing mechanism involves the recruitment of MSC and their subsequent reparative actions at the site of injury, as well as documented therapeutic response after the exogenous administration of MSC, the feasibility of the emerging strategy of instant stem-cell therapy will be proposed.

  View details for DOI 10.1016/j.biomaterials.2010.08.101

  View details for Web of Science ID 000285401500008

  View details for PubMedID 20933277

  View details for PubMedCentralID PMC2991369

• Continuous Infusion of UHMWPE Particles Induces Increased Bone Macrophages and Osteolysis Annual Scientific Meeting of the Knee-Society Ren, P., Irani, A., Huang, Z., Ma, T., Biswal, S., Goodman, S. B. SPRINGER. 2011: 113–22

  Abstract

  Aseptic loosening and periprosthetic osteolysis resulting from wear debris are major complications of total joint arthroplasty. Monocyte/macrophages are the key cells related to osteolysis at the bone-implant interface of joint arthroplasties. Whether the monocyte/macrophages found at the implant interface in the presence of polyethylene particles are locally or systemically derived is unknown.We therefore asked (1) whether macrophages associated with polyethylene particle-induced chronic inflammation are recruited locally or systemically and (2) whether the recruited macrophages are associated with enhanced osteolysis locally.Noninvasive in vivo imaging techniques (bioluminescence and microCT) were used to investigate initial macrophage migration systemically from a remote injection site to polyethylene wear particles continuously infused into the femoral canal. We used histologic and immunohistologic staining to confirm localization of migrated macrophages to the polyethylene particle-treated femoral canals and monitor cellular markers of bone remodeling.The values for bioluminescence were increased for animals receiving UHMWPE particles compared with the group in which the carrier saline was infused. At Day 8, the ratio of bioluminescence (operated femur divided by nonoperated contralateral femur of each animal) for the UHMWPE group was 13.95 ± 5.65, whereas the ratio for the saline group was 2.60 ± 1.14. Immunohistologic analysis demonstrated the presence of reporter macrophages in the UHMWPE particle-implanted femora only. MicroCT scans showed the bone mineral density for the group with both UHMWPE particles and macrophage was lower than the control groups.Infusion of clinically relevant polyethylene particles, similar to the human scenario, stimulated systemic migration of remotely injected macrophages and local net bone resorption.

  View details for DOI 10.1007/s11999-010-1645-5

  View details for PubMedID 21042895

• Use and Cost-Effectiveness of Intraoperative Acid-Fast Bacilli and Fungal Cultures in Assessing Infection of Joint Arthroplasties JOURNAL OF ARTHROPLASTY Wadey, V. M., Huddleston, J. I., Goodman, S. B., Schurman, D. J., Maloney, W. J., Baron, E. J. 2010; 25 (8): 1231-1234

  Abstract

  The objective of this study is to determine a protocol for collecting acid-fast bacilli (AFB) and fungal intraoperative cultures during orthopedic procedures. An observational study was undertaken. Four hundred forty-six AFB cultures and 486 fungal cultures were processed over a 2-year period. The number of positive cultures was determined. A protocol specific to handling these types of specimens was developed. Cost analysis was completed to determine both the time and money saved if the new protocol was implemented. The infrequency of positive AFB and fungal cultures in this study suggests that it is only necessary to routinely request AFB and fungal cultures on 1 of 5 samples. Implementation of this protocol has potential to lead to substantial cost reduction and resource savings without diminishing patient outcomes.

  View details for DOI 10.1016/j.arth.2009.08.018

  View details for Web of Science ID 000284749500009

  View details for PubMedID 19879728

• Synovial Tissue-Infiltrating Natural Killer Cells in Osteoarthritis and Periprosthetic Inflammation ARTHRITIS AND RHEUMATISM Huss, R. S., Huddleston, J. I., Goodman, S. B., Butcher, E. C., Zabel, B. A. 2010; 62 (12): 3799-3805

  Abstract

  Infiltrating immune cells play a central role in degenerative joint disease associated with osteoarthritis (OA) and particle-mediated periprosthetic osteolysis. The goal of this study was to characterize a newly identified population of synovial tissue-infiltrating natural killer (NK) cells obtained from patients with OA or patients with periprosthetic joint inflammation.Synovial and interfacial tissue samples were collected from patients with OA who were undergoing primary or revision total joint replacement (TJR) surgery. The histologic features of OA synovium obtained from patients undergoing primary surgery and interfacial tissue obtained from patients undergoing revision surgery were determined by immunohistochemistry and immunofluorescence. Synovial tissue-infiltrating NK cells were evaluated for the expression of surface receptors, using flow cytometry. Chemoattractant and cytokine protein and RNA levels in synovial and interfacial tissue and fluid were assessed by Luminex assay and real-time quantitative polymerase chain reaction. Cytokine production and degranulation by stimulated synovial tissue versus normal blood NK cells were evaluated by intracellular cytokine staining.NK cells comprised nearly 30% of the CD45+ mononuclear cell infiltrate in synovial tissue obtained from patients undergoing primary TJR and from patients undergoing revision TJR. NK cells from both groups expressed CXCR3, CCR5, L-selectin, α4 integrins, and cutaneous lymphocyte antigen. Synovial fluid from patients undergoing revision surgery contained elevated concentrations of the NK cell attractants CCL4, CCL5, CXCL9, and CXCL10; all levels in synovial fluid obtained from patients undergoing revision surgery were higher than those in synovial fluid from patients undergoing primary surgery. Cytokine-stimulated interferon-γ production was significantly impaired in NK cells derived from primary and revision TJRs compared with blood NK cells.NK cells are a principal tissue-infiltrating lymphocyte subset in patients with OA and patients with periprosthetic inflammation and display a quiescent phenotype that is consistent with postactivation exhaustion.

  View details for DOI 10.1002/art.27751

  View details for PubMedID 20848566

• Bilateral knee arthrodesis in a patient with common variable immunodeficiency. journal of arthroplasty Irani, A. R., Graw, B. P., Goodman, S. B. 2010; 25 (7): 1169 e13-6

  Abstract

  Patients with common variable immunodeficiency can present with debilitating arthritis. We present the case of a 42-year-old man with bilateral knee arthritis who underwent a right total knee arthroplasty that subsequently became infected. Five months after resection arthroplasty, his right leg spontaneously fused in extension, but his left knee was limited to an arc of motion between 90° and 110°. At the patient's request, he underwent a noninstrumented arthrodesis of the left knee. The patient now has bilateral arthrodeses and ambulates with a cane. While arthroplasty may be attempted in such patients, the increased risk of infection may potentially result in arthrodesis, possibly without instrumentation.

  View details for DOI 10.1016/j.arth.2009.07.005

  View details for PubMedID 19729268

• Effects of orthopedic polymer particles on chemotaxis of macrophages and mesenchymal stem cells. Journal of biomedical materials research. Part A Huang, Z., Ma, T., Ren, P., Smith, R. L., Goodman, S. B. 2010; 94 (4): 1264-1269

  Abstract

  Wear particles generated from total joint arthroplasty (TJA) stimulate macrophages to release chemokines. The role of chemokines released from wear particle-stimulated macrophages on the migration of macrophages and osteoprogenitor cells in vitro has not been elucidated. In this study, we challenged murine macrophages (RAW 264.7) with clinically relevant polymethyl methacrylate (PMMA, 1-10 microm) and ultra high molecular weight polyethylene (UHMWPE, 2-3 microm) particles. The chemotactic effects of the conditioned media (CM) were tested in vitro using human macrophages (THP-1) and human mesenchymal stem cells (MSCs) as the migrating cells. CM collected from both particle types had a chemotactic effect on human macrophages, which could be eliminated by monocyte chemotactic protein-1 (MCP-1) neutralizing antibody. Blocking the CCR1 receptor eliminated the chemotactic effect, while CCR2 antibody only partially decreased THP-1 cell migration. CM from PMMA but not UHMWPE-exposed macrophages led to chemotaxis of MSCs; this effect could be eliminated by macrophage inflammatory protein-1 alpha (MIP-1alpha) neutralizing antibody. Neither CCR1 nor CCR2 blocking antibodies showed an effect on the migration of MSCs. Chemokines released by macrophages stimulated by wear particles can have an effect on the migration of macrophages and MSCs. This effect seems to be dependent on the particle type, and may be modulated by MCP-1 and MIP-1alpha, however, more than one chemokine may be necessary for chemotaxis.

  View details for DOI 10.1002/jbm.a.32803

  View details for PubMedID 20694994

• Effects of orthopedic polymer particles on chemotaxis of macrophages and mesenchymal stem cells JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Huang, Z., Ma, T., Ren, P., Smith, R. L., Goodman, S. B. 2010; 94A (4): 1264-1269

  Abstract

  Wear particles generated from total joint arthroplasty (TJA) stimulate macrophages to release chemokines. The role of chemokines released from wear particle-stimulated macrophages on the migration of macrophages and osteoprogenitor cells in vitro has not been elucidated. In this study, we challenged murine macrophages (RAW 264.7) with clinically relevant polymethyl methacrylate (PMMA, 1-10 microm) and ultra high molecular weight polyethylene (UHMWPE, 2-3 microm) particles. The chemotactic effects of the conditioned media (CM) were tested in vitro using human macrophages (THP-1) and human mesenchymal stem cells (MSCs) as the migrating cells. CM collected from both particle types had a chemotactic effect on human macrophages, which could be eliminated by monocyte chemotactic protein-1 (MCP-1) neutralizing antibody. Blocking the CCR1 receptor eliminated the chemotactic effect, while CCR2 antibody only partially decreased THP-1 cell migration. CM from PMMA but not UHMWPE-exposed macrophages led to chemotaxis of MSCs; this effect could be eliminated by macrophage inflammatory protein-1 alpha (MIP-1alpha) neutralizing antibody. Neither CCR1 nor CCR2 blocking antibodies showed an effect on the migration of MSCs. Chemokines released by macrophages stimulated by wear particles can have an effect on the migration of macrophages and MSCs. This effect seems to be dependent on the particle type, and may be modulated by MCP-1 and MIP-1alpha, however, more than one chemokine may be necessary for chemotaxis.

  View details for DOI 10.1002/jbm.a.32803

  View details for Web of Science ID 000280860000029

  View details for PubMedCentralID PMC2919831

• Allograft alternatives: bone substitutes and beyond. Orthopedics Goodman, S. B. 2010; 33 (9): 661-?

  Abstract

  Excessive wear debris, deep infection, periprosthetic fracture, and other causes can lead to bone loss associated with total joint replacements. When performing revisions, surgeons are often preoccupied by the failed implant and the method of replacement, and neglect an opportunity to replenish lost bone. Thus, when formulating a plan for revision total joint replacement, the surgeon should consider not only the hardware that should be used, but also ways in which lost bone could be restored. Autograft bone provides the best source for osteoprogenitor cells, growth factors, and a scaffold. However, autograft is limited in supply, and is generally associated with another incision, dissection, and accompanying morbidity. Osteoconductive bone void fillers such as morselized cancellous allograft bone, polymeric scaffolds, and biodegradable ceramics each have their merits and deficiencies; however, all of these materials function as a scaffold only, without the ability to induce bone formation. Osteoinductive growth factors are essential to bone growth and remodeling; however, exogenous growth factors are expensive, are given in large nonphysiological doses, may yield unpredictable clinical results, and may have significant adverse effects. Demineralized bone matrix contains a scaffold and variable amounts of several growth factors. Recently, the use of mesenchymal stem cells and osteoprogenitors, together with a suitable scaffold carrier has gained increasing popularity. With the addition of appropriate growth factors, this combination can provide all the necessary components for osteogenesis. Future basic and clinical research will define the indications and outcomes for new combination products for reconstruction of lost bone associated with revision total joint replacement.

  View details for DOI 10.3928/01477447-20100722-31

  View details for PubMedID 20839690

• Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Ren, P., Huang, Z., Ma, T., Biswal, S., Smith, R. L., Goodman, S. B. 2010; 94A (3): 706-711

  Abstract

  Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra-high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2-day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 +/- 0.09-, 2.36 +/- 0.92-, and 10.32 +/- 7.61-fold, respectively. The values at same time points for saline-injected control group were 1.08 +/- 0.07-, 1.14 +/- 0.27-, and 1.14 +/- 0.35-fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis.

  View details for DOI 10.1002/jbm.a.32744

  View details for Web of Science ID 000280536300006

  View details for PubMedCentralID PMC2936785

• Minimal Incision Surgery as a Risk Factor for Early Failure of Total Hip Arthroplasty CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Graw, B. P., Woolson, S. T., Huddleston, H. G., Goodman, S. B., Huddleston, J. I. 2010; 468 (9): 2372-2376

  Abstract

  Minimal incision total hip arthroplasty (MI THA) techniques were developed to decrease postoperative pain and recovery time. Although these techniques have increased in popularity, the long-term survivorship of these procedures is unknown.We therefore investigated whether the time to revision in our referral practice was shorter for patients who underwent primary MI THA compared to primary traditional THA.We retrospectively reviewed 46 revision THAs performed during a 3-year period. We excluded revisions performed for infection and rerevisions. Patients with incisions less than or equal to 10 cm were defined as having had MI THA. Fifteen of the 46 patients (33%) had undergone primary MI THA. At the time of primary index THA, the mean ages of the MI and non-MI patients were 65 years and 55 years, respectively.The mean time to revision was 1.4 years for the MI patients compared with 14.7 years for the non-MI patients. Twelve of the 15 patients having MI THA required revision within 2 years of primary THA compared to 4 of the 31 patients without MI surgery (OR = 26.5, 95% CI 4.4-160.0). There were no differences between the groups with regard to age, gender, or body mass index. The most common reasons for revision in the MI THA group were intraoperative fracture and failure of femoral component osseointegration.Our data suggest MI THA may be a risk factor for early revision surgery and the long-term survival therefore may be lower than that for non-MI surgery.Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-010-1300-1

  View details for PubMedID 20352391

• Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability CYTOKINE Huang, Z., Ren, P., Ma, T., Smith, R. L., Goodman, S. B. 2010; 51 (3): 305-310

  Abstract

  Growth factors control the proliferation and differentiation of osteoprogenitor cells. This study explores the effects of modulating growth factors (VEGF, IGF-1, FGF-2 and BMP-2) on osteogenesis of mesenchymal stem cells (MSCs) in vitro. Constant and profiled delivery protocols, in accordance with protein expression in vitro, were applied to deliver or neutralize growth factors. Cell number, alkaline phosphatase (ALP-2) and osteocalcin (OC) expression, and mineralization were measured as outcome variables. Profiled addition of VEGF increased MSC proliferation. Constant and profiled application of FGF-2 and neutralization of IGF-1 and BMP-2 decreased ALP-2 levels. Profiled addition of BMP-2 vastly increased OC release from MSCs, but constant addition of IGF-1, constant and profiled neutralization of IGF-1 and FGF-2 reduced OC levels. Constant addition of IGF-1 and FGF-2, as well as profiled loading of FGF-2 decreased mineralization of MSCs. This study indicated that endogenous IGF-1 and FGF-2 are essential to osteogenesis; excess IGF-1 and FGF-2 were inhibitory to bone formation. Selective, temporally specific addition of growth factors, such as BMP-2 and VEGF appears to be an important strategy to enhance osteogenesis.

  View details for DOI 10.1016/j.cyto.2010.06.002

  View details for PubMedID 20580248

• Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging. Journal of biomedical materials research. Part A Ren, P., Huang, Z., Ma, T., Biswal, S., Smith, R. L., Goodman, S. B. 2010; 94 (3): 706-711

  Abstract

  Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra-high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2-day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 +/- 0.09-, 2.36 +/- 0.92-, and 10.32 +/- 7.61-fold, respectively. The values at same time points for saline-injected control group were 1.08 +/- 0.07-, 1.14 +/- 0.27-, and 1.14 +/- 0.35-fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis.

  View details for DOI 10.1002/jbm.a.32744

  View details for PubMedID 20213815

• OP-1 (BMP-7) stimulates osteoprogenitor cell differentiation in the presence of polymethylmethacrylate particles. Journal of biomedical materials research. Part A Kann, S., Chiu, R., Ma, T., Goodman, S. B. 2010; 94 (2): 485-488

  Abstract

  Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation, proliferation, and mineralization of osteoprogenitor cells in vitro. In this study, we investigated the effects of OP-1 (BMP-7) on the osteogenesis of MC3T3-E1 osteoprogenitor cells exposed to PMMA particles in vitro. MC3T3-E1 cells challenged with PMMA particles on the 1st day of differentiation in osteogenic culture showed a significant dose-dependent decrease in mineralization and alkaline phosphatase expression over a 20-day culture period. Exposure of these cells to OP-1 (200 ng/mL) during days 1-4, 1-20, and 4-20 in the presence of PMMA particles resulted in significant increases in mineralization and alkaline phosphatase expression at all particle doses. Addition of OP-1 to MC3T3-E1 cultures challenged with PMMA particles on the 4th day of differentiation in osteogenic media also resulted in significant increases in mineralization and alkaline phosphatase expression. This study has shown that OP-1 stimulates osteogenesis in MC3T3-E1 osteoprogenitor cells that have been inhibited by PMMA particles. Local administration of OP-1 to the site of osteolysis may be a potential adjunctive therapy to reverse the bone destruction due to wear particles.

  View details for DOI 10.1002/jbm.a.32712

  View details for PubMedID 20186767

• OP-1 (BMP-7) stimulates osteoprogenitor cell differentiation in the presence of polymethylmethacrylate particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Kann, S., Chiu, R., Ma, T., Goodman, S. B. 2010; 94A (2): 485-488

  Abstract

  Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation, proliferation, and mineralization of osteoprogenitor cells in vitro. In this study, we investigated the effects of OP-1 (BMP-7) on the osteogenesis of MC3T3-E1 osteoprogenitor cells exposed to PMMA particles in vitro. MC3T3-E1 cells challenged with PMMA particles on the 1st day of differentiation in osteogenic culture showed a significant dose-dependent decrease in mineralization and alkaline phosphatase expression over a 20-day culture period. Exposure of these cells to OP-1 (200 ng/mL) during days 1-4, 1-20, and 4-20 in the presence of PMMA particles resulted in significant increases in mineralization and alkaline phosphatase expression at all particle doses. Addition of OP-1 to MC3T3-E1 cultures challenged with PMMA particles on the 4th day of differentiation in osteogenic media also resulted in significant increases in mineralization and alkaline phosphatase expression. This study has shown that OP-1 stimulates osteogenesis in MC3T3-E1 osteoprogenitor cells that have been inhibited by PMMA particles. Local administration of OP-1 to the site of osteolysis may be a potential adjunctive therapy to reverse the bone destruction due to wear particles.

  View details for DOI 10.1002/jbm.a.32712

  View details for Web of Science ID 000279482600017

• Effects of Tensile Strain and Fluid Flow on Osteoarthritic Human Chondrocyte Metabolism In Vitro JOURNAL OF ORTHOPAEDIC RESEARCH Mawatari, T., Lindsey, D. P., Harris, A. H., Goodman, S. B., Maloney, W. J., Smith, R. L. 2010; 28 (7): 907-913

  Abstract

  This study examined the hypothesis that tensile strain and fluid flow differentially influence osteoarthritic human chondrocyte metabolism. Primary high-density monolayer chondrocytes cultures were exposed to varying magnitudes of tensile strain and fluid-flow using a four-point bending system. Metabolic changes were quantified by real-time PCR measurement of aggrecan, IL-6, SOX-9, and type II collagen gene expression, and by determination of nitric oxide levels in the culture medium. A linear regression model was used to investigate the roles of strain, fluid flow, and their interaction on metabolic activity. Aggrecan, type II collagen, and SOX9 mRNA expression were negatively correlated to increases in applied strain and fluid flow. An effect of the strain on the induction of nitric oxide release and IL-6 gene expression varied by level of fluid flow (and visa versa). This interaction between strain and fluid flow was negative for nitric oxide and positive for IL-6. These results confirm that articular chondrocyte metabolism is responsive to tensile strain and fluid flow under in vitro loading conditions. Although the articular chondrocytes reacted to the mechanically applied stress, it was notable that there was a differential effect of tensile strain and fluid flow on anabolic and catabolic markers.

  View details for DOI 10.1002/jor.21085

  View details for PubMedID 20063382

• Polymethylmethacrylate particle exposure causes changes in p38 MAPK and TGF-beta signaling in differentiating MC3T3-E1 cells JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Ma, G. K., Chiu, R., Huang, Z., Pearl, J., Ma, T., Smith, R. L., Goodman, S. B. 2010; 94A (1): 234-240

  Abstract

  Periprosthetic osteolysis of joint replacements caused by wear debris is a significant complication of joint replacements. Polymethylmethacrylate (PMMA) particles have been shown to inhibit osteogenic differentiation, but the molecular mechanism has not been previously determined. In this study, we exposed differentiating MC3T3-E1 preostoblast cells to PMMA particles and determined the changes that occurred with respect to p38 mitogen-activated protein kinase (MAPK) activity and the transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP) signaling pathways. In the absence of particles, MC3T3-E1 cells demonstrate activation of p38 MAPK on day 8 of differentiation; however, when treated with PMMA particles, differentiating MC3T3-E1 cells demonstrate the suppression of p38 activity on day 8 and show activation of p38 on days 1 and 4. On day 4 of particle exposure, the differentiating MC3T3-E1 cells show significant downregulation of TGF-beta1 expression, which is involved in osteoblast differentiation, and a significant upregulation of the expression of BMP3 and Sclerostin (SOST), which are negative regulators of osteoblast differentiation. By day 8 of particle exposure, the changes in TGF-beta1, BMP3, and SOST expression are opposite of those seen on day 4. This study has demonstrated the distinct changes in the molecular profile of MC3T3-E1 cells during particle-induced inhibition of osteoblast differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

  View details for DOI 10.1002/jbm.a.32686

  View details for Web of Science ID 000278400800025

• The relationship of polyethylene wear to particle size, distribution, and number: A possible factor explaining the risk of osteolysis after hip arthroplasty. Journal of biomedical materials research. Part B, Applied biomaterials Gallo, J., Slouf, M., Goodman, S. B. 2010; 94 (1): 171-177

  Abstract

  The most critical factor in the development of periprosthetic osteolysis (OL) in total hip arthroplasty (THA) is the biological reaction to wear debris. This reaction is dependent, in part, on the size and concentration of particles, which are determined predominantly by the polyethylene (PE) wear rate. This implies that the risk for developing OL and prosthesis failure can be estimated from wear measurements. We developed a computational algorithm for calculating the total number of PE particles for volumetric wear when particle size and distribution are known. We found that: (i) total number of PE wear particles decreases up to 5 orders of magnitude if the average size of particles increases and the total volumetric wear remains constant; (ii) total amount of PE wear particles decreases up to 4 orders of magnitude if the width of the distribution increases and total volumetric wear remains constant; (iii) for the same volumetric wear, the number of particles significantly decreases/increases with the increase/decrease in their average size and range. These findings suggest that the risk for the development of OL in THA cannot be simply estimated from the volumetric wear alone.

  View details for DOI 10.1002/jbm.b.31638

  View details for PubMedID 20524192

• The relationship of polyethylene wear to particle size, distribution, and number: A possible factor explaining the risk of osteolysis after hip arthroplasty JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Gallo, J., Slouf, M., Goodman, S. B. 2010; 94B (1): 171-177

  Abstract

  The most critical factor in the development of periprosthetic osteolysis (OL) in total hip arthroplasty (THA) is the biological reaction to wear debris. This reaction is dependent, in part, on the size and concentration of particles, which are determined predominantly by the polyethylene (PE) wear rate. This implies that the risk for developing OL and prosthesis failure can be estimated from wear measurements. We developed a computational algorithm for calculating the total number of PE particles for volumetric wear when particle size and distribution are known. We found that: (i) total number of PE wear particles decreases up to 5 orders of magnitude if the average size of particles increases and the total volumetric wear remains constant; (ii) total amount of PE wear particles decreases up to 4 orders of magnitude if the width of the distribution increases and total volumetric wear remains constant; (iii) for the same volumetric wear, the number of particles significantly decreases/increases with the increase/decrease in their average size and range. These findings suggest that the risk for the development of OL in THA cannot be simply estimated from the volumetric wear alone.

  View details for DOI 10.1002/jbm.b.31638

  View details for Web of Science ID 000278697400020

• Polymethylmethacrylate particle exposure causes changes in p38 MAPK and TGF-beta signaling in differentiating MC3T3-E1 cells. Journal of biomedical materials research. Part A Ma, G. K., Chiu, R., Huang, Z., Pearl, J., Ma, T., Smith, R. L., Goodman, S. B. 2010; 94 (1): 234-240

  Abstract

  Periprosthetic osteolysis of joint replacements caused by wear debris is a significant complication of joint replacements. Polymethylmethacrylate (PMMA) particles have been shown to inhibit osteogenic differentiation, but the molecular mechanism has not been previously determined. In this study, we exposed differentiating MC3T3-E1 preostoblast cells to PMMA particles and determined the changes that occurred with respect to p38 mitogen-activated protein kinase (MAPK) activity and the transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP) signaling pathways. In the absence of particles, MC3T3-E1 cells demonstrate activation of p38 MAPK on day 8 of differentiation; however, when treated with PMMA particles, differentiating MC3T3-E1 cells demonstrate the suppression of p38 activity on day 8 and show activation of p38 on days 1 and 4. On day 4 of particle exposure, the differentiating MC3T3-E1 cells show significant downregulation of TGF-beta1 expression, which is involved in osteoblast differentiation, and a significant upregulation of the expression of BMP3 and Sclerostin (SOST), which are negative regulators of osteoblast differentiation. By day 8 of particle exposure, the changes in TGF-beta1, BMP3, and SOST expression are opposite of those seen on day 4. This study has demonstrated the distinct changes in the molecular profile of MC3T3-E1 cells during particle-induced inhibition of osteoblast differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

  View details for DOI 10.1002/jbm.a.32686

  View details for PubMedID 20166219

• Cellular chemotaxis induced by wear particles from joint replacements BIOMATERIALS Goodman, S. B., Ma, T. 2010; 31 (19): 5045-5050

  Abstract

  The destruction of bone around joint replacements (periprosthetic osteolysis) is an adverse biological response associated with the generation of excessive wear particles. Wear debris from the materials used for joint replacements stimulate a chronic inflammatory and foreign body reaction that leads to increased osteoclast differentiation and maturation, and decreased bone formation. Wear debris induces both local and systemic trafficking of inflammatory cells to the site of particle generation. Recent studies have shown that this effect is mediated primarily by chemotactic cytokines (chemokines) including macrophage chemotactic protein-1 (MCP-1, also known as CCL2), macrophage inhibitory protein-1 (MIP-1), Interleukin-8 (IL-8 or CXCL8) and others. These ligands migrate along a concentration gradient to interact with G-protein-linked transmembrane receptors on the cell surface. Chemokines are involved in the innate and adaptive immune responses, angiogenesis, wound healing and tissue repair. In vitro, in vivo and tissue retrieval studies have shown that chemokine-directed systemic trafficking of polymorphonuclear leukocytes and cells of the monocyte/macrophage lineage to wear particles result in the release of pro-inflammatory factors and subsequent bone loss. Modulation of the chemokine ligand-receptor axis is a potential strategy to mitigate the adverse effects of wear particles from joint replacements.

  View details for DOI 10.1016/j.biomaterials.2010.03.046

  View details for PubMedID 20398931

• Aseptic versus septic revision total knee arthroplasty: Patient satisfaction, outcome and quality of life improvement KNEE Patil, N., Lee, K., Huddleston, J. I., Harris, A. H., Goodman, S. B. 2010; 17 (3): 200-203

  Abstract

  We prospectively compared the clinical outcomes and patient satisfaction rates of aseptic (n=30) versus septic revision TKA (n=15) at a mean follow-up of 40 months. We hypothesized that the clinical results of septic revision TKA would be inferior to aseptic revision TKA. The indication for revision in aseptic group was stiffness in 11 patients, aseptic loosening in 13, patellar loosening or maltracking in 6 patients. Patients operated for infection had better post-operative Knee Society Scores (KSS), Function Scores and SF-36 Mental Scores than aseptic group but there were no significant differences in the satisfaction rates. Patients operated for infection had more improvement in their KSS (p=0.004) and Function Scores (p=0.02) than patients revised for stiffness. Moreover, patients operated on for patellar problems had higher satisfaction rates than patients revised for stiffness (p=0.01) or aseptic loosening (p=0.01). Thus, patients undergoing septic revision TKA had better outcomes compared to those with aseptic revision TKA. However, in the aseptic group, revision TKA for stiffness was associated with the poorest outcomes. The indication for aseptic revision is an important variable when discussing treatment and outcome with patients.

  View details for DOI 10.1016/j.knee.2009.09.001

  View details for PubMedID 19875297

• Patellar Management in Revision Total Knee Arthroplasty JOURNAL OF ARTHROPLASTY Patil, N., Lee, K., Huddleston, J. I., Harris, A. H., Goodman, S. B. 2010; 25 (4): 589-593

  Abstract

  The management of the patella during revision total knee arthroplasty (TKA) depends on the indication for revision, the type and stability of the patellar component in place, and availability of bone stock. We prospectively compared the clinical outcome and satisfaction rates in revision TKA patients managed with patellar resurfacing (n = 13, group I) to retention of the patellar component (n = 22, group II) or patelloplasty (n = 11, group III) at a minimum follow-up of 2 years. There were no differences in the improvement of Knee Society Scores, Short-Form 36 Scores, and satisfaction rates between the groups. There were no revision surgeries for patellar component failure or patellar fractures. Satisfactory results can be achieved using a variety of methods of patellar management in revision TKA by individualizing the treatment modality depending on the clinical scenario.

  View details for DOI 10.1016/j.arth.2009.04.009

  View details for PubMedID 19493648

• Polymethylmethacrylate Particles Impair Osteoprogenitor Viability and Expression of Osteogenic Transcription Factors Runx2, Osterix, and Dlx5 JOURNAL OF ORTHOPAEDIC RESEARCH Chiu, R., Smith, K. E., Ma, G. K., Ma, T., Smith, R. L., Goodman, S. B. 2010; 28 (5): 571-577

  Abstract

  Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation of osteoprogenitor cells, but the mechanism of this inhibitory effect has not been investigated. We hypothesize that the inhibitory effects of PMMA particles involve impairment of osteoprogenitor viability and direct inhibition of transcription factors that regulate osteogenesis. We challenged MC3T3-E1 osteoprogenitors with PMMA particles and examined the effects of these materials on osteoprogenitor viability and expression of transcription factors Runx2, osterix, Dlx5, and Msx2. MC3T3-E1 cells treated with PMMA particles over a 72-h period showed a significant reduction in cell viability and proliferation as indicated by a dose- and time-dependent increase in supernatant levels of lactate dehydrogenase, an intracellular enzyme released from dead cells, a dose-dependent decrease in cell number and BrdU uptake, and the presence of large numbers of positively labeled Annexin V-stained cells. The absence of apoptotic cells on TUNEL assay indicated that cell death occurred by necrosis, not apoptosis. MC3T3-E1 cells challenged with PMMA particles during the first 6 days of differentiation in osteogenic medium showed a significant dose-dependent decrease in the RNA expression of Runx2, osterix, and Dlx5 on all days of measurement, while the RNA expression of Msx2, an antagonist of Dlx5-induced osteogenesis, remained relatively unaffected. These results indicate that PMMA particles impair osteoprogenitor viability and inhibit the expression of transcription factors that promote osteoprogenitor differentiation.

  View details for DOI 10.1002/jor.21035

  View details for PubMedID 20014320

• Titanium particles modulate expression of Toll-like receptor proteins JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Pajarinen, J., Mackiewicz, Z., Pollanen, R., Takagi, M., Epstein, N. J., Ma, T., Goodman, S. B., Konttinen, Y. T. 2010; 92A (4): 1528-1537

  Abstract

  The role of Toll-like receptors (TLRs) responding to microbial remnants, indolent biofilms or cellular byproducts in aseptic loosening of joint replacements is unknown. Thus, the effect of titanium (Ti) particles on TLR protein levels was evaluated. To create a model of particle-induced inflammation, an intramedullary stainless steel rod with and without Ti particles was bilaterally placed in the femora of 14 mice. The animals were sacrificed at 2 or 10 weeks postoperatively and paraffin-embedded femur sections were evaluated for TLR1, 2, 4, 5, 8, and 9 proteins using immunohistochemistry. Decrease in the number of TLR immunoreactive cells was observed between weeks 2 and 10 in both settings. Furthermore, in the presence of Ti particles, the numbers of TLR immunoreactive cells were lower than in the presence of rod only at both time points, suggesting downregulation of TLR expression by Ti-particles per se. Accordingly, in a short-term 24 h stimulation, downregulation of TLR4 mRNA (p < 0.02) was observed in vitro in RAW 264.7 cells challenged with Ti particles. Results suggest that after an initial inflammatory stage, TLRs are downregulated in response to Ti particles, possibly to inhibit excessive inflammation, although TLR downregulation might at the same time render tissues more susceptible to pathogens.

  View details for DOI 10.1002/jbm.a.32495

  View details for Web of Science ID 000274541500032

• Titanium particles modulate expression of Toll-like receptor proteins. Journal of biomedical materials research. Part A Pajarinen, J., Mackiewicz, Z., Pöllänen, R., Takagi, M., Epstein, N. J., Ma, T., Goodman, S. B., Konttinen, Y. T. 2010; 92 (4): 1528-1537

  Abstract

  The role of Toll-like receptors (TLRs) responding to microbial remnants, indolent biofilms or cellular byproducts in aseptic loosening of joint replacements is unknown. Thus, the effect of titanium (Ti) particles on TLR protein levels was evaluated. To create a model of particle-induced inflammation, an intramedullary stainless steel rod with and without Ti particles was bilaterally placed in the femora of 14 mice. The animals were sacrificed at 2 or 10 weeks postoperatively and paraffin-embedded femur sections were evaluated for TLR1, 2, 4, 5, 8, and 9 proteins using immunohistochemistry. Decrease in the number of TLR immunoreactive cells was observed between weeks 2 and 10 in both settings. Furthermore, in the presence of Ti particles, the numbers of TLR immunoreactive cells were lower than in the presence of rod only at both time points, suggesting downregulation of TLR expression by Ti-particles per se. Accordingly, in a short-term 24 h stimulation, downregulation of TLR4 mRNA (p < 0.02) was observed in vitro in RAW 264.7 cells challenged with Ti particles. Results suggest that after an initial inflammatory stage, TLRs are downregulated in response to Ti particles, possibly to inhibit excessive inflammation, although TLR downregulation might at the same time render tissues more susceptible to pathogens.

  View details for DOI 10.1002/jbm.a.32495

  View details for PubMedID 19425045

• Treatment of irradiated poststernotomy sternal nonunion with autologous stem cell-impregnated bone matrix and sternal plating JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Timek, T. A., Goodman, S. B., Whyte, R. I. 2010; 139 (3): 788-789

  View details for DOI 10.1016/j.jtcvs.2009.10.037

  View details for Web of Science ID 000274735400044

  View details for PubMedID 20038477

• Biocompatibility of poly(ethylene glycol)/poly(acrylic acid) interpenetrating polymer network hydrogel particles in RAW 264.7 macrophage and MG-63 osteoblast cell lines. Journal of biomedical materials research. Part A Yim, E. S., Zhao, B., Myung, D., Kourtis, L. C., Frank, C. W., Carter, D., Smith, R. L., Goodman, S. B. 2009; 91 (3): 894-902

  Abstract

  Hydrogel polymers comprise a novel category of synthetic materials being investigated for use in cartilage replacement. One candidate compound, a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN), was developed for use in corneal prostheses and was recently engineered for potential orthopedic use. The current study examined the effects of particles of this compound on two cell lines (MG-63 osteoblast-like cells and RAW 264.7 macrophages) over a 48-h time course. To mimic the effects of wear debris, particles of the compound were generated and introduced to the cells. In the MG-63 cell line, the particles had no significant effect on cell viability measured by PicoGreen assay and trypan blue exclusion. In contrast, a significant decrease in cell viability was detected in the Raw 264.7 macrophage cells at the final timepoint with the highest concentration of hydrogel (3.0% v:v). A concentration- and time-dependent increase in TNF-alpha release characteristic of other known biocompatible materials was also detected in RAW 264.7 cells, but nitric oxide and interleukin (IL)-1beta showed no response. In addition, the MG-63 cell line demonstrated no IL-6 response. Particles of the PEG/PAA IPN thus seem to stimulate biological responses similar to those in other biocompatible materials.

  View details for DOI 10.1002/jbm.a.32311

  View details for PubMedID 19072924

• Biocompatibility of poly(ethylene glycol)/poly(acrylic acid) interpenetrating polymer network hydrogel particles in RAW 264.7 macrophage and MG-63 osteoblast cell lines JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Yim, E. S., Zhao, B., Myung, D., Kourtis, L. C., Frank, C. W., Carter, D., Smith, R. L., Goodman, S. B. 2009; 91A (3): 894-902

  Abstract

  Hydrogel polymers comprise a novel category of synthetic materials being investigated for use in cartilage replacement. One candidate compound, a poly(ethylene glycol)/poly(acrylic acid) (PEG/PAA) interpenetrating polymer network (IPN), was developed for use in corneal prostheses and was recently engineered for potential orthopedic use. The current study examined the effects of particles of this compound on two cell lines (MG-63 osteoblast-like cells and RAW 264.7 macrophages) over a 48-h time course. To mimic the effects of wear debris, particles of the compound were generated and introduced to the cells. In the MG-63 cell line, the particles had no significant effect on cell viability measured by PicoGreen assay and trypan blue exclusion. In contrast, a significant decrease in cell viability was detected in the Raw 264.7 macrophage cells at the final timepoint with the highest concentration of hydrogel (3.0% v:v). A concentration- and time-dependent increase in TNF-alpha release characteristic of other known biocompatible materials was also detected in RAW 264.7 cells, but nitric oxide and interleukin (IL)-1beta showed no response. In addition, the MG-63 cell line demonstrated no IL-6 response. Particles of the PEG/PAA IPN thus seem to stimulate biological responses similar to those in other biocompatible materials.

  View details for DOI 10.1002/jbm.a.32311

  View details for Web of Science ID 000271588800027

• Thrombin-Activatable Carboxypeptidase B Cleavage of Osteopontin Regulates Neutrophil Survival and Synoviocyte Binding in Rheumatoid Arthritis ARTHRITIS AND RHEUMATISM Sharif, S. A., Du, X., Myles, T., Song, J. J., Price, E., Lee, D. M., Goodman, S. B., Nagashima, M., Morser, J., Robinson, W. H., Leung, L. L. 2009; 60 (10): 2902-2912

  Abstract

  Osteopontin (OPN) is a proinflammatory cytokine that plays an important role in the pathogenesis of rheumatoid arthritis (RA). OPN can be cleaved by thrombin, resulting in OPN-R and exposing the cryptic C-terminal alpha4beta1 and alpha9beta1 integrin-binding motif (SVVYGLR). Thrombin-activatable carboxypeptidase B (CPB), also called thrombin-activatable fibrinolysis inhibitor, removes the C-terminal arginine from OPN-R, generating OPN-L and abrogating its enhanced cell binding. We undertook this study to investigate the roles of OPN-R and OPN-L in synoviocyte adhesion, which contributes to the formation of invasive pannus, and in neutrophil survival, which affects inflammatory infiltrates in RA.Using specifically developed enzyme-linked immunosorbent assays, we tested the synovial fluid of patients with RA, osteoarthritis (OA), and psoriatic arthritis (PsA) to determine OPN-R, OPN-L, and full-length OPN (OPN-FL) levels.Elevated levels of OPN-R and OPN-L were found in synovial fluid samples from RA patients, but not in samples from OA or PsA patients. Increased levels of OPN-R and OPN-L correlated with increased levels of multiple inflammatory cytokines, including tumor necrosis factor alpha and interleukin-6. Immunohistochemical analyses revealed robust expression of OPN-FL, but only minimal expression of OPN-R, in RA synovium, suggesting that cleaved OPN is released into synovial fluid. In cellular assays, OPN-FL, and to a lesser extent OPN-R and OPN-L, had an antiapoptotic effect on neutrophils. OPN-R augmented RA fibroblast-like synoviocyte binding mediated by SVVYGLR binding to alpha4beta1, whereas OPN-L did not.Thrombin activation of OPN (resulting in OPN-R) and its subsequent inactivation by thrombin-activatable CPB (generating OPN-L) occurs locally within inflamed joints in RA. Our data suggest that thrombin-activatable CPB plays a central homeostatic role in RA by regulating neutrophil viability and reducing synoviocyte adhesion.

  View details for DOI 10.1002/art.24814

  View details for PubMedID 19790060

• Retroperitoneal hematoma: an unusual cause of pain after total hip arthroplasty. journal of arthroplasty Pouliot, M. A., Lee, K. B., Goodman, S. B. 2009; 24 (7): 1144 e9-12

  Abstract

  Pain following total hip arthroplasty due to impingement of the iliopsoas is a recognized complication of the procedure with a reported incidence as high as 4.3%. The pain is most often due to direct mechanical irritation of the iliopsoas due to a malpositioned or oversized acetabular cup. Definitive treatment of iliopsoas impingement often requires surgical revision or iliopsoas tenotomy, although many cases remain undiagnosed or are managed conservatively. We present an unusual case of pain after total hip arthroplasty due to a large retroperitoneal hematoma secondary to acetabular cup irritation of the iliopsoas tendon. This case represents a potentially important complication of undiagnosed or conservatively managed iliopsoas impingement, particularly in patients taking anticoagulants or antiplatelet medications.

  View details for DOI 10.1016/j.arth.2008.07.012

  View details for PubMedID 18848423

• Third-degree heart block associated with bupivacaine infusion following total knee arthroplasty. A case report. journal of bone and joint surgery. American volume Hay, D. C., Mayle, R. E., Goodman, S. B. 2009; 91 (9): 2238-2240

  View details for DOI 10.2106/JBJS.H.00723

  View details for PubMedID 19724003

• Third-Degree Heart Block Associated with Bupivacaine Infusion Following Total Knee Arthroplasty A Case Report JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Hay, D. C., Mayle, R. E., Goodman, S. B. 2009; 91A (9): 2238-2240

  View details for DOI 10.2106/JBJS.H.00723

  View details for Web of Science ID 000269460400023

• Biocompatibility of total joint replacements: A review. Journal of biomedical materials research. Part A Goodman, S. B., Gómez Barrena, E., Takagi, M., Konttinen, Y. T. 2009; 90 (2): 603-618

  Abstract

  Total joint replacement is one of the most clinically successful, cost-effective surgical procedures. These operations have been shown to improve pain, function and mobility in patients with end-stage arthritis. However, joint replacements that will allow full, unrestricted, high impact activities and last the patient's lifetime have not yet been devised. This is due to biocompatibility issues related to material science, biomechanics, and host responses. In this review, three issues that are highly pertinent to biocompatibility of joint replacements are examined. These topics include how implants initially osseointegrate within bone, potential adverse effects of byproducts of wear that can lead to aseptic loosening and periprosthetic osteolysis, and the potential for new bearing surfaces to extend the lifetime of implants. A clear understanding of these important issues will facilitate the development of novel strategies to improve the longevity and function of implants for joint replacement in the future.

  View details for DOI 10.1002/jbm.a.32063

  View details for PubMedID 18508337

• Biocompatibility of total joint replacements: A review JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S. B., Barrena, E. G., Takagi, M., Konttinen, Y. T. 2009; 90A (2): 603-618

  Abstract

  Total joint replacement is one of the most clinically successful, cost-effective surgical procedures. These operations have been shown to improve pain, function and mobility in patients with end-stage arthritis. However, joint replacements that will allow full, unrestricted, high impact activities and last the patient's lifetime have not yet been devised. This is due to biocompatibility issues related to material science, biomechanics, and host responses. In this review, three issues that are highly pertinent to biocompatibility of joint replacements are examined. These topics include how implants initially osseointegrate within bone, potential adverse effects of byproducts of wear that can lead to aseptic loosening and periprosthetic osteolysis, and the potential for new bearing surfaces to extend the lifetime of implants. A clear understanding of these important issues will facilitate the development of novel strategies to improve the longevity and function of implants for joint replacement in the future.

  View details for DOI 10.1002/jbm.a.32063

  View details for Web of Science ID 000267814100033

• Analysis of Bone Mineral Density and Bone Turnover in the Presence of Polymethylmethacrylate Particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Zilber, S., Lee, S. W., Smith, R. L., Biswal, S., Goodman, S. B. 2009; 90B (1): 362-367

  Abstract

  Polymethylmethacrylate (PMMA) particles generated from joint arthroplasties appear to contribute to aseptic implant loosening through inflammation-induced periprosthetic osteolysis. However, osteolysis appears to be multifactorial; whether a direct link exists between PMMA particles and osteolysis in vivo is unproven. With the aim to define the relationship between PMMA particles and osteolysis, the authors analyzed the bone mineral density, using microCT scans preoperatively, the first day postoperatively and then every 7-10 days for 32 days, and bone turnover, using (18)F-fluoride positron emission tomography scanner (PET scan) at 8 weeks in four groups of mice that had undergone intramedullary femoral injection. The experimental group of five mice was injected with PMMA particles, and compared with two negative control groups (no injection and injection with the carrier, phosphate-buffered saline) and one positive control group (injection of PMMA particles contaminated with endotoxin). There was no significant change in bone mineral density with addition of PMMA particles, and no evidence of osteolysis. However, bone turnover was increased in the presence of PMMA particles. Even though a direct link between PMMA particles and osteolysis was not found in the short term, PMMA particles appear to influence the regenerative capacity of bone.

  View details for DOI 10.1002/jbm.b.31293

  View details for Web of Science ID 000267298500041

• Analysis of bone mineral density and bone turnover in the presence of polymethylmethacrylate particles. Journal of biomedical materials research. Part B, Applied biomaterials Zilber, S., Lee, S. W., Smith, R. L., Biswal, S., Goodman, S. B. 2009; 90 (1): 362-367

  Abstract

  Polymethylmethacrylate (PMMA) particles generated from joint arthroplasties appear to contribute to aseptic implant loosening through inflammation-induced periprosthetic osteolysis. However, osteolysis appears to be multifactorial; whether a direct link exists between PMMA particles and osteolysis in vivo is unproven. With the aim to define the relationship between PMMA particles and osteolysis, the authors analyzed the bone mineral density, using microCT scans preoperatively, the first day postoperatively and then every 7-10 days for 32 days, and bone turnover, using (18)F-fluoride positron emission tomography scanner (PET scan) at 8 weeks in four groups of mice that had undergone intramedullary femoral injection. The experimental group of five mice was injected with PMMA particles, and compared with two negative control groups (no injection and injection with the carrier, phosphate-buffered saline) and one positive control group (injection of PMMA particles contaminated with endotoxin). There was no significant change in bone mineral density with addition of PMMA particles, and no evidence of osteolysis. However, bone turnover was increased in the presence of PMMA particles. Even though a direct link between PMMA particles and osteolysis was not found in the short term, PMMA particles appear to influence the regenerative capacity of bone.

  View details for DOI 10.1002/jbm.b.31293

  View details for PubMedID 19090495

• Cementless Femoral Prostheses Cost More to Implant than Cemented Femoral Prostheses CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Unnanuntana, A., Dimitroulias, A., Bolognesi, M. P., Hwang, K. L., Goodman, S. B., Marcus, R. E. 2009; 467 (6): 1546-1551

  Abstract

  Prosthetic cost contributes greatly to the overall expense of THA. A key question, therefore, in the selection of implant technique is whether any price difference exists between a cementless and a cemented femoral prosthesis. We evaluated the price difference between the most commonly used cemented and cementless femoral stems at three high-volume academic medical centers. Each hospital's costs for prostheses from the manufacturers were recorded. The average cost of implanting a cementless femoral prosthesis was $296 more than the average cost of implanting a cemented femoral stem, even with the additional expense of two batches of bone cement and the accessories commonly used to achieve a third-generation cementing technique. The price difference was less variable if the cost of the prostheses from only the primary implant supplier for each institution was considered. As the number of THAs performed per year continues to escalate, implantation of a cemented femoral component remains an attractive method of fixation from an economic standpoint. Level of Evidence: Level III, economic and decision analysis. See the Guidelines for Authors for a complete description of levels of evidence.

  View details for DOI 10.1007/s11999-008-0485-z

  View details for Web of Science ID 000265575500025

  View details for PubMedID 18781368

  View details for PubMedCentralID PMC2674154

• Efficacy of a p38 mitogen activated protein kinase inhibitor in mitigating an established inflammatory reaction to polyethylene particles in vivo. Journal of biomedical materials research. Part A Ma, T., Ren, P., Larsen, D. M., Suenaga, E., Zilber, S., Genovese, M., Smith, R. L., Goodman, S. B. 2009; 89 (1): 117-123

  Abstract

  The inhibitor of p38 mitogen-activated protein kinase (MAPK) is of interest in the nonoperative treatment of periprosthetic osteolysis due to wear particles. Previous studies demonstrated that an oral p38 MAPK inhibitor did not suppress bone formation when given during the initial phase of tissue differentiation. However, the oral p38 MAPK inhibitor also did not curtail the foreign body and chronic inflammatory response to particles when given simultaneously. The purpose of the current study was to examine the efficacy of a p38 MAPK inhibitor, SCIO-323, on mitigating an established inflammatory reaction that parallels the clinical situation more closely. The Bone Harvest Chamber was implanted in rabbits and submicron polyethylene particles were placed in the chamber for 6 weeks. The contents of the chambers were harvested every 6 weeks. Oral treatment with the SCIO-323 included delivery for 3 weeks and stopping for 3 weeks, delivery for 3 weeks after an initial 3-week delay, and delivery for 6 weeks continuously. Administration of the SCIO-323 continuously for 6 weeks with/without the presence of particles, or for the initial 3 of 6 weeks had minor effects on bone ingrowth. After establishing a particle-induced chronic inflammatory reaction for 3 weeks, administration of SCIO-323 for a subsequent 3 weeks suppressed net bone formation. The activity of osteoclast-like cells remained low among all treatments when compared with the first control. Using the present model, the oral p38 MAPK inhibitor was ineffective in improving bone ingrowth in the presence of polyethylene particles.

  View details for DOI 10.1002/jbm.a.31957

  View details for PubMedID 18431764

• Porous Tantalum in Hip and Knee Reconstructive Surgery JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Patil, N., Lee, K., Goodman, S. B. 2009; 89B (1): 242-251

  Abstract

  Conventional porous-coated joint prostheses used in hip and knee reconstruction have demonstrated good clinical results, however, these implants possess some inherent shortcomings such as low volumetric porosity, suboptimal frictional characteristics, and higher modulus of elasticity relative to that of bone. Porous tantalum, a novel porous biomaterial was developed to address these limitations. Extensive laboratory studies have revealed that porous tantalum has physical, mechanical and tissue in growth properties that makes it a potentially improved biomaterial particularly in complex joint reconstructions. Porous tantalum is a highly porous biomaterial with good biocompatibility, excellent corrosion resistance, and high coefficient of friction. The short term clinical results of porous tantalum in primary hip, revision hip, and knee reconstructive surgery are encouraging but further studies will be needed to determine whether the theoretical advantages of porous tantalum can provide long term biological fixation and stability. This review presents the biomaterial properties and clinical results of porous tantalum devices in hip and knee reconstructive surgeries.

  View details for DOI 10.1002/jbm.b.31198

  View details for Web of Science ID 000264460200028

• Ultrahigh molecular weight polyethylene wear debris inhibits osteoprogenitor proliferation and differentiation in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2009; 89A (1): 242-247

  Abstract

  Polyethylene wear debris induces progressive osteolysis by increasing bone degradation and suppressing bone formation. Polyethylene particles inhibit the function of mature osteoblasts, but whether polyethylene particles also interfere with the proliferation and differentiation of osteoprogenitor cells is unknown. In this study, we investigated the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on the osteogenic activity of primary murine bone marrow osteoprogenitors and MC3T3-E1 preosteoblastic cells in vitro. Submicron-sized UHMWPE particles generated from wear simulator tests were isolated from serum-containing solution by density gradient centrifugation. The particles were coated onto the surface of culture wells at concentrations of 0.038, 0.075, 0.150, 0.300, and 0.600% v/v in a layer of type I collagen matrix. Primary murine bone marrow cells and MC3T3-E1 preosteoblasts were seeded onto the particle-collagen matrix and induced to differentiate in osteogenic medium for 20 days. Exposure of both cell populations to UHMWPE particles resulted in a dose-dependent decrease in mineralization, proliferation, alkaline phosphatase activity, and osteocalcin production when compared with control cells cultured on collagen matrix without particles. Complete suppression of osteogenesis was observed at particle concentrations > or =0.150% v/v. This study demonstrated that UHMWPE particles inhibit the osteogenic activity of osteoprogenitor cells, which may result in reduced periprosthetic bone regeneration and repair.

  View details for DOI 10.1002/jbm.a.32001

  View details for Web of Science ID 000263981300024

• Cell Therapy for Bone Regeneration-Bench to Bedside JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Lee, K., Chan, C. K., Patil, N., Goodman, S. B. 2009; 89B (1): 252-263

  Abstract

  The concept of bone tissue engineering, which began in the early 1980s, has seen tremendous growth in the numbers of research studies. One of the key areas of research has been in the field of mesenchymal stem cells, where the challenge is to produce the perfect tissue-engineered bone construct. This practical review summarizes basic and applied state-of-the-art research in the area of mesenchymal stem cells, and highlights the important translational research that has already been initiated. The topics that will be covered include the sources of stem cells in use, scaffolds, gene therapy, clinical applications in nonunions, tumors, osteonecrosis, revision arthroplasties, and spine fusion. Although significant challenges remain, there exists an exceptional opportunity to translate basic research in mesenchymal stem cell technologies into viable clinical treatments for bone regeneration.

  View details for DOI 10.1002/jbm.b.31199

  View details for Web of Science ID 000264460200029

• Efficacy of a p38 mitogen activated protein kinase inhibitor in mitigating an established inflammatory reaction to polyethylene particles in vivo JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Ma, T., Ren, P., Larsen, D. M., Suenaga, E., Zilber, S., Genovese, M., Smith, R. L., Goodman, S. B. 2009; 89A (1): 117-123

  Abstract

  The inhibitor of p38 mitogen-activated protein kinase (MAPK) is of interest in the nonoperative treatment of periprosthetic osteolysis due to wear particles. Previous studies demonstrated that an oral p38 MAPK inhibitor did not suppress bone formation when given during the initial phase of tissue differentiation. However, the oral p38 MAPK inhibitor also did not curtail the foreign body and chronic inflammatory response to particles when given simultaneously. The purpose of the current study was to examine the efficacy of a p38 MAPK inhibitor, SCIO-323, on mitigating an established inflammatory reaction that parallels the clinical situation more closely. The Bone Harvest Chamber was implanted in rabbits and submicron polyethylene particles were placed in the chamber for 6 weeks. The contents of the chambers were harvested every 6 weeks. Oral treatment with the SCIO-323 included delivery for 3 weeks and stopping for 3 weeks, delivery for 3 weeks after an initial 3-week delay, and delivery for 6 weeks continuously. Administration of the SCIO-323 continuously for 6 weeks with/without the presence of particles, or for the initial 3 of 6 weeks had minor effects on bone ingrowth. After establishing a particle-induced chronic inflammatory reaction for 3 weeks, administration of SCIO-323 for a subsequent 3 weeks suppressed net bone formation. The activity of osteoclast-like cells remained low among all treatments when compared with the first control. Using the present model, the oral p38 MAPK inhibitor was ineffective in improving bone ingrowth in the presence of polyethylene particles.

  View details for DOI 10.1002/jbm.a.31957

  View details for Web of Science ID 000263981300011

• Porous tantalum in hip and knee reconstructive surgery. Journal of biomedical materials research. Part B, Applied biomaterials Patil, N., Lee, K., Goodman, S. B. 2009; 89 (1): 242-251

  Abstract

  Conventional porous-coated joint prostheses used in hip and knee reconstruction have demonstrated good clinical results, however, these implants possess some inherent shortcomings such as low volumetric porosity, suboptimal frictional characteristics, and higher modulus of elasticity relative to that of bone. Porous tantalum, a novel porous biomaterial was developed to address these limitations. Extensive laboratory studies have revealed that porous tantalum has physical, mechanical and tissue in growth properties that makes it a potentially improved biomaterial particularly in complex joint reconstructions. Porous tantalum is a highly porous biomaterial with good biocompatibility, excellent corrosion resistance, and high coefficient of friction. The short term clinical results of porous tantalum in primary hip, revision hip, and knee reconstructive surgery are encouraging but further studies will be needed to determine whether the theoretical advantages of porous tantalum can provide long term biological fixation and stability. This review presents the biomaterial properties and clinical results of porous tantalum devices in hip and knee reconstructive surgeries.

  View details for DOI 10.1002/jbm.b.31198

  View details for PubMedID 18837451

• Cell therapy for bone regeneration--bench to bedside. Journal of biomedical materials research. Part B, Applied biomaterials Lee, K., Chan, C. K., Patil, N., Goodman, S. B. 2009; 89 (1): 252-263

  Abstract

  The concept of bone tissue engineering, which began in the early 1980s, has seen tremendous growth in the numbers of research studies. One of the key areas of research has been in the field of mesenchymal stem cells, where the challenge is to produce the perfect tissue-engineered bone construct. This practical review summarizes basic and applied state-of-the-art research in the area of mesenchymal stem cells, and highlights the important translational research that has already been initiated. The topics that will be covered include the sources of stem cells in use, scaffolds, gene therapy, clinical applications in nonunions, tumors, osteonecrosis, revision arthroplasties, and spine fusion. Although significant challenges remain, there exists an exceptional opportunity to translate basic research in mesenchymal stem cell technologies into viable clinical treatments for bone regeneration.

  View details for DOI 10.1002/jbm.b.31199

  View details for PubMedID 18777578

• Ultrahigh molecular weight polyethylene wear debris inhibits osteoprogenitor proliferation and differentiation in vitro. Journal of biomedical materials research. Part A Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2009; 89 (1): 242-247

  Abstract

  Polyethylene wear debris induces progressive osteolysis by increasing bone degradation and suppressing bone formation. Polyethylene particles inhibit the function of mature osteoblasts, but whether polyethylene particles also interfere with the proliferation and differentiation of osteoprogenitor cells is unknown. In this study, we investigated the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on the osteogenic activity of primary murine bone marrow osteoprogenitors and MC3T3-E1 preosteoblastic cells in vitro. Submicron-sized UHMWPE particles generated from wear simulator tests were isolated from serum-containing solution by density gradient centrifugation. The particles were coated onto the surface of culture wells at concentrations of 0.038, 0.075, 0.150, 0.300, and 0.600% v/v in a layer of type I collagen matrix. Primary murine bone marrow cells and MC3T3-E1 preosteoblasts were seeded onto the particle-collagen matrix and induced to differentiate in osteogenic medium for 20 days. Exposure of both cell populations to UHMWPE particles resulted in a dose-dependent decrease in mineralization, proliferation, alkaline phosphatase activity, and osteocalcin production when compared with control cells cultured on collagen matrix without particles. Complete suppression of osteogenesis was observed at particle concentrations > or =0.150% v/v. This study demonstrated that UHMWPE particles inhibit the osteogenic activity of osteoprogenitor cells, which may result in reduced periprosthetic bone regeneration and repair.

  View details for DOI 10.1002/jbm.a.32001

  View details for PubMedID 18442106

• Increased Expression of Toll-like Receptors in Aseptic Loose Periprosthetic Tissues and Septic Synovial Membranes Around Total Hip Implants JOURNAL OF RHEUMATOLOGY Tamaki, Y., Takakubo, Y., Goto, K., Hirayama, T., Sasaki, K., Konttinen, Y. T., Goodman, S. B., Takagi, M. 2009; 36 (3): 598-608

  Abstract

  Toll-like receptors (TLR) are transmembrane proteins found in various cells. They recognize infectious and endogenous threats, so-called danger signals, that evoke inflammation and assist adaptive immune reactions. It has been suggested that TLR play a role in periprosthetic tissues and arthritic synovium. Our objective was to elucidate tissue localization and functional roles of TLR in periprosthetic tissues in 2 different pathologic conditions, aseptic and septic implant loosening.For immunohistochemistry studies, aseptic synovial-like membranes of periprosthetic connective tissues (n = 15) and septic synovial capsular tissues (n = 5) were obtained at revision surgery and from salvage of infected totally replaced hips, respectively. Osteoarthritic synovial tissues were used for comparison (n = 5). Samples were processed for immunohistopathologic analyses for tissue colocalization of TLR with CD68 and/or CD15 using the Alexa fluorescent system. Total RNA was isolated from frozen tissues and converted into cDNA, TLR 2, 4, 5 and 9 sequences were amplified, and the products were quantified using real-time polymerase chain reaction.Immunofluorescent staining showed colocalization of TLR 2, 4, 5, and 9 with CD68 in the focal monocyte/macrophage aggregates in aseptic synovial-like membranes from loose total hip replacements. TLR 2, 4, 5, and 9 were also found colocalized with CD15+ polymorphonuclear leukocytes and CD68+ mononuclear cells of the synovial membranes from septic total hip replacements. In osteoarthritic synovial tissues, expression of TLR was found only in vascular cells and mononuclear cells, and the reactivity was weak. mRNA levels of TLR 2, 4, 5, and 9 were increased in both aseptic and septic periprosthetic tissues. TLR 2 and 5 were significantly higher than TLR 4 and 9 in aseptic and septic samples.Peri-implant tissues were well equipped with TLR in both aseptic and septic conditions. TLR 2- and TLR 5-mediated responses seemed to dominate. In aseptic loosening, monocytes/ macrophages were the main TLR-equipped cells apparently responsible for alarmin-induced responses. This could lead to production of inflammatory cytokines and extracellular matrix-degrading proteinases after phagocytosis of wear debris derived from an implant, but in septic cases they eventually respond to microbial components. Thus, inflammatory cells in both aseptic and septic tissues were equipped with TLR, providing them with responsiveness to both endogenous and exogenous TLR ligands.

  View details for DOI 10.3899/jrheum.080390

  View details for Web of Science ID 000263940000022

  View details for PubMedID 19208601

• Stem Cell-Mediated Accelerated Bone Healing Observed with in Vivo Molecular and Small Animal Imaging Technologies in a Model of Skeletal Injury JOURNAL OF ORTHOPAEDIC RESEARCH Lee, S., Padmanabhan, P., Ray, P., Gambhir, S. S., Doyle, T., Contag, C., Goodman, S. B., Biswal, S. 2009; 27 (3): 295-302

  Abstract

  Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [(18)F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [(18)F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC's traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p < 0.05). Systemically administered ADMC's traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route.

  View details for DOI 10.1002/jor.20736

  View details for PubMedID 18752273

• The Accuracy of Preoperative Templating in Cementless Total Hip Arthroplasty JOURNAL OF ARTHROPLASTY Unnanuntana, A., Wagner, D., Goodman, S. B. 2009; 24 (2): 180-186

  Abstract

  We evaluated the accuracy and clinical usefulness of preoperative templating in 109 cementless total hip arthroplasties. The size of the prosthesis was exactly predicted in 46 (42.2%) acetabular and 75 (68.8%) femoral components. The accuracy increased to greater than 90% if the prosthesis size was within 1 or 2 sizes (above or below) for femoral component and acetabular components, respectively. Having a contralateral total hip arthroplasty as a guide for preoperative templating was associated with greater accuracy in predicting the femoral component size only. Eighty-eight percent of the acetabular components were oriented inside the presumed safe range for inclination; 42% of the acetabular components were in the presumed safe range of anteversion. The mean postoperative leg length discrepancy was 0.9 +/- 6.8 mm; 93.5% had a discrepancy within 10 mm.

  View details for DOI 10.1016/j.arth.2007.10.032

  View details for PubMedID 18534455

• Outcome and Complications of Constrained Acetabular Components ORTHOPEDICS Yang, C., Goodman, S. B. 2009; 32 (2): 115-123

  Abstract

  Constrained acetabular liners were developed for the surgical treatment of recurrent instability by holding the femoral head captive within the socket. This article summarizes the data describing constrained component designs, indications, outcome, and complications. Different designs accept head sizes of varying diameter and have differing amounts of rim elevation and offset, allowing slight variations in the range of movement allowed. Complications of constrained acetabular components can be divided into three categories. The first category is directly related to the constraining mechanism such as dislocation, head dissociation from the stem, liner dissociation from the acetabular device, and impingement with or without locking ring breakage. The second category is related to increased constraint such as aseptic component loosening and osteolysis and periprosthetic fracture. The third category includes those cases not associated with increased constraint such as infection, deep vein thrombosis, and periprosthetic fracture. This device is effective at achieving hip stability, but the complications related to the constraining mechanism and increased constraint are of concern. These devices should be used as a salvage measure for the treatment of severe instability.

  View details for Web of Science ID 000263770300006

  View details for PubMedID 19301794

• Cell Therapy for Secondary Osteonecrosis of the Femoral Condyles Using the Cellect DBM System A Preliminary Report JOURNAL OF ARTHROPLASTY Lee, K., Goodman, S. B. 2009; 24 (1): 43-48

  Abstract

  We describe a novel treatment of secondary osteonecrosis (ON) of the femoral condyles that is relatively simple, has low morbidity, and does not preclude the patient from other more extensive treatments in the event of failure. Three patients with extensive secondary ON of the femoral condyles were treated with decompression and debridement of the area of ON and grafting with the Cellect DBM System (Depuy Spine, Inc., Raynham, Mass), which provided a graft matrix enriched with a 3-fold to 4-fold increase in osteoprogenitor cells. At 2 years, all 3 patients had no complications and had excellent results with near-normal function and activity levels. Our preliminary results demonstrate that this technique is a viable option, at least in the short term, especially in patients with extensive, multifocal lesions.

  View details for DOI 10.1016/j.arth.2008.01.133

  View details for Web of Science ID 000262236700008

  View details for PubMedID 18534437

• In Vivo Murine Model of Continuous Intramedullary Infusion of Particles-A Preliminary Study JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Ma, T., Ortiz, S. G., Huang, Z., Ren, P., Smith, R. L., Goodman, S. B. 2009; 88B (1): 250-253

  Abstract

  Continued production of wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). However, continuous delivery of clinically relevant particles using a viable, cost effective, quantitative animal model to simulate the scenario in humans has been a challenge for orthopedic researchers. In this study, we successfully infused blue-dyed polystyrene particles, similar in size to wear debris in humans, to the intramedullary space of the mouse femur for 4 weeks using an osmotic pump. Approximately 40% of the original particle load (85 microL) was delivered into the intramedullary space, an estimate of 3 x 10(9) particles. The visible blue dye carried by the particles confirmed the delivery. This model demonstrated that continuous infusion of particles to the murine bone-implant interface is possible. In vivo biological processes associated using wear debris particles can be studied using this new animal model.

  View details for DOI 10.1002/jbm.b.31175

  View details for Web of Science ID 000261895300027

  View details for PubMedCentralID PMC2597706

• In vivo murine model of continuous intramedullary infusion of particles--a preliminary study. Journal of biomedical materials research. Part B, Applied biomaterials Ma, T., Ortiz, S. G., Huang, Z., Ren, P., Smith, R. L., Goodman, S. B. 2009; 88 (1): 250-253

  Abstract

  Continued production of wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). However, continuous delivery of clinically relevant particles using a viable, cost effective, quantitative animal model to simulate the scenario in humans has been a challenge for orthopedic researchers. In this study, we successfully infused blue-dyed polystyrene particles, similar in size to wear debris in humans, to the intramedullary space of the mouse femur for 4 weeks using an osmotic pump. Approximately 40% of the original particle load (85 microL) was delivered into the intramedullary space, an estimate of 3 x 10(9) particles. The visible blue dye carried by the particles confirmed the delivery. This model demonstrated that continuous infusion of particles to the murine bone-implant interface is possible. In vivo biological processes associated using wear debris particles can be studied using this new animal model.

  View details for DOI 10.1002/jbm.b.31175

  View details for PubMedID 18777575

• Systemic trafficking of macrophages induced by bone cement particles in nude mice BIOMATERIALS Ren, P., Lee, S., Biswal, S., Goodman, S. B. 2008; 29 (36): 4760-4765

  Abstract

  Macrophages play an important role in the biological response to wear particles, which can result in periprosthetic osteolysis and implant loosening. In this study, we demonstrate that polymer particles induce systemic trafficking of macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 10% (w/v) Simplex bone cement (BC) suspensions or saline (PBS). Reporter RAW264.7 macrophages which stably expressed the bioluminescent reporter gene fluc, and the fluorescence reporter gene gfp, were injected intravenously. Bioluminescence imaging was performed immediately and periodically at 2-day intervals until day 14. Compared to the non-operated contralateral femora, the bioluminescent signal of femora injected with BC suspension increased 4.7+/-1.6 and 7.8+/-2.9-fold at day 6 and 8, respectively. The same values for PBS group were 1.2+/-0.2 and 1.4+/-0.5, respectively. The increase of bioluminescence of the BC group was significantly greater than the PBS group at day 8 (p<0.05) and day 6 (p<0.1). Histological study confirmed the presence of reporter macrophages within the medullary canal of mice that received cement particles. Modulation of the signaling mechanisms that regulate systemic macrophage trafficking may provide a new strategy for mitigating the chronic inflammatory response and osteolysis associated with wear debris.

  View details for DOI 10.1016/j.biomaterials.2008.09.004

  View details for PubMedID 18824259

• New Bone Formation by Murine Osteoprogenitor Cells Cultured on Corticocancellous Allograft Bone JOURNAL OF ORTHOPAEDIC RESEARCH Nelson, E. R., Huang, Z., Ma, T., Lindsey, D., Jacobs, C., Smith, R. L., Goodman, S. B. 2008; 26 (12): 1660-1664

  Abstract

  The gold standard for bone grafting in orthopedics is autograft, however autograft has a limited supply and is associated with significant morbidity at the harvest site. One alternative, allograft bone, provides an osteoconductive scaffold, is in less limited supply, and it does not require a harvest from the patient. However, allograft lacks both osteogenic cells and osteoinductive proteins that make autograft bone so advantageous. This study provides a model to investigate strategies for augmentation of corticocancellous allograft bone discs with bone marrow-derived osteoprogenitor cells (OPCs) plus exogenous growth factors in vitro. In this model, allograft bone discs were created by cutting 1-mm thick slices from the distal femur and proximal tibia of euthanized mice. The allografts were sterilized and scanned by micro-computed tomography (microCT) to provide the pre-culture graft volume and trabecular characteristics. The discs were then seeded with OPCs harvested from murine bone marrow. The seeded grafts were placed in organ culture until harvest, after which they were re-scanned by microCT and the data compared to the corresponding pre-culture data. In addition, bone morphogenetic protein-7 (BMP-7, also know as osteogenic protein-1 or OP-1), basic fibroblast growth factor (bFGF), and OP-1 combined with bFGF were added on a daily basis to the cultures. After final microCT scanning, all grafts were sectioned and evaluated histologically after hematoxylin and eosin (H&E) staining. microCT scans of cultured allografts with cells at 3, 5, and 9 weeks showed a time-dependent, statistically significant increase in bone volume. The trabecular thickness (Tb.Th.) of grafts, from both groups that were augmented with OP-1, showed a statistically significant increase in trabecular thickness of allografts with OPCs. These data suggest that bone marrow-derived OPCs adhere to, and produce, new bone on corticocancellous allograft in vitro. When exogenous OP-1 is added to this model, an increase in the production of bone onto the corticocancellous allograft bone disc is seen. This model allows for the investigation of the effects of multiple growth factors, and other interventions, on OPCs seeded onto allograft bone in vitro.

  View details for DOI 10.1002/jor.20676

  View details for PubMedID 18524004

• Effect of Nanofiber-Coated Surfaces on the Proliferation and Differentiation of Osteoprogenitors In Vitro TISSUE ENGINEERING PART A Huang, Z., Daniels, R. H., Enzerink, R., Hardev, V., Sahi, V., Goodman, S. B. 2008; 14 (11): 1853-1859

  Abstract

  The osteoconductive property of titanium (Ti) surfaces is important in orthopedic and dental implant devices. Surface modifications of Ti have been proposed to further improve osseointegration. In this study, three different materials, silicon (Si), silicon oxide (SiO(2)), and titanium oxide (TiO(2)), were used to construct nanofibers for surface coating of Ti alloy Ti-6Al-4 V (Ti alloy). MC3T3-E1 osteoprogenitor cells were seeded on nanofiber-coated discs and cultured for 42 days. DNA, alkaline phosphatase, osteocalcin, and mineralization nodules were measured using PicoGreen, enzyme-linked immunosorbent assay, and calcein blue staining to detect the attachment, proliferation, differentiation, and mineralization of MC3T3-E1 cells, respectively. The results demonstrated that the initial cell attachments on nanofiber-coated discs were significantly lower, although cell proliferation on Si and SiO(2) nanofiber-coated discs was better than on Ti alloy surfaces. TiO(2) nanofibers facilitated a higher cellular differentiation capacity than Ti alloy and tissue culture-treated polystyrene surfaces. Thus, surface modification using nanofibers of various materials can alter the attachment, proliferation, and differentiation of osteoprogenitor cells in vitro.

  View details for DOI 10.1089/ten.tea.2007.0399

  View details for PubMedID 18950272

• Continuous Intramedullary Polymer Particle Infusion Using a Murine Femoral Explant Model JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Ortiz, S. G., Ma, T., Regula, D., Smith, R. L., Goodman, S. B. 2008; 87B (2): 440-446

  Abstract

  In vitro models are important investigative tools in understanding the biological processes involved in wear-particle-induced chronic inflammation and periprosthetic osteolysis. In the clinical scenario, particles are produced and delivered continuously over extended periods of time. Previously, we quantified the delivery of both polystyrene and polyethylene particles over 2- and 4-week time periods using osmotic pumps and collection tubes. In the present study, we used explanted mice femora in organ culture and showed that continuous intramedullary delivery of submicron-sized polymer particles using osmotic pumps is feasible. Furthermore, infusion of 2.60 x 10(11) particles per mL (intermediate concentration) of ultrahigh molecular weight polyethylene (UHMWPE) for 2 weeks and 8.06 x 10(11) particles per mL (high concentration) UHMWPE for 4 weeks both yielded significantly higher scores for bone loss when compared with controls in which only mouse serum was infused.

  View details for DOI 10.1002/jbm.b.31122

  View details for Web of Science ID 000260355000017

• Continuous intramedullary polymer particle infusion using a murine femoral explant model. Journal of biomedical materials research. Part B, Applied biomaterials Ortiz, S. G., Ma, T., Regula, D., Smith, R. L., Goodman, S. B. 2008; 87 (2): 440-446

  Abstract

  In vitro models are important investigative tools in understanding the biological processes involved in wear-particle-induced chronic inflammation and periprosthetic osteolysis. In the clinical scenario, particles are produced and delivered continuously over extended periods of time. Previously, we quantified the delivery of both polystyrene and polyethylene particles over 2- and 4-week time periods using osmotic pumps and collection tubes. In the present study, we used explanted mice femora in organ culture and showed that continuous intramedullary delivery of submicron-sized polymer particles using osmotic pumps is feasible. Furthermore, infusion of 2.60 x 10(11) particles per mL (intermediate concentration) of ultrahigh molecular weight polyethylene (UHMWPE) for 2 weeks and 8.06 x 10(11) particles per mL (high concentration) UHMWPE for 4 weeks both yielded significantly higher scores for bone loss when compared with controls in which only mouse serum was infused.

  View details for DOI 10.1002/jbm.b.31122

  View details for PubMedID 18536041

• Averaging different alignment axes improves femoral rotational alignment in computer-navigated total knee arthroplasty. journal of bone and joint surgery. American volume Siston, R. A., Cromie, M. J., Gold, G. E., Goodman, S. B., Delp, S. L., Maloney, W. J., Giori, N. J. 2008; 90 (10): 2098-2104

  Abstract

  Computer navigation systems generally establish the rotational alignment axis of the femoral component on the basis of user-defined anatomic landmarks. However, navigation systems can also record knee kinematics and average alignment axes established with multiple techniques. We hypothesized that establishing femoral rotational alignment with the use of kinematic techniques is more accurate and precise (repeatable) than the use of anatomic techniques and that establishing femoral rotational alignment by averaging the results of different alignment techniques is more accurate and precise than the use of a single technique.Twelve orthopaedic surgeons used three anatomic and two kinematic alignment techniques to establish femoral rotational alignment axes in a series of nine cadaver knees. The axes derived with the individual anatomic and kinematic techniques as well as the axes derived with six combination techniques--i.e., those involving averaging of the alignments established with two of the individual techniques--were compared against a reference axis established with computed tomography images of each femur.The kinematic methods were not more accurate (did not have smaller mean errors) or more precise (repeatable) than the anatomic techniques. The combination techniques were accurate (five of the six had a mean error of <5 degrees ) and significantly more precise than all but one of the single methods. The percentage of measurements with <5 degrees of error as compared with the reference epicondylar axis was 37% for the individual anatomic techniques, 30% for the individual kinematic techniques, and 58% for the combination techniques.Averaging the results of kinematic and anatomic techniques, which is possible with computer navigation systems, appears to improve the accuracy of rotational alignment of the femoral component. The number of rotational alignment outliers was reduced when combination techniques were used; however, they are still a problem and continued improvement in methods to accurately establish rotation of the femoral component in total knee arthroplasty is needed.

  View details for DOI 10.2106/JBJS.G.00996

  View details for PubMedID 18829906

• Averaging Different Alignment Axes Improves Femoral Rotational Alignment in Computer-Navigated Total Knee Arthroplasty JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Siston, R. A., Cromie, M. J., Gold, G. E., Goodman, S. B., Delp, S. L., Maloney, W. J., Giori, N. J. 2008; 90A (10): 2098-2104

  Abstract

  Computer navigation systems generally establish the rotational alignment axis of the femoral component on the basis of user-defined anatomic landmarks. However, navigation systems can also record knee kinematics and average alignment axes established with multiple techniques. We hypothesized that establishing femoral rotational alignment with the use of kinematic techniques is more accurate and precise (repeatable) than the use of anatomic techniques and that establishing femoral rotational alignment by averaging the results of different alignment techniques is more accurate and precise than the use of a single technique.Twelve orthopaedic surgeons used three anatomic and two kinematic alignment techniques to establish femoral rotational alignment axes in a series of nine cadaver knees. The axes derived with the individual anatomic and kinematic techniques as well as the axes derived with six combination techniques--i.e., those involving averaging of the alignments established with two of the individual techniques--were compared against a reference axis established with computed tomography images of each femur.The kinematic methods were not more accurate (did not have smaller mean errors) or more precise (repeatable) than the anatomic techniques. The combination techniques were accurate (five of the six had a mean error of <5 degrees ) and significantly more precise than all but one of the single methods. The percentage of measurements with <5 degrees of error as compared with the reference epicondylar axis was 37% for the individual anatomic techniques, 30% for the individual kinematic techniques, and 58% for the combination techniques.Averaging the results of kinematic and anatomic techniques, which is possible with computer navigation systems, appears to improve the accuracy of rotational alignment of the femoral component. The number of rotational alignment outliers was reduced when combination techniques were used; however, they are still a problem and continued improvement in methods to accurately establish rotation of the femoral component in total knee arthroplasty is needed.

  View details for DOI 10.2106/JBJS.G.00996

  View details for Web of Science ID 000259873300006

• Conversion total hip replacement after malunited intertrochanteric fracture: a technical note. American journal of orthopedics (Belle Mead, N.J.) Unnanuntana, A., Goodman, S. B. 2008; 37 (10): 506-509

  Abstract

  Malunited intertrochanteric fracture involves anatomical changes such as medialization of the femoral canal and intramedullary remodeling and sclerosis. These changes introduce difficulties that are not ordinarily encountered with routine total hip replacement. Possible intraoperative complications include spiral femoral fracture during hip dislocation and failure to identify the femoral canal. Therefore, recognizing the anatomical changes before and during surgery is crucial. In this article, we describe specific surgical steps and techniques by which these problems may be avoided, thus minimizing potential complications.

  View details for PubMedID 19081877

• An in vivo murine model of continuous intramedullary infusion of polyethylene particles BIOMATERIALS Ma, T., Huang, Z., Ren, P., McCally, R., Lindsey, D., Smith, R. L., Goodman, S. B. 2008; 29 (27): 3738-3742

  Abstract

  Wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). To study the complex cascade associated with the continuous generation of particles, a robust animal model is essential. To date, an animal model that incorporates continuously delivered particles to an intramedullary orthopaedic implant has not been available. In this study, we successfully infused clinically relevant ultra high molecular weight polyethylene particles, previously isolated from joint simulator tests, to the intramedullary space of the mouse femur for 4 weeks using a subcutaneous osmotic pump. Reduction of bone volume following the 4-week infusion of UHMWPE was detected by microCT. UHMWPE particles also changed the level of Alkaline Phosphatase expression in the infused femurs. Continuous infusion of particles to the murine bone-implant interface simulated the clinical scenario of local polymer wear particle generation and delivery in humans and can be used to further study the biological processes associated with wear debris particles.

  View details for DOI 10.1016/j.biomaterials.2008.05.031

  View details for PubMedID 18561997

• Controlled release of growth factors on allograft bone in vitro 5th Musculoskeletal Transplant Foundation Symposium Huang, Z., Ryu, W., Ren, P., Fasching, R., Goodman, S. B. SPRINGER. 2008: 1905–11

  Abstract

  Allografts are important alternatives to autografts for treating defects after major bone loss. Bone growth factors have both local autocrine and paracrine effects and regulate the growth, proliferation, and differentiation of osteoprogenitor cells. To study the effects of prolonged, continuous, local delivery of growth factors on bone growth, we developed a new microelectromechanical system (MEMS) drug delivery device. Bone marrow cells from mice were seeded on mouse allograft discs and cultured in osteogenic media with osteogenic protein 1 (OP-1) and/or basic fibroblast growth factor (FGF-2) delivered from MEMS devices for 6 weeks. We monitored bone formation by changes of bone volume using micro-CT scanning and release of osteocalcin using ELISA. The data suggest the MEMS devices delivered constant concentrations of OP-1 and FGF-2 to the media. Bone marrow cells grew on the allografts and increased bone volume. Addition of OP-1 increased bone formation whereas FGF-2 decreased bone formation. Local delivery of growth factors over a prolonged period modulated the differentiation of osteoprogenitor cells on allograft bone.

  View details for DOI 10.1007/s11999-008-0290-8

  View details for PubMedID 18509711

• Polymethylmethacrylate particles inhibit osteoblastic differentiation of MC3T3-E1 osteoprogenitor cells JOURNAL OF ORTHOPAEDIC RESEARCH Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2008; 26 (7): 932-936

  Abstract

  Orthopedic wear debris has been implicated as a significant inhibitory factor of osteoblast differentiation. Polymethylmethacrylate (PMMA) particles have been previously shown to inhibit the differentiation of osteoprogenitors in heterogeneous murine marrow stromal cell cultures, but the effect of PMMA particles on pure osteoprogenitor populations remains unknown. In this study, we challenged murine MC3T3-E1 osteoprogenitor cells with PMMA particles during their initial differentiation in osteogenic medium. MC3T3-E1 cultures challenged with PMMA particles showed a gradual dose-dependent decrease in mineralization, cell number, and alkaline phosphatase activity at low particle doses (0.038-0.150% v/v) and complete reduction of these outcome parameters at high particle doses (> or =0.300% v/v). MC3T3-E1 cultures challenged with a high particle dose (0.300% v/v) showed no rise in these outcome parameters over time, whereas cultures challenged with a low particle dose (0.075% v/v) showed a normal or reduced rate of increase compared to controls. Osteocalcin production was not significantly affected by particles at all doses tested. MC3T3-E1 cells grown in conditioned medium from particle-treated MC3T3-E1 cultures showed a significant reduction in mineralization only. These results indicate that direct exposure of MC3T3-E1 osteoprogenitors to PMMA particles results in suppression of osteogenic proliferation and differentiation.

  View details for DOI 10.1002/jor.20618

  View details for PubMedID 18302244

• Current state and future of joint replacements in the hip and knee EXPERT REVIEW OF MEDICAL DEVICES Lee, K., Goodman, S. B. 2008; 5 (3): 383-393

  Abstract

  Joint replacements of the hip and knee are among the most clinically successful operations. According to figures compiled by the American Academy of Orthopaedic Surgeons, the number of primary total hip replacements performed in the USA was 220,000 in 2003. This was 38% more than in 1996 and this number is expected to rise to 572,000 (plus another 97,000 revisions) by 2030. The number of primary total knee replacements performed in 2003 was approximately 418,000 and is expected to rise exponentially with the increasing numbers of baby boomers and the aging population. Current research focuses not only on extending implant longevity, but also on improving function to meet the increased demands of today's patients, who are likely to be younger and more active than their predecessors two decades ago. Potential advancements in arthroplasty surgery include new, more wear-resistant bearing surfaces, porous metals to enhance osseointegration and replace lost bone stock, a clearer understanding of the biological processes associated with periprosthetic osteolysis, minimally invasive surgery and computer assisted surgery. Long-term studies are needed to establish the efficacy of these new technologies.

  View details for DOI 10.1586/17434440-5.3-383

  View details for PubMedID 18452388

• Quantitation of bone area in undecalcified frozen sections with fluorescent microscopy JOURNAL OF HISTOTECHNOLOGY Ren, P., Ma, T., Huang, Z., Smith, R. L., Goodman, S. B. 2008; 31 (1): 15-17

  View details for Web of Science ID 000258533800002

• Histomorphometric analysis of the intramedullary bone response to titanium particles in wild-type and IL-1R1 knock-out mice: a preliminary study. Journal of biomedical materials research. Part B, Applied biomaterials Bragg, B., Epstein, N. J., Ma, T., Goodman, S., Smith, R. L. 2008; 84 (2): 559-570

  Abstract

  Aseptic loosening of implants following total joint arthroplasty remains a major cause of implant failure. Particulate debris generated primarily from wear results in inflammatory mediated periprosthetic osteolysis. Titanium is a commonly utilized metal in joint arthroplasty and titanium debris induces the production of the pro-inflammatory cytokine IL-1. To further elucidate the role of IL-1, this study examined the response of murine femora to the presence of titanium particles following implantation of an intramedullary rod in mice lacking the receptor for IL-1. We hypothesized that the inflammatory effects of wear debris on bone would be mitigated in IL-1R1 deficient mice with a resultant decrease in resorption. Femora receiving titanium particles demonstrated a marked inflammatory response in wild-type mice with increased endocortical resorption, periprosthetic membrane formation, and significant histomorphometric changes. Femora exposed to titanium particles in the knockout mice also demonstrated osteolysis with irregular deposition of trabecular bone and increased cortical porosity. The persistence of inflammation and osteolysis, despite the lack of functional IL-1R1, suggests a multi-factorial role for IL-1 in the proinflammatory cascade resulting from wear debris. This intramedullary murine model provides the ability to evaluate and quantify the proinflammatory cascade in an in vivo model approximating prosthesis failure.

  View details for PubMedID 17618512

• Histomorphometric Analysis of the intramedullary bone response to titanium particles in wild-type and IL-1R1 knowk-out mice: A preliminary study JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Bragg, B., Epstein, N., Ma, T., Goodman, S., Smith, R. L. 2008; 84B (2): 559-570

  Abstract

  Aseptic loosening of implants following total joint arthroplasty remains a major cause of implant failure. Particulate debris generated primarily from wear results in inflammatory mediated periprosthetic osteolysis. Titanium is a commonly utilized metal in joint arthroplasty and titanium debris induces the production of the pro-inflammatory cytokine IL-1. To further elucidate the role of IL-1, this study examined the response of murine femora to the presence of titanium particles following implantation of an intramedullary rod in mice lacking the receptor for IL-1. We hypothesized that the inflammatory effects of wear debris on bone would be mitigated in IL-1R1 deficient mice with a resultant decrease in resorption. Femora receiving titanium particles demonstrated a marked inflammatory response in wild-type mice with increased endocortical resorption, periprosthetic membrane formation, and significant histomorphometric changes. Femora exposed to titanium particles in the knockout mice also demonstrated osteolysis with irregular deposition of trabecular bone and increased cortical porosity. The persistence of inflammation and osteolysis, despite the lack of functional IL-1R1, suggests a multi-factorial role for IL-1 in the proinflammatory cascade resulting from wear debris. This intramedullary murine model provides the ability to evaluate and quantify the proinflammatory cascade in an in vivo model approximating prosthesis failure.

  View details for DOI 10.1002/jbm.b.30904

  View details for Web of Science ID 000252472900032

• Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Ortiz, S. G., Ma, T., Epstein, N. J., Smith, R. L., Goodman, S. B. 2008; 84B (2): 328-333

  Abstract

  Wear particles produced from total joint replacements have been shown to stimulate a foreign body and chronic inflammatory reaction that results in periprosthetic osteolysis. Most animal models that simulate these events have used a single injection of particles, which is not representative of the clinical scenario, in which particles are continuously generated. The goal of this study was to evaluate the feasibility of an osmotic pump for the continuous delivery of clinically relevant submicron-sized particles over an extended period of time. Blue-dyed polystyrene particles and retrieved ultra-high molecular weight polyethylene (UHMWPE) particles, both suspended in mouse serum, were loaded into an Alzet mini-osmotic pump. Pumps were attached to vinyl tubing that ended with hollow titanium rods, simulating a metal implant, which was suspended in a collection vessel. The number of particles collected was evaluated over 2- and 4-week time periods. Delivery of both the polystyrene and UHMWPE particles was feasible over pump concentrations of 10(9) to 10(11) particles per pump. Furthermore, delivery efficiency of polystyrene particles decreased with increasing initial particle concentration, whereas delivery efficiency of UHMWPE particles increased slightly with increasing initial particle concentration. For UHMWPE, approximately one-third of the particles in the pump were collected at 4 weeks. This in vitro study has quantified the efficiency of a unique particle pumping system that may be used in future in vivo investigations to develop a murine model of continuous particle infusion.

  View details for DOI 10.1002/jbm.b.30875

  View details for Web of Science ID 000252472900003

• Early outcome of a modular femoral component in revision total hip arthroplasty JOURNAL OF ARTHROPLASTY Kang, M. N., Huddleston, J. I., Hwang, K., Imrie, S., Goodman, S. B. 2008; 23 (2): 220-225

  Abstract

  Forty-six hips in 42 patients underwent revision surgery with a modular femoral component (ZMR; Zimmer, Warsaw, Ind). Thirty-nine hips with 2 to 5 years' follow-up were evaluated radiographically and clinically by the Harris hip score and WOMAC pain/stiffness/function scores. The Harris hip score improved from 47.4 to 72.3 (P<.001), with significant improvements in the WOMAC pain/stiffness/function scores. The mean subsidence was 4.4 mm, with 5 hips demonstrating significant subsidence of more than 5 mm. Four hips required reoperation, 1 due to failure of the femoral component. No early complications were encountered regarding the modular junction. Modular, cementless, extensively porous, coated femoral components have demonstrated early clinical and radiographic success. Distal intramedullary fit helps ensure initial stability; proximal modularity further maximizes fit while optimizing hip offset and length.

  View details for DOI 10.1016/j.arth.2007.03.006

  View details for PubMedID 18280416

• Validation and quantification of an in vitro model of continuous infusion of submicron-sized particles. Journal of biomedical materials research. Part B, Applied biomaterials Ortiz, S. G., Ma, T., Epstein, N. J., Smith, R. L., Goodman, S. B. 2008; 84 (2): 328-333

  Abstract

  Wear particles produced from total joint replacements have been shown to stimulate a foreign body and chronic inflammatory reaction that results in periprosthetic osteolysis. Most animal models that simulate these events have used a single injection of particles, which is not representative of the clinical scenario, in which particles are continuously generated. The goal of this study was to evaluate the feasibility of an osmotic pump for the continuous delivery of clinically relevant submicron-sized particles over an extended period of time. Blue-dyed polystyrene particles and retrieved ultra-high molecular weight polyethylene (UHMWPE) particles, both suspended in mouse serum, were loaded into an Alzet mini-osmotic pump. Pumps were attached to vinyl tubing that ended with hollow titanium rods, simulating a metal implant, which was suspended in a collection vessel. The number of particles collected was evaluated over 2- and 4-week time periods. Delivery of both the polystyrene and UHMWPE particles was feasible over pump concentrations of 10(9) to 10(11) particles per pump. Furthermore, delivery efficiency of polystyrene particles decreased with increasing initial particle concentration, whereas delivery efficiency of UHMWPE particles increased slightly with increasing initial particle concentration. For UHMWPE, approximately one-third of the particles in the pump were collected at 4 weeks. This in vitro study has quantified the efficiency of a unique particle pumping system that may be used in future in vivo investigations to develop a murine model of continuous particle infusion.

  View details for PubMedID 17595028

• 2007 AAOS/NIH osteolysis and implant wear: Biological, biomedical engineering, and surgical principles - Introduction JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Gilmour, C. M., Ransford, E. L., Goetz, L., Smith, D., Goodman, S. B., Wright, T. 2008; 16: X-XI

  View details for Web of Science ID 000257474600001

  View details for PubMedID 18612024

• Wear particles and osteolysis ORTHOPAEDIC BONE CEMENTS Patil, N., Goodman, S. B., Deb, S. 2008: 140–64

  View details for DOI 10.1533/9781845695170.1.140

  View details for Web of Science ID 000275832000007

• What is the outcome of treatment for osteolysis? AAOS/NIH Osteolysis and Implant Wear: Biological, Biomedical Engineering, and Surgical Principles Maloney, W., Rosenberg, A. AMER ACAD ORTHOPAEDIC SURGEONS. 2008: S26–S32

  Abstract

  Periprosthetic osteolysis secondary to wear-induced particle generation is a common long-term complication of hip and knee replacement and frequently results in the need for revision surgery. Management of significant bone defects remains a surgical challenge. Surgical intervention must address the wear particle generator (usually, but not always, the bearing surface), the osteolytic defects, and implant-related issues, primarily fixation and alignment. Indications for surgical intervention in the absence of loosening and pain are not well established. In general, patient age and activity level, the location and size of the osteolytic defect, and the clinical record of the implant system will dictate treatment choices.

  View details for PubMedID 18612010

• What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles? Tuan, R. S., Lee, F., Konttinen, Y. T., Wilkinson, J., Smith, R., Implant Wear Symposium 2007 Biolog AMER ACAD ORTHOPAEDIC SURGEONS. 2008: S42–S48

  Abstract

  New clinical and basic science data on the cellular and molecular mechanisms by which wear particles stimulate the host inflammatory response have provided deeper insight into the pathophysiology of periprosthetic bone loss. Interactions among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal stem cells, fibroblasts, endothelial cells, and T cells contribute to the production of pro-inflammatory and pro-osteoclastogenic cytokines such as TNF-alpha, RANKL, M-SCF, PGE2, IL-1, IL-6, and IL-8. These cytokines not only promote osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells. Recent studies indicate that genetic variations in TNF-alpha, IL-1, and FRZB can result in subtle changes in gene function, giving rise to altered susceptibility or severity for periprosthetic inflammation and bone loss. Continuing research on the biologic effects and mechanisms of action of wear particles will provide a rational basis for the development of novel and effective ways of diagnosis, prevention, and treatment of periprosthetic inflammatory bone loss.

  View details for DOI 10.5435/00124635-200800001-00010

  View details for Web of Science ID 000257474600010

  View details for PubMedID 18612013

  View details for PubMedCentralID PMC2714366

• How have alternative bearings (such as metal-on-metal, highly cross-linked polyethylene, and ceramic-on-ceramic) affected the prevention and treatment of osteolysis? AAOS/NIH Osteolysis and Implant Wear: Biological, Biomedical Engineering, and Surgical Principles Callaghan, J. J., Cuckler, J. M., Huddleston, J. I., Galante, J. O. AMER ACAD ORTHOPAEDIC SURGEONS. 2008: S33–S38

  Abstract

  Osteolysis is a multifactorial process dependent on surgical technique, implant design, patient factors, and material composition. Alternative bearing surfaces, such as highly cross-linked polyethylene, ceramic-on-ceramic, and metal-on-metal articular surfaces, have been introduced in an attempt to reduce wear and osteolysis following total hip arthroplasty. Intermediate-term follow-up data available suggest that the prevalence and severity of osteolysis may be reduced with these materials compared with conventional metal-on-polyethylene bearing surface couples. However, long-term data are presently unavailable; the future performance of these bearings awaits clinical validation.

  View details for Web of Science ID 000257474600008

  View details for PubMedID 18612011

• Failure mechanisms in joint replacement JOINT REPLACEMENT TECHNOLOGY Burke, M., Goodman, S., Revell, P. A. 2008: 264–85

  View details for DOI 10.1533/9781845694807.2.264

  View details for Web of Science ID 000276889000013

• Mouse femoral intramedullary injection model: Technique and microCT scan validation JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Zilber, S., Epstein, N., Lee, S., Larsen, M., Ma, T., Smith, R. L., Biswal, S., Goodman, S. B. 2008; 84B (1): 286-290

  Abstract

  The murine femoral intramedullary injection model is frequently used to examine the in vivo effects of biomaterials or cancer cells. The surgical technique includes a knee arthrotomy with patellar dislocation for intramedullary access. This study examined a less invasive surgical approach of direct injection of particles via the transpatellar tendon without patellar dislocation. By using polymethylmethacrylate injection and microCT scan, we found that, compared with the traditional technique, this new approach was more reproducible, less time consuming, and achieved identical volumes of intramedullary injections. Animal morbidity and the biomechanics of the joints were also improved as a result of the simplified procedure. Furthermore, our study suggested that an intramedullary volume in excess of 10 microL can lead to major vascular filling and so should be avoided.

  View details for DOI 10.1002/jbm.b.30872

  View details for Web of Science ID 000251802900034

• Seppo Santavirta: The life and work of an orthopaedic surgeon and scientist. A tribute from his friends JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Konttinen, Y. T., Goodman, S. B., Wright, T. 2008; 16: XII-XV

  View details for Web of Science ID 000257474600002

  View details for PubMedID 18612025

• Mouse femoral intramedullary injection model: technique and microCT scan validation. Journal of biomedical materials research. Part B, Applied biomaterials Zilber, S., Epstein, N. J., Lee, S., Larsen, M., Ma, T., Smith, R. L., Biswal, S., Goodman, S. B. 2008; 84 (1): 286-290

  Abstract

  The murine femoral intramedullary injection model is frequently used to examine the in vivo effects of biomaterials or cancer cells. The surgical technique includes a knee arthrotomy with patellar dislocation for intramedullary access. This study examined a less invasive surgical approach of direct injection of particles via the transpatellar tendon without patellar dislocation. By using polymethylmethacrylate injection and microCT scan, we found that, compared with the traditional technique, this new approach was more reproducible, less time consuming, and achieved identical volumes of intramedullary injections. Animal morbidity and the biomechanics of the joints were also improved as a result of the simplified procedure. Furthermore, our study suggested that an intramedullary volume in excess of 10 microL can lead to major vascular filling and so should be avoided.

  View details for PubMedID 17563101

• Biology summary JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Goodman, S. B., Goldberg, V., O'Keefe, R. 2008; 16: S76-S78

  View details for Web of Science ID 000257474600016

• Biodegradable micro-osmotic pump for long-term and controlled release of basic fibroblast growth factor JOURNAL OF CONTROLLED RELEASE Ryu, W., Huang, Z., Prinz, F. B., Goodman, S. B., Fasching, R. 2007; 124 (1-2): 98-105

  Abstract

  Microelectromechanical system (MEMS) technology not only provides the possibility of integration of multiple functions but also enables more precise control of dosing of therapeutic agents when the therapeutic window is very limited. Local delivery of basic fibroblast growth factor (bFGF) over a specific dose and time course is critical for mesenchymal tissue regeneration. However, bFGF is degraded quickly in vivo and difficulty of controlling the dose level impedes its effective use in angiogenesis and tissue regeneration. We constructed biodegradable micro-osmotic pumps based on MEMS technology for long-term controlled release of bFGF. The devices were constructed by micro-molding and thermal assembly of 85/15 poly(L-lactide-co-glycolide) sheets. The release of bFGF was regulated at 40 ng/day for four weeks; bioactivity was assessed by monitoring the growth of 3T3 fibroblasts. The proposed devices can be further miniaturized and used for the delivery of multiple therapeutic agents at the individual releasing schedules.

  View details for DOI 10.1016/j.jconrel.2007.08.024

  View details for PubMedID 17904240

• Wear particles, periprosthetic osteolysis and the immune system BIOMATERIALS Goodman, S. B. 2007; 28 (34): 5044-5048

  Abstract

  The immune system modulates many key biological processes in humans. However, the exact role of the immune system in particle-associated periprosthetic osteolysis is controversial. Human tissue retrieval studies, in vivo and in vitro experiments suggest that the immune response to polymer particles is non-specific and macrophage-mediated. Lymphocytes may modulate this response. However direct lymphocyte activation by polymer particle-protein complexes seems unlikely. However, metallic byproducts may complex with serum proteins and lead to a Type IV, lymphocyte-mediated immune reaction. In predisposed individuals, this reaction may rarely lead to persistent painful joint effusions, necessitating debridement and excision of the bearing surfaces of the prosthesis. In these patients, retrieved periprosthetic tissues exhibit histological evidence of perivascular lymphocytic cuffing. These findings are worrisome, given the fact that increasing numbers of metal-on-metal joint implants are being implanted in younger more active individuals worldwide.

  View details for DOI 10.1016/j.biomaterials.2007.06.035

  View details for PubMedID 17645943

• Coronal plane stability before and after total knee arthroplasty CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Siston, R. A., Goodman, S. B., Delp, S. L., Giori, N. J. 2007: 43-49

  Abstract

  The success of total knee arthroplasty depends in part on proper soft tissue management to achieve a stable joint. It is unknown to what degree total knee arthroplasty changes joint stability. We used a surgical navigation system to intraoperatively measure joint stability in 24 patients under going primary total knee arthroplasty to address two questions: (1) Is the total arc of varus-valgus motion after total knee arthroplasty different from the arc of varus-valgus motion in an osteoarthritic knee? (2) Does total knee arthroplasty produce equal amounts of varus/valgus motion (ie, is the knee "balanced")? We observed no difference between the total arc of varus-valgus motion before and after total knee arthroplasty; the total amount of motion was unchanged. On average, osteoarthritic knees were "unbalanced" but were "balanced" after prosthesis implantation. We found a negative correlation between the relative amount of varus/valgus motion in extension before and after prosthesis implantation in extension and a positive correlation between how well the knees were balanced after prosthesis implantation in extension and in flexion. Our data suggest immediately after implantation knees retain a greater than normal amount of varus-valgus motion, but this motion is more evenly distributed.

  View details for DOI 10.1097/BLO.0b013e318137a182

  View details for PubMedID 17621236

• The sequential expression profiles of growth factors from osteroprogenitors to osteoblasts In vitro TISSUE ENGINEERING Huang, Z., Nelson, E. R., Smith, R. L., Goodman, S. B. 2007; 13 (9): 2311-2320

  Abstract

  In this study, we delineate the sequential expression of selected growth factors associated with bone formation in vitro. Mineralization, osteocalcin, and alkaline phosphatase (ALP-2) were measured to monitor the differentiation and maturation of osteoprogenitor cells collected from C57BL mice. Bone-related growth factors, including transforming growth factor beta (TGF-beta), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), insulinlike growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP)-2, and BMP-7, were selected. Enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR) were used to measure growth factors at the protein and messenger ribonucleic acid (mRNA) level, respectively. The results found that ALP-2 expression increased progressively over time, whereas mineralization and osteocalcin did not become evident until culture day 14. VEGF and IGF-1 were upregulated early during proliferation. PDGF and TGF-beta mRNA expression was bimodal. FGF-2 and BMP-2 mRNAs were expressed only later in differentiation. FGF-2 mRNA signal levels were highest at day 14 and remained prominent through day 28 of culture. BMP-2 showed a similar profile as FGF-2. BMP-7 was not detectable using RT-PCR or ELISA. Strong correlations existed for the expression patterns between several early-response growth factors (VEGF, TGF-beta, and IGF-1) and were also evident for several late-response growth factors (BMP-2, PDGF, and FGF-2). Differential expression for grouped sets of growth factors occurs during the temporal acquisition of bone-specific markers as osteoprogenitor cell maturation proceeds in vitro.

  View details for DOI 10.1089/ten.2006.0423

  View details for PubMedID 17523879

• Modulation of allograft incorporation by growth factors over a prolonged continuous infusion of duration in vivo BONE Ma, T., Gutnick, J., Salazar, B., Larsen, M. D., Suenaga, E., Zilber, S., Huang, Z., Huddleston, J., Smith, R. L., Goodman, S. 2007; 41 (3): 386-392

  Abstract

  Morselized cancellous allograft bone is frequently used in the reconstruction of bone defects in cases of revision total joint replacement, trauma, spine fusion and treated infection. However, the initial lack of viable bone cells in morselized allograft bone significantly slows the process of graft incorporation compared to autograft bone. This study examined the effects of prolonged local infusion of the growth factors bone morphogenic protein-7 (BMP-7 or OP-1) and fibroblast growth factor-2 (FGF-2 or basic FGF) in the process of allograft incorporation using a rabbit tibial chamber model. New bone formation was evaluated by two indices, the activity of alkaline phosphatase and the level of birefringence. The markers of osteoclast-like cells were also measured. Without the infusion of the growth factors, lower levels of new bone formation were observed in the allograft group, compared to the autograft group. Infusion of growth factors FGF-2 and OP-1, singly or in combination, for 4 weeks, diminished this difference. The numbers of osteoclast-like cells were much higher in the allograft group before the growth factors were delivered. The infusion of FGF, singly, diminished this difference. However, the infusion of OP-1 or the combination of FGF and OP-1 did not decrease the number of osteoclast-like cells to a level comparable to autograft only. Local infusion of growth factors appears to be a useful adjunct to promote the incorporation of allograft bone in vivo.

  View details for DOI 10.1016/j.bone.2007.05.015

  View details for PubMedID 17613298

• Deltoid flap combined with fascia lata autograft for rotator cuff defects: a histologic study KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY McAdams, T. R., Knudsen, K. R., Yalamanchi, N., Chang, J., Goodman, S. B. 2007; 15 (9): 1144-1149

  Abstract

  The purpose of this study was to compare the histological characteristics of an autogenous fascia lata graft alone and a fascia lata graft combined with a deltoid flap in the reconstruction of rotator cuff tears. Ten New Zealand white rabbits were divided into two groups. Infraspinatus tendon defects (1 x 1 cm) were created in each animal. Reconstruction consisted of either a fascia lata graft alone or a fascia lata graft combined with a distally based deltoid flap. At 3 months, tissue harvest and histological analysis was performed. Compared to the fascia lata graft alone, there was significantly increased remodeling activity and neovascularization in the group that included a deltoid flap. Also, there was pronounced interdigitation at the graft/flap interface in the latter group. A mutually beneficial relationship may exist when an autogenous fascial graft is combined with a functional deltoid flap for reconstructing large rotator cuff defects.

  View details for DOI 10.1007/s00167-006-0281-9

  View details for PubMedID 17279424

• The effects of medications on bone JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Goodman, S. B., Jiranek, W., Petrow, E., Yasko, A. W. 2007; 15 (8): 450-460

  Abstract

  Medications taken for the treatment of arthritis and psychotropic and epileptic disorders, as well as anticoagulants, antacids, bisphosphonates, corticosteroids, and antineoplastic drugs, can profoundly affect bone metabolism. In some scenarios (eg, osteoporosis), these effects are intended; in others (eg, rickets, osteomalacia secondary to antiepileptic drugs), potentially adverse side effects of medications on bone may occur. Nonsteroidal anti-inflammatory drugs appear to delay fracture healing and bone ingrowth, although these effects are reversible. Disease-modifying antirheumatic drugs do not appear to affect bone metabolism adversely when taken in the low dosages currently prescribed. Bisphosphonates are useful in restoring bone mass in cases of postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, Paget's disease, and neoplastic conditions with bone loss and hypercalcemia. Corticosteroids and cancer chemotherapeutic agents generally affect bone adversely and increase fracture risk.

  View details for PubMedID 17664365

• Multimodal analgesia for orthopedic procedures ANESTHESIA AND ANALGESIA Goodman, S. B. 2007; 105 (1): 19-20

  View details for DOI 10.1213/01.ane.0000265444.73604.f0

  View details for Web of Science ID 000247444800007

  View details for PubMedID 17578947

• Utility of judet oblique x-rays in preoperative assessment of acetabular periprosthetic osteolysis: a preliminary study. American journal of orthopedics (Belle Mead, N.J.) Thomas, A., Epstein, N. J., Stevens, K., Goodman, S. B. 2007; 36 (7): E107-10

  Abstract

  Anteroposterior (AP) x-rays provide limited information about size and location of acetabular osteolytic lesions after total hip arthroplasty (THA). In the study reported here, we sought to determine the utility of oblique (Judet) x-rays in preoperative assessment of acetabular lesions. AP, anterior (obturator), and posterior (iliac oblique) x-rays of 10 patients (10 hips) who underwent revision THA were evaluated retrospectively. Mean osteolytic area was 790 mm2 (SD, 520 mm2) on anterior oblique x-rays and 384 mm2 (SD, 396 mm2) on AP x-rays (P = .005). Mean osteolytic area on posterior oblique x-rays was 512 mm2 (SD, 430 mm2) (P = .34). Judet x-rays were useful in determining size and location of acetabular osteolysis.

  View details for PubMedID 17694194

• Dissociation of the femoral head and trunion after constrained conversion total hip arthroplasty for poliomyelitis JOURNAL OF ARTHROPLASTY Spinnickie, A., Goodman, S. B. 2007; 22 (4): 634-637

  Abstract

  A conversion total hip arthroplasty using a 58-mm cementless shell and screws and constrained acetabular liner was performed in a 71-year-old patient with a nonunion of an intertrochanteric fracture and poliomyelitis with flail extremities. Preoperatively, the fractured lower extremity was painful and normally used by the patient for pivot transfers from his wheelchair. Five months postoperatively, the patient sustained complete dissociation of the trunion and femoral head, which was still located within the constrained liner. All other components were well fixated and properly positioned. The hip was revised successfully with a 40-mm femoral head and a nonconstrained liner with a 15 degrees elevated lip placed posterosuperiorly.

  View details for DOI 10.1016/j.arth.2006.05.011

  View details for PubMedID 17562428

• Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers. Journal of biomedical materials research. Part A Goodman, S. B., Ma, T., Spanogle, J., Chiu, R., Miyanishi, K., Oh, K., Plouhar, P., Wadsworth, S., Smith, R. L. 2007; 81 (2): 310-316

  Abstract

  The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.

  View details for PubMedID 17120215

• Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S. B., Ma, T., Spanogle, J., Chiu, R., Miyanishi, K., Oh, K., Plouhar, P., Wadsworth, S., Smith, R. L. 2007; 81A (2): 310-316

  Abstract

  The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.

  View details for DOI 10.1002/jbm.a.30983

  View details for Web of Science ID 000245688500006

• Kinetics of polymethylmethacrylate particle-induced inhibition of osteoprogenitor differentiation and proliferation JOURNAL OF ORTHOPAEDIC RESEARCH Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2007; 25 (4): 450-457

  Abstract

  Periprosthetic bone loss induced by implant wear debris may be a combined effect of osteolysis and reduced bone formation resulting from particle-induced suppression of osteoprogenitor differentiation. This study investigated the time-dependent effects of polymethylmethacrylate (PMMA) particles on the osteogenic capability of bone marrow osteoprogenitor cells during the early phase of differentiation. Murine bone marrow cells were challenged with PMMA particles (0.30% v/v) on the first day of growth in osteogenic medium. Particles were removed from culture after 1, 3, and 5 days, respectively, after which cell growth in osteogenic medium was continued until the 15th day. Bone marrow osteoprogenitor cells exposed to particles during the first 5 days of differentiation showed complete, irreversible inhibition of proliferation, alkaline phosphatase expression, and mineralization. Osteoprogenitors exposed to particles for more than 5 days showed the same degree of inhibition, while those exposed to particles for less than 5 days showed a diminished inhibitory response. Conditioned medium from particle-treated cells did not suppress osteogenic development, demonstrating that suppression of osteogenesis was not due to secreted inhibitory factors. This study has shown that the early phase of osteoprogenitor differentiation is a crucial time period during which exposure to PMMA particles causes irreversible inhibition of osteogenesis.

  View details for DOI 10.1002/jor.20328

  View details for PubMedID 17205559

• Surgical navigation for total knee arthroplasty: A perspective JOURNAL OF BIOMECHANICS Siston, R. A., Giori, N. J., Goodman, S. B., Delp, S. L. 2007; 40 (4): 728-735

  Abstract

  A new generation of surgical tools, known as surgical navigation systems, has been developed to help surgeons install implants more accurately and reproducibly. Navigation systems also record quantitative information such as joint range of motion, laxity, and kinematics intra-operatively. This article reviews the history of surgical navigation for total knee arthroplasty, the biomechanical principles associated with this technology, and the related clinical research studies. We describe how navigation has the potential to address three main challenges for total knee arthroplasty: ensuring excellent and consistent outcomes, treating younger and more physically active patients, and enabling less invasive surgery.

  View details for DOI 10.1016/j.jbiomech.2007.01.006

  View details for PubMedID 17317419

• Effects of local infusion of OP-1 on particle-induced and NSAID-induced inhibition of bone ingrowth in vivo. Journal of biomedical materials research. Part A Ma, T., Nelson, E. R., Mawatari, T., Oh, K. J., Larsen, D. M., Smith, R. L., Goodman, S. B. 2006; 79 (3): 740-746

  Abstract

  Excessive polyethylene wear particles from joint replacements may lead to periprosthetic osteolysis and loosening. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease fracture healing and bone ingrowth. We hypothesized that continuous local infusion of OP-1 (BMP-7) would increase local bone formation in the presence of two different adverse stimuli, polyethylene particles, and an oral NSAID. The Drug Test Chamber (DTC) was implanted in the proximal tibia of mature rabbits. The tissue growing into the chamber was exposed to OP-1 solution (110 ng/day), which was infused via an osmotic pump. Infusion of OP-1 alone for 6 weeks enhanced local bone formation in the chamber by 80% (p < 0.05) over infusion of carrier alone. In the presence of polyethylene particles, infusion of OP-1 increased local bone formation by 38% (p < 0.05) over treatment with particles and carrier. Oral administration of NSAID reduced local bone formation by 58% (p < 0.05); this suppressive effect caused by NSAIDS was completely reversed by the infusion of OP-1 (p < 0.05). These findings underline a potential role for local treatment with OP-1 to increase bone formation in the presence of potentially adverse stimuli such as polyethylene wear particles or NSAID use.

  View details for PubMedID 16988970

• Effects of local infusion of OP-1 on particle-induced and NSAID-induced inhibition of bone ingrowth in vivo JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Ma, T., Nelson, E. R., Mawatari, T., Oh, K. J., Larsen, D. M., Smith, R. L., Goodman, S. B. 2006; 79A (3): 740-746

  Abstract

  Excessive polyethylene wear particles from joint replacements may lead to periprosthetic osteolysis and loosening. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease fracture healing and bone ingrowth. We hypothesized that continuous local infusion of OP-1 (BMP-7) would increase local bone formation in the presence of two different adverse stimuli, polyethylene particles, and an oral NSAID. The Drug Test Chamber (DTC) was implanted in the proximal tibia of mature rabbits. The tissue growing into the chamber was exposed to OP-1 solution (110 ng/day), which was infused via an osmotic pump. Infusion of OP-1 alone for 6 weeks enhanced local bone formation in the chamber by 80% (p < 0.05) over infusion of carrier alone. In the presence of polyethylene particles, infusion of OP-1 increased local bone formation by 38% (p < 0.05) over treatment with particles and carrier. Oral administration of NSAID reduced local bone formation by 58% (p < 0.05); this suppressive effect caused by NSAIDS was completely reversed by the infusion of OP-1 (p < 0.05). These findings underline a potential role for local treatment with OP-1 to increase bone formation in the presence of potentially adverse stimuli such as polyethylene wear particles or NSAID use.

  View details for DOI 10.1002/jbm.a.30949

  View details for Web of Science ID 000242134700034

• Effects of orthopaedic wear particles on osteoprogenitor cells BIOMATERIALS Goodman, S. B., Ma, T., Chiu, R., Ramachandran, R., Smith, R. L. 2006; 27 (36): 6096-6101

  Abstract

  Wear particles from total joint arthroplasties are constantly being generated throughout the lifetime of an implant. Since mesenchymal stem cells and osteoprogenitors from the bone marrow are the precursors of osteoblasts, the reaction of these cells to orthopaedic wear particles is critical to both initial osseointegration of implants and ongoing regeneration of the periprosthetic bed. Particles less than 5 microm can undergo phagocytosis by mature osteoblasts, with potential adverse effects on cellular viability, proliferation and function. The specific effects are dependent on particle composition and dose. Metal and polymer particles in non-toxic doses stimulate pro-inflammatory factor release more than ceramic particles of a similar size. The released factors inhibit markers of bone formation and are capable of stimulating osteoclast-mediated bone resorption. Mesenchymal stem cells and osteoprogenitors are also profoundly affected by wear particles. Titanium and polymethylmethacrylate particles inhibit bone cell viability and proliferation, and downregulate markers of bone formation in a dose- and time-dependent manner. Future studies should delineate the molecular mechanisms by which particles adversely affect mesenchymal stems cells and the bone cell lineage and provide strategies to modulate these effects.

  View details for DOI 10.1016/j.biomaterials.2006.08.023

  View details for PubMedID 16949151

• The high variability of tibial rotational alignment in total knee arthroplasty Open Scientific Meeting of the Knee-Society Siston, R. A., Goodman, S. B., Patel, J. J., Delp, S. L., Giori, N. J. SPRINGER. 2006: 65–69

  Abstract

  Although various techniques are advocated to establish tibial rotational alignment during total knee arthroplasty, it is unknown which is most repeatable. We evaluated the precision and accuracy of five tibial rotational alignment techniques to determine whether computer-assisted navigation systems can reduce variability of tibial component rotational alignment when compared to traditional instrumentation. Eleven orthopaedic surgeons used four computer-assisted techniques that required identification of anatomical landmarks and one that used traditional extramedullary instrumentation to establish tibial rotational alignment axes on 10 cadaver legs. Two computer-assisted techniques (axes between the most medial and lateral border of the tibial plateau, and between the posterior cruciate ligament [PCL] and the anterior tibial crest) and the traditional technique were least variable, with standard deviations of 9.9 degrees, 10.8 degrees, and 12.1 degrees, respectively. Computer-assisted techniques referencing the tibial tubercle (axes between the PCL and the medial border or medial 1/3 of the tubercle) were most variable, with standard deviations of 27.4 degrees and 28.1 degrees. The axis between the medial border of the tibial tubercle and the PCL was internally rotated compared to the other techniques. None of the techniques consistently established tibial rotational alignment, and navigation systems that establish rotational alignment by identifying anatomic landmarks were not more reliable than traditional instrumentation.

  View details for DOI 10.1097/01.blo.0000229335.36900.a0

  View details for PubMedID 16906095

• Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis JOURNAL OF CLINICAL INVESTIGATION Paniagua, R. T., Sharpe, O., Ho, P. P., Chan, S. M., Chang, A., Higgins, J. P., Tomooka, B. H., Thomas, F. M., Song, J. J., Goodman, S. B., Lee, D. M., Genovese, M. C., Utz, P. J., Steinman, L., Robinson, W. H. 2006; 116 (10): 2633-2642

  Abstract

  Tyrosine kinases play a central role in the activation of signal transduction pathways and cellular responses that mediate the pathogenesis of rheumatoid arthritis. Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit-expressing gastrointestinal stromal tumors. We demonstrate that imatinib potently prevents and treats murine collagen-induced arthritis (CIA). We further show that micromolar concentrations of imatinib abrogate multiple signal transduction pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and TNF-alpha release, macrophage c-Fms activation and cytokine production, and fibroblast PDGFR signaling and proliferation. In our studies, imatinib attenuated PDGFR signaling in fibroblast-like synoviocytes (FLSs) and TNF-alpha production in synovial fluid mononuclear cells (SFMCs) derived from human RA patients. Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular responses may provide a powerful approach to treat RA and other inflammatory diseases.

  View details for DOI 10.1172/JCI28546

  View details for PubMedID 16981009

• Gene regulation ex vivo within a wrap-around tendon TISSUE ENGINEERING Li, K. W., Lindsey, D. P., Wagner, D. R., Giori, N. J., Schurman, D. J., Goodman, S. B., Smith, R. L., Carter, D. R., Beaupre, G. S. 2006; 12 (9): 2611-2618

  Abstract

  This study tested the hypothesis that physiologic tendon loading modulates the fibrous connective tissue phenotype in undifferentiated skeletal cells. Type I collagen sponges containing human bone marrow stromal cells (MSCs) were implanted into the midsubstance of excised sheep patellar tendons. An ex vivo loading system was designed to cyclically stretch each tendon from 0 to 5% at 1.0 Hz. The MSC-sponge constructs were implanted into 2 tendon sites: the first site subjected to tension only and a second site located at an artificially created wrap-around region in which an additional compressive stress was generated transverse to the longitudinal axis of the tendon. The induced contact pressure at the wraparound site was 0.55 +/- 0.12 MPa, as quantified by pressure-sensitive film. An MSC-sponge construct was maintained free swelling in the same bath as an unloaded control. After 2 h of tendon stretching, the MSC-sponge constructs were harvested and real-time PCR was used to quantify Fos, Sox9, Cbfa1 (Runx2), and scleraxis mRNA expression as markers of skeletal differentiation. Two hours of mechanical loading distinctly altered MSC differentiation in the wrap-around region and the tensile-only region, as evidenced by differences in Fos and Sox9 mRNA expression. Expression of Fos mRNA was 13 and 52 times higher in the tensile-only and wrap-around regions, respectively, compared to the free-swelling controls. Expression of Sox9 mRNA was significantly higher (2.5-3 times) in MSCs from the wraparound region compared to those from the tensile-only region or in free-swelling controls. In contrast, expression levels for Cbfa1 did not differ among constructs. Scleraxis mRNA was not detected in any construct. This study demonstrates that the physiologic mechanical environment in the wrap-around regions of tendons provides stimuli for upregulating early response genes and transcription factors associated with chondrogenic differentiation. These differentiation responses begin within as little as 2 h after the onset of mechanical stimulation and may be the basis for the formation of fibrocartilage that is typically found in the wrap-around region of mature tendons in vivo.

  View details for Web of Science ID 000240780900021

  View details for PubMedID 16995794

• Intraoperative passive kinematics of osteoarthritic knees before and after total knee arthroplasty JOURNAL OF ORTHOPAEDIC RESEARCH Siston, R. A., Giori, N. J., Goodman, S. B., Delp, S. L. 2006; 24 (8): 1607-1614

  Abstract

  Total knee arthroplasty is a successful procedure to treat pain and functional disability due to osteoarthritis. However, precisely how a total knee arthroplasty changes the kinematics of an osteoarthritic knee is unknown. We used a surgical navigation system to measure normal passive kinematics from 7 embalmed cadaver lower extremities and in vivo intraoperative passive kinematics on 17 patients undergoing primary total knee arthroplasty to address two questions: How do the kinematics of knees with advanced osteoarthritis differ from normal knees?; and, Does posterior substituting total knee arthroplasty restore kinematics towards normal? Osteoarthritic knees displayed a decreased screw-home motion and abnormal varus/valgus rotations between 10 degrees and 90 degrees of knee flexion when compared to normal knees. The anterior-posterior motion of the femur in osteoarthritic knees was not different than in normal knees. Following total knee arthroplasty, we found abnormal varus/valgus rotations in early flexion, a reduced screw-home motion when compared to the osteoarthritic knees, and an abnormal anterior translation of the femur during the first 60 degrees of flexion. Posterior substituting total knee arthroplasty does not appear to restore normal passive varus/valgus rotations or the screw motion and introduces an abnormal anterior translation of the femur during intraoperative evaluation.

  View details for DOI 10.1002/jor.20163

  View details for PubMedID 16770795

• Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta 3-induced chondrogenesis by adult human mesenchymal stem cells in vitro TISSUE ENGINEERING Miyanishi, K., Trindade, M. C., Lindsey, D. P., Beaupre, G. S., Carter, D. R., Goodman, S. B., Schurman, D. J., Smith, R. L. 2006; 12 (8): 2253-2262

  Abstract

  This study examined effects of varying magnitudes of intermittent hydrostatic pressure (IHP) applied for different times on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. hMSCs were exposed to 0.1, 1, and 10 MPa of IHP at a frequency of 1 Hz for 4 h/day for 3, 7, and 14 days in the presence of transforming growth factor (TGF-beta3). Chondrogenesis was characterized by gene expression, macromolecule production, and extracellular matrix deposition. Exposure of hMSCs to 0.1 MPa of IHP increased SOX9 and aggrecan mRNA expression by 2.2- and 5.6-fold, respectively, whereas type II collagen mRNA expression responded maximally at 10 MPa. Production of sulfated glycosaminoglycan responded to IHP of 1 MPa and 10 MPa, whereas collagen levels increased only at 10 MPa. Morphologically, matrix condensation occurred with increased IHP, concomitant with collagen expression. This study demonstrated that different levels of IHP differentially modulate hMSC chondrogenesis in the presence of TGF-beta3. The data suggest that tissue engineering of articular cartilage through application or recruitment of hMSCs can be facilitated by mechanical stimulation.

  View details for PubMedID 16968165

• Comparison of VEGF-producing cells in periprosthetic osteolysis BIOMATERIALS Spanogle, J. P., Miyanishi, K., Ma, T., Epstein, N. J., Smith, R. L., Goodman, S. B. 2006; 27 (21): 3882-3887

  Abstract

  The pro-angiogenic cytokine vascular endothelial growth factor (VEGF) has been implicated in periprosthetic osteolysis and subsequent aseptic loosening of implants following total hip arthroplasty (THA). The goal of this study was to investigate whether increased VEGF at the bone-implant interface is secondary to a greater number of VEGF-producing cells or to increased VEGF production by individual cells. Real time polymerase chain reaction (RT-PCR) techniques were used to assess the expression of VEGF mRNA (isoforms 121, 165, 189) in periprosthetic tissues from revision THAs. Immunofluorescence was used to determine both differences in overall cellularity and in VEGF-producing cell type (macrophages, fibroblasts, endothelial cells) between patients with periprosthetic osteolysis (OL) and a control group undergoing primary THA for osteoarthritis (OA). Quantitative analysis of VEGF release in periprosthetic membranes via RT-PCR demonstrated no significant difference in the per-cell mRNA production of VEGF isoforms 121 165, or 189 between OL and OA patient groups. Immunofluorescence showed both higher cellularity and higher overall VEGF expression in the OL group. Immunofluorescence also showed a significant increase in macrophages in the OL group, but no significant difference in the proportion of fibroblasts or endothelial cells between the OL and OA groups. Co-localization of CD68+ and CD11b+ macrophage fluorescent signals with VEGF signal was greater in the OL group than in the OA group. Our results demonstrate that increased VEGF in OL periprosthetic tissue compared to OA synovium is correlated to increased numbers of VEGF-producing CD68+ and CD11b+ macrophages. Impact statement: Aseptic loosening, caused in large part by OL, remains the major cause of failed THAs leading to revision surgery. At the bone-implant interface, we found increased numbers of macrophages-cellular mediators of OL-and increased VEGF expression. VEGF may be a possible target for therapeutic intervention in mitigating OL.

  View details for DOI 10.1016/j.biomaterials.2006.02.035

  View details for PubMedID 16540164

• Polymethylmethacrylate particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells. Journal of biomedical materials research. Part A Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2006; 77 (4): 850-856

  Abstract

  Aseptic implant loosening of total joint replacements often results from particle-mediated bone loss, which may be a combined effect of osteolysis and suppressed bone formation. Bone regeneration in the prosthetic bed depends on the activity of osteoblasts and their differentiation from osteoprogenitors in the bone marrow. This study investigated the effects of polymethylmethacrylate (PMMA) particles on the ability of bone marrow osteoprogenitors to differentiate into osteoblasts in vitro. Murine bone marrow cells challenged with PMMA particles on the first day of differentiation in osteogenic medium showed a dose-dependent decrease in osteoprogenitor proliferation, alkaline phosphatase expression, and mineralization. Undifferentiated bone marrow cells pretreated with PMMA particles in nonosteogenic medium for 5 days also showed a dose-dependent loss in osteogenic potential, which was sustained throughout subsequent growth in particle-free, osteogenic medium. Bone marrow cells challenged with PMMA particles after the fifth day of differentiation in osteogenic medium showed significant reductions in cellular proliferation, but not alkaline phosphatase expression and mineralization, indicating that bone marrow cells were most sensitive to particle treatment during the first 5 days of differentiation. This study demonstrated that PMMA particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells, which may contribute to periprosthetic bone loss and implant failure.

  View details for PubMedID 16596588

• Polymethylmethacrylate particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Chiu, R., Ma, T., Smith, R. L., Goodman, S. B. 2006; 77A (4): 850-856

  Abstract

  Aseptic implant loosening of total joint replacements often results from particle-mediated bone loss, which may be a combined effect of osteolysis and suppressed bone formation. Bone regeneration in the prosthetic bed depends on the activity of osteoblasts and their differentiation from osteoprogenitors in the bone marrow. This study investigated the effects of polymethylmethacrylate (PMMA) particles on the ability of bone marrow osteoprogenitors to differentiate into osteoblasts in vitro. Murine bone marrow cells challenged with PMMA particles on the first day of differentiation in osteogenic medium showed a dose-dependent decrease in osteoprogenitor proliferation, alkaline phosphatase expression, and mineralization. Undifferentiated bone marrow cells pretreated with PMMA particles in nonosteogenic medium for 5 days also showed a dose-dependent loss in osteogenic potential, which was sustained throughout subsequent growth in particle-free, osteogenic medium. Bone marrow cells challenged with PMMA particles after the fifth day of differentiation in osteogenic medium showed significant reductions in cellular proliferation, but not alkaline phosphatase expression and mineralization, indicating that bone marrow cells were most sensitive to particle treatment during the first 5 days of differentiation. This study demonstrated that PMMA particles inhibit osteoblastic differentiation of bone marrow osteoprogenitor cells, which may contribute to periprosthetic bone loss and implant failure.

  View details for DOI 10.1002/jbm.a.30697

  View details for Web of Science ID 000237792300022

• Total hip arthroplasty using the miniature anatomic medullary locking stem CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Oh, K., Imrie, S., Hwang, K., Ramachandran, R., Shegog, M., Goodman, S. B. 2006: 85-91

  Abstract

  We report the outcome of a prospective consecutive series of 52 primary total hip arthroplasties using the miniature porous-coated Anatomic Medullary Locking stem in patients with small anatomic proportions because of hip dysplasia or juvenile chronic arthritis. The mean age of the patients at the time of surgery was 28.7 years (range 14-56 years). The average body weight and height of the patients were 51.8 kg (range 38.5-78.3 kg) and 157.1 cm (range 142.2-183 cm), respectively. The stem was cementless in 40 hips and cemented in 12 hips because of poor bone stock. A cementless acetabular cup with screw was used in all hips. The average followup was 7.1 years (range, 3-15.6 years). The Harris hip scores improved from an average of 31.2 points (range, 3.1-68.8 points)preoperatively to 82.8 points (range, 61.1-96.6 points) at latest followup. Three of 12 (25%) cemented and two of 40 (5%) cementless stem were revised. Four of seven 42-44-mm cups were revised. The miniature Anatomic Medullary Locking cementless femoral stem provides a satisfactory outcome in patients with small anatomic proportions. However, wear and osteolysis with the use of a small cementless polyethylene liner remain challenges.

  View details for DOI 10.1097/01.blo.0000194670.77849.ea

  View details for Web of Science ID 000243020600017

  View details for PubMedID 16789062

• The effects of titanium and polymethylmethacrylate particles on osteoblast phenotypic stability JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Ramachandran, R., Goodman, S. B., Smith, R. L. 2006; 77A (3): 512-517

  Abstract

  Wear particles generated following total joint arthroplasty interact with cells at the periprosthetic margin and induce an inflammatory response that contributes to osteolysis, aseptic loosening, and implant failure. This study examined the long-term effects of particles from two commonly implanted materials, titanium (Ti) and polymethylmethacrylate (PMMA), on cell viability and metabolism over a 21-day time course, using the human osteoblast-like cell line MG-63. Addition of particles was not associated with increased cell death or nitric oxide production at the particle concentration chosen. Collagen production was increased with exposure to titanium particles, whereas alkaline phosphatase and osteocalcin expression remained unchanged following exposure to both types of particles. The data show that titanium but not PMMA particles shifts bone cell metabolism to preferentially produce fibrous tissue rather than bone.

  View details for DOI 10.1002/jbm.a.30649

  View details for Web of Science ID 000237431300009

• The effects of titanium and polymethylmethacrylate particles on osteoblast phenotypic stability. Journal of biomedical materials research. Part A Ramachandran, R., Goodman, S. B., Smith, R. L. 2006; 77 (3): 512-517

  Abstract

  Wear particles generated following total joint arthroplasty interact with cells at the periprosthetic margin and induce an inflammatory response that contributes to osteolysis, aseptic loosening, and implant failure. This study examined the long-term effects of particles from two commonly implanted materials, titanium (Ti) and polymethylmethacrylate (PMMA), on cell viability and metabolism over a 21-day time course, using the human osteoblast-like cell line MG-63. Addition of particles was not associated with increased cell death or nitric oxide production at the particle concentration chosen. Collagen production was increased with exposure to titanium particles, whereas alkaline phosphatase and osteocalcin expression remained unchanged following exposure to both types of particles. The data show that titanium but not PMMA particles shifts bone cell metabolism to preferentially produce fibrous tissue rather than bone.

  View details for PubMedID 16482550

• Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro TISSUE ENGINEERING Miyanishi, K., Trindade, M. C., Lindsey, D. P., Beaupre, G. S., Carter, D. R., Goodman, S. B., Schurman, D. J., Smith, R. L. 2006; 12 (6): 1419-1428

  Abstract

  This study examined the effects of intermittent hydrostatic pressure (IHP) and transforming growth factor-beta 3 on chondrogenesis of adult human mesenchymal stem cells (hMSCs) in vitro. Chondrogenic gene expression was determined by quantifying mRNA signal levels for SOX9, a transcription factor critical for cartilage development and the cartilage matrix proteins, aggrecan and type II collagen. Extracellular matrix production was determined by weight and histology. IHP was applied to hMSCs in pellet culture at a level of 10 MPa and a frequency of 1 Hz for 4 h per day for periods of 3, 7, and 14 days. hMSCs responded to addition of TGF-beta 3 (10 ng/mL) with a greater than 10-fold increase (p < 0.01) in mRNA levels for each, SOX9, type II collagen, and aggrecan during a 14-day culture period. Applying IHP in the presence of TGF-beta 3 further increased the mRNA levels for these proteins by 1.9-, 3.3-, and 1.6-fold, respectively, by day 14. Chondrogenic mRNA levels were increased with just exposure to IHP. Extracellular matrix deposition of type II collagen and aggrecan increased in the pellets as a function of treatment conditions and time of culture. This study demonstrated adjunctive effects of IHP on TGF-beta 3-induced chondrogenesis and suggests that mechanical loading can facilitate articular cartilage tissue engineering.

  View details for PubMedID 16846340

• Revision total hip arthroplasty in juvenile chronic arthritis - 17 revisions in 11 patients followed for 4-12 years ACTA ORTHOPAEDICA Goodman, S. B., Oh, K., Imrie, S., Hwang, K., Shegog, M. 2006; 77 (2): 242-250

  Abstract

  Revision total hip arthroplasty (THA) in patients with juvenile chronic arthritis (JCA) is complicated by the young age of the patient, poor bone stock and small physical proportions. We report the complications and outcome of a prospective series of 17 revision THAs in Charnley class C JCA patients.15 acetabular components and 10 femoral components were revised. 13 cementless cups, 2 reconstruction/roof rings and cemented cups, and 4 cemented and 6 cementless femoral stems were implanted. 2 proximal femoral allografts and 1 strut allograft were used. Age at revision was 32 (21-53) years. Follow-up averaged 7 (4-12) years.2 patients with cemented femoral stems developed loosening, osteolysis and fracture. Both were successfully revised to long-stem cementless implants with strut/proximal femoral allografts. 1 loose, worn cementless cup with osteolysis was revised. 1 patient with a peri-operative infection and late acetabular fracture had a loose, non-revised cementless cup. 1 case of sciatic nerve palsy occurred after revision using a reconstruction ring. 1 late infection necessitated resection arthroplasty. Harris hip scores improved from 53 (34-85) to 76 (47-96).Revision THA in JCA has a substantial complication rate, even in experienced hands. The problem of obtaining long-term stable fixation, osteolysis, and replenishment of lost bone stock are major difficulties.

  View details for DOI 10.1080/17453670610045975

  View details for PubMedID 16752285

• The variability of femoral rotational alignment in total knee arthroplasty. journal of bone and joint surgery. American volume Siston, R. A., Patel, J. J., Goodman, S. B., Delp, S. L., Giori, N. J. 2005; 87 (10): 2276-2280

  Abstract

  Several reference axes are used to establish femoral rotational alignment during total knee arthroplasty, but debate continues with regard to which axis is most accurately and easily identified during surgery. Computer-assisted navigation systems have been developed in an attempt to more accurately and consistently align implants during total knee arthroplasty, but it is unknown if navigation systems can improve the accuracy of femoral rotational alignment as compared with that achieved with more traditional techniques involving mechanical guides. The purposes of the present study were to characterize the variability associated with femoral rotational alignment techniques and to determine whether the use of a computer-assisted surgical navigation system reduced this variability.Eleven orthopaedic surgeons used five alignment techniques (including one computer-assisted technique and four traditional techniques) to establish femoral rotational alignment axes on ten cadaveric specimens, and the orientation of these axes was recorded with use of a navigation system. These derived axes were compared against a reference transepicondylar axis on each femur that was established after complete dissection of all soft tissues.There was no difference between the mean errors of all five techniques (p > 0.11). Only 17% of the knees were rotated <5 degrees from the reference transepicondylar axis, with alignment errors ranging from 13 degrees of internal rotation to 16 degrees of external rotation. There were significant differences among the surgeons with regard to their ability to accurately establish femoral rotational alignment axes (p < 0.001).All techniques resulted in highly variable rotational alignment, with no technique being superior. This variability was primarily due to the particular surgeon who was performing the alignment procedure. A navigation system that relies on directly digitizing the femoral epicondyles to establish an alignment axis did not provide a more reliable means of establishing femoral rotational alignment than traditional techniques did.

  View details for PubMedID 16203894

• The variability of femoral rotational alignment in total knee arthroplasty JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Siston, R. A., Patel, J. J., Goodman, S. B., Delp, S. L., Giori, N. J. 2005; 87A (10): 2276-2280

  Abstract

  Several reference axes are used to establish femoral rotational alignment during total knee arthroplasty, but debate continues with regard to which axis is most accurately and easily identified during surgery. Computer-assisted navigation systems have been developed in an attempt to more accurately and consistently align implants during total knee arthroplasty, but it is unknown if navigation systems can improve the accuracy of femoral rotational alignment as compared with that achieved with more traditional techniques involving mechanical guides. The purposes of the present study were to characterize the variability associated with femoral rotational alignment techniques and to determine whether the use of a computer-assisted surgical navigation system reduced this variability.Eleven orthopaedic surgeons used five alignment techniques (including one computer-assisted technique and four traditional techniques) to establish femoral rotational alignment axes on ten cadaveric specimens, and the orientation of these axes was recorded with use of a navigation system. These derived axes were compared against a reference transepicondylar axis on each femur that was established after complete dissection of all soft tissues.There was no difference between the mean errors of all five techniques (p > 0.11). Only 17% of the knees were rotated <5 degrees from the reference transepicondylar axis, with alignment errors ranging from 13 degrees of internal rotation to 16 degrees of external rotation. There were significant differences among the surgeons with regard to their ability to accurately establish femoral rotational alignment axes (p < 0.001).All techniques resulted in highly variable rotational alignment, with no technique being superior. This variability was primarily due to the particular surgeon who was performing the alignment procedure. A navigation system that relies on directly digitizing the femoral epicondyles to establish an alignment axis did not provide a more reliable means of establishing femoral rotational alignment than traditional techniques did.

  View details for DOI 10.2106/JBJS.D.02945

  View details for Web of Science ID 000232421500018

• Evaluation of methods that locate the center of the ankle for computer-assisted total knee arthroplasty CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Siston, R. A., Daub, A. C., Giori, N. J., Goodman, S. B., Delp, S. L. 2005: 129-135

  Abstract

  Accurate alignment of the mechanical axis of the limb is important to the success of a total knee arthroplasty. Although computer-assisted navigation systems can align implants more accurately than traditional mechanical guides, the ideal technique to determine the distal end point of the mechanical axis, the center of the ankle, is unknown. In this study, we evaluated the accuracy, precision, objectivity, and speed of five anatomic methods and two kinematic methods for estimating the ankle center in 11 healthy subjects. Magnetic resonance images were used to characterize the shape of the ankle and establish the true ankle center. The most accurate and precise anatomic method was establishing the midpoint of the most medial and most lateral aspects of the malleoli (4.5 +/- 4.1 mm lateral error; 2.7 +/- 4.5 mm posterior error). A biaxial model of the ankle (2.0 +/- 6.4 mm medial error; 0.3 +/- 7.6 mm anterior error) was the most accurate kinematic method. Establishing the midpoint of the most medial and most lateral aspects of the malleoli was an accurate, precise, objective, and fast method for establishing the center of the ankle.

  View details for DOI 10.1097/01.blo.0000170873.88306.56

  View details for PubMedID 16205151

• Rebuilding the skeleton - The intraoperative use of trabecular metal in revision total hip arthroplasty 4th Annual Spring Meeting on Current Concept in Joint Replacement Gross, A. E., Goodman, S. B. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2005: 91–93

  Abstract

  Cages provide a scaffold for restoration of bone stock in revision arthroplasty of the acetabulum. A major problem with cages is failure at 5 to 10 years due to loss of fixation. The present generation of cages are not made of a material that provides biologic fixation. Trabecular metal cups provide excellent biologic fixation and a favorable environment for bone graft remodeling. For large bone defects where there is not optimal contact with host bone at the correct anatomic level, a trabecular cup is placed against bone graft, fixed with screws, and protected by a cage into which the polyethylene cup is cemented. The initial stability is via the cage, but when graft remodeling takes place, the stress will be taken by the trabecular metal relieving the stress on the cage.

  View details for DOI 10.1016/j.arth.2005.03.020

  View details for Web of Science ID 000230134300025

  View details for PubMedID 15991140

• UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease ACTA ORTHOPAEDICA Epstein, N. J., Bragg, W. E., Ma, T., Spanogle, J., Smith, R. L., Goodman, S. B. 2005; 76 (3): 412-420

  Abstract

  We examined the effects of ultra-high molecular weight polyethylene (UHMWPE) particles on mononuclear cell proinflammatory gene expression in a novel murine model. We hypothesized that mononuclear cell gene transcription of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) would be upregulated by the addition of polyethylene particles in this murine intramedullary rod model.The model involved a stainless steel Kirschner wire inserted retrograde with a line-to-line fit in bilateral femora of C57bl/6 mice. Additionally, the right femora were injected with 3 x 10(9) UHMWPE particles. Mononuclear marrow cells were isolated by bone marrow aspiration and Ficoll-Paque centrifugation at 2, 4 and 10 weeks post-surgery. Total RNA was isolated and real-time RT-PCR was performed to quantify gene expression. Histological specimens of explanted femora were also analyzed to track the changes in periprosthetic tissue.UHMWPE particles stimulated gene transcription in mononuclear cells when examined at 2, 4 and 10 weeks post-surgery, compared to the rod-only group. Relative levels of IL-1beta and MCP-1 mRNA increased in a linear fashion over the 10-week time-course. IL-6 mRNA showed increased expression which peaked at 4 weeks. TNF-alpha mRNA expression was variable and reached a minimum at 4 weeks. The addition of UHMWPE particles stimulated ingress of macrophages and multinuclear cells of macrophage origin to the bone-implant interface.In this model, a single bolus of UHMWPE particles had a long-term effect on gene transcription in mononuclear cells which perpetuated a chronic inflammatory state. This murine model of intramedullary particle-induced inflammation simulates periprosthetic events associated with implant wear in humans, and may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.

  View details for DOI 10.1080/17453670510041321

  View details for PubMedID 16156472

• Interleukin-1 modulates periprosthetic tissue formation in an intramedullary model of particle-induced inflammation JOURNAL OF ORTHOPAEDIC RESEARCH Epstein, N. J., Warme, B. A., Spanogle, J., Ma, T., Bragg, B., Smith, R. L., Goodman, S. B. 2005; 23 (3): 501-510

  Abstract

  Interleukin-1 (IL-1) is a proinflammatory cytokine that has been implicated in wear-debris associated total joint replacement failure. We hypothesized that the absence of the IL-1 type-1 receptor would mitigate the inflammatory response to titanium particles and decrease periprosthetic inflammatory tissue in a murine intramedullary rod model.An intramedullary rod with and without commercially pure titanium particles was placed in the femora of 24 wild type mice (WT) and 24 mice lacking a functional type-1 receptor to IL-1. Femora were analyzed histologically and by ELISA of organ culture explant supernatants.The presence of titanium particles in WT mice stimulated increased expression of interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1) relative to rod only controls. In contrast, IL-6 and MCP-1 expression were diminished in IL-1r1-KO mice exposed to titanium particles. Additionally, the formation of a periprosthetic fibro-inflammatory membrane in IL-1r1-KO mice was blunted at 2 weeks when compared to that in wild-type mice. Inflammatory changes and the quality of periprosthetic bone of IL-1r1-KO mice was similar to WT mice in response to titanium particles.These results implicate IL-1 as an important modulator in the local inflammatory response to intramedullary titanium particles. MCP-1 appears to be significantly modulated in IL-1r1-KO mice in response to titanium particles. This may be responsible, in part, for the diminished periprosthetic membrane observed in IL-1r1-KO mice at 2 weeks. Expansion of this murine model of intramedullary particle-induced inflammation to other gene targets may contribute to a more mechanistic understanding of wear-debris associated prosthesis failure.

  View details for DOI 10.1016/j.orthres.2004.10.004

  View details for PubMedID 15885468

• Cemented total knee arthroplasty in patients with juvenile rheumatoid arthritis CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Thomas, A., Rojer, D., Imrie, S., Goodman, S. B. 2005: 140-146

  Abstract

  The optimal techniques and implants for total knee arthroplasty in patients with juvenile rheumatoid arthritis are controversial. We report the functional outcomes and complications of a series of 17 cemented total knee arthroplasties done by one surgeon during a 10-year period in which off-the-shelf implants were used, the posterior cruciate ligament was excised, and a lateral retinacular release was done. Preoperatively, all knees had severe loss of normal joint space and osteopenia on 3-foot, standing AP radiographs, lateral radiographs, and patellofemoral views. The patients were evaluated after a mean followup of 74 months (range, 36-116 months). The Knee Society scores improved from a mean of 38.9 +/- 23.9 points (range, 10-81 points) preoperatively to 81.9 +/- 16.6 points (range, 39-99 points) postoperatively. Range of motion showed significant improvement in all patients at the most recent followup. Ambulation scores improved significantly; nine of 10 patients (15 knees) were ambulatory after surgery. Complications included two transient regional pain syndromes and one patellofemoral subluxation requiring realignment. Cemented total knee arthroplasty with off-the-shelf implants, excision of the posterior cruciate ligament, and lateral retinacular release in patients with juvenile rheumatoid arthritis can provide substantial improvement in pain, deformity, ambulation, and function.Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

  View details for DOI 10.1097/01.blo.0000151440.81939.c5

  View details for PubMedID 15805949

• Temporal effects of a COX-2-selective NSAID on bone ingrowth. Journal of biomedical materials research. Part A Goodman, S. B., Ma, T., Mitsunaga, L., Miyanishi, K., Genovese, M. C., Smith, R. L. 2005; 72 (3): 279-287

  Abstract

  The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.

  View details for PubMedID 15666361

• Temporal effects of a COX-2-selective NSAID on bone ingrowth JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S. B., Ma, T., Mitsunaga, L., Miyanishi, K., Genovese, M. C., Smith, R. L. 2005; 72A (3): 279-287

  Abstract

  The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.

  View details for DOI 10.1002/jbm.a.30231

  View details for Web of Science ID 000227223200005

• Wear particulate and osteolysis 40th Anniversary Symposium on Acrylic Bone Cement Goodman, S. W B SAUNDERS CO-ELSEVIER INC. 2005: 41-?

  Abstract

  Total joint replacements of the hip and knee are generally highly successful, with satisfactory longevity and clinical results. Using modern biocompatible materials, optimal component design, and meticulous surgical technique, survivorship of cemented or cementless joint replacements is approximately 15 years with more than a 90% probability. The host's biologic response is critical to implant longevity. Particulate disease refers to the host's adverse biologic response to wear debris and byproducts generated from the prosthesis. Initially, emphasis was placed on particulate polymethylmethacrylate (cement disease), but more recently polyethylene wear debris has been underscored. Debris from several materials in sufficient quantities and physicochemical forms, however, can generate an inflammatory cascade resulting in periprosthetic bone destruction (osteolysis), jeopardizing long-term success of the implant.

  View details for DOI 10.1016/j.ocl.2004.06.015

  View details for PubMedID 15542121

• Pharmacologic modulation of periprosthetic osteolysis CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Trindade, M., Ma, T., Genovese, M., Smith, R. L. 2005: 39-45

  Abstract

  Wear and periprosthetic osteolysis of total joint replacements continue to be the most important problems in arthroplasty surgery. Despite the introduction of improved technologies including alternative bearing surfaces for TJRs, wear is inevitable because of relative movement at different interfaces and processes such as electrolysis and material degradation. Worn, clinically failing implants need to be followed closely and revised when appropriate. However, early wear and minor osteolysis do not result necessarily in progressive failure of the prosthesis. Indeed such cases may be followed up clinically and radiographically to establish the functional and biologic sequelae of wear and the timeline of these events. This scenario provides an opportunity to modulate the adverse biologic reaction associated with wear particles that includes chronic inflammation, the foreign body response, and periprosthetic bone destruction. Currently, immunological events associated with wear particles are becoming understood more clearly. Strategies to mitigate adverse processes associated with wear debris include local or systemic administration of immune modulators, signaling molecules, anti-inflammatory agents and growth factors, and altering osteoclast function. Ultimately, prevention of accelerated wear and periprosthetic osteolysis will be achieved with improved bearing surfaces and prosthetic designs.

  View details for DOI 10.1097/01/blo.0000149998.88218.05

  View details for PubMedID 15662302

• Total hip replacement: A successful interaction of biology, mechanics, and materials science CLINICAL ORTHOPAEDICS AND RELATED RESEARCH SANTAVIRTA, S., Goodman, S. B. 2005: 2-2

  View details for DOI 10.1097/01.blo.0000150100.14850.7a

  View details for Web of Science ID 000226145500001

  View details for PubMedID 15662298

• Total knee replacement in juvenile rheumatoid arthritis ORTHOPEDICS Rojer, D. E., Goodman, S. B. 2005; 28 (1): 39-45

  Abstract

  In general, longer operative times and in some cases increased blood requirements can be expected with TKA in patients with juvenile rheumatoid arthritis. Complications also are more frequent. Pain relief is usually good to excellent, and function and deformity are significantly improved. Range of motion after TKA for juvenile rheumatoid arthritis is usually less than that obtained in osteoarthritis, but still allows for dramatic improvements in performing activities of daily living (Figure 3).

  View details for PubMedID 15682575

• The current role of structural grafts and cages in revision arthroplasty of the hip Hip-Society 2004 Meeting Gross, A. E., Goodman, S. SPRINGER. 2004: 193–200

  Abstract

  Treating large segmental acetabular defects that comprise more than 50% of the acetabulum is one of the most difficult challenges in revision arthroplasty of the hip. One of the surgical options is a structural acetabular allograft. Unless these allografts are protected by a cage that extends from ilium to ischium, there is an unacceptable incidence of graft failure. The cage allows reconstruction at the correct anatomic level. It provides a scaffold for bone grafting (structural and morsellized). The use of cement to stabilize the cup allows the surgeon to adjust the cup position independent of the cage. The current generation of cages does not provide biologic fixation and with time may loosen or fracture. Recent experience with a combination of a trabecular metal shell protected by a cage may offer a more favorable environment for bone grafting with permanent biologic fixation of the cup cage construct.

  View details for DOI 10.1097/01.blo.0000149822.49890.5e

  View details for Web of Science ID 000225549900030

  View details for PubMedID 15577487

• Modified sliding trochanteric osteotomy in revision total hip arthroplasty JOURNAL OF ARTHROPLASTY Goodman, S., Pressman, A., Saastamoinen, H., Gross, A. 2004; 19 (8): 1039-1041

  Abstract

  Traditional trochanteric sliding osteotomy preserves the lateral aspect of the greater trochanter, the abductors, and vastus lateralis in continuity. Our modification uses a lateral approach to the hip and osteotomy immediately anterior to the insertion of the posterior capsule and external rotators onto the greater trochanter. The osteotomy and attached abductors and vastus lateralis are translated anteriorly, leaving the posterior capsule and external rotators attached to the proximal femur. This surgical approach preserves the posterior soft-tissue stabilizing structures that resist posterior dislocation of the hip. In a retrospective review of 2 consecutive 2-year series of acetabular component revisions only between 1997 and 2001, 4 of 27 acetabular revisions using a traditional trochanteric slide subsequently dislocated; only 1 of 30 subsequent cases using a modified sliding trochanteric osteotomy dislocated. Modified sliding trochanteric osteotomy facilitated surgical exposure and produced a trend toward a lower dislocation rate that did not reach statistical significance with the small numbers of patients available.

  View details for DOI 10.1016/j.arth.2004.03.023

  View details for PubMedID 15586340

• Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation. Journal of biomedical materials research. Part B, Applied biomaterials Warme, B. A., Epstein, N. J., Trindade, M. C., Miyanishi, K., Ma, T., Saket, R. R., Regula, D., Goodman, S. B., Smith, R. L. 2004; 71 (2): 360-366

  Abstract

  Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle-induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle-mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10-mm-long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin-6, monocyte chemotactic protein-1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle-induced intramedullary inflammation may facilitate cost-effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle-mediated periprosthetic osteolysis.

  View details for PubMedID 15389497

• Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Warme, B. A., Epstein, N. J., Trindade, M. C., Miyanishi, K., Ma, T., Saket, R. R., Regula, D., Goodman, S. B., Smith, R. L. 2004; 71B (2): 360-366

  Abstract

  Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle-induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle-mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10-mm-long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin-6, monocyte chemotactic protein-1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle-induced intramedullary inflammation may facilitate cost-effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle-mediated periprosthetic osteolysis.

  View details for DOI 10.1002/jbm.b.30120

  View details for Web of Science ID 000224846700018

• The role of cages and rings: When all else fails ORTHOPEDICS Gross, A. E., Goodman, S. 2004; 27 (9): 969-970

  View details for Web of Science ID 000223829900026

  View details for PubMedID 15487420

• Intermittent hydrostatic pressure inhibits matrix metalloproteinase and pro-inflammatory mediator release from human osteoarthritic chondrocytes in vitro OSTEOARTHRITIS AND CARTILAGE Trindade, M. C., Shida, J., Ikenoue, T., Lee, M. S., Lin, E. Y., Yaszay, B., Yerby, S., Goodman, S. B., Schurman, D. J., Smith, R. L. 2004; 12 (9): 729-735

  Abstract

  This study tested the hypothesis that intermittent hydrostatic pressure applied to human osteoarthritic chondrocytes modulates matrix metalloproteinase and pro-inflammatory mediator release in vitro.Human osteoarthritic articular chondrocytes were isolated and cultured as primary high-density monolayers. For testing, chondrocyte cultures were transferred to serum-free medium and maintained without loading or with exposure to intermittent hydrostatic pressure (IHP) at 10 MPa at a frequency of 1 Hz for periods of 6, 12 and 24 h. Levels of matrix metalloproteinase-2, -9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the pro-inflammatory mediators, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), released into the culture medium were assessed by ELISA. Matrix metalloproteinase activity was confirmed by zymographic analysis.In the absence of IHP, levels of MMP-2, TIMP-1, IL-6, and MCP-1 in the chondrocyte culture medium increased in a time-dependent manner. Application of IHP decreased MMP-2 levels at all time periods tested, relative to unloaded control cultures maintained for the same time periods. Although 84/82 kDa bands were faintly detectable by zymography, MMP-9 levels were not quantifiable in medium from loaded or unloaded cultures by ELISA. TIMP-1 levels were not altered in response to IHP at any time period tested. IL-6 and MCP-1 levels decreased in cultures exposed to IHP at 12 and 24 h, relative to unloaded control cultures maintained for the same time periods.IHP decreased release of MMP-2, IL-6 and MCP-1 by osteoarthritic chondrocytes in vitro suggesting that pressure influences cartilage stability by modulating chondrocyte expression of these degradative and pro-inflammatory proteins in vivo.

  View details for DOI 10.1016/j.joca.2004.05.008

  View details for PubMedID 15325639

• The role of implant alignment on stability and particles on periprosthetic osteolysis - A rabbit model of implant failure JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Fornasier, V. L., Goodman, S. B., Protzner, K., Kamel, M., Song, Y., Shojaci, A. 2004; 70B (2): 179-186

  Abstract

  The study objective was to determine the tissue response to polyethylene and/or titanium particles and the role that these play in peri-prosthetic osteolysis in a rabbit model of implant failure. Twenty-two mature rabbits were used. Unilateral tibial arthroplasty was performed on all of them. The test animals received implants that were intentionally rotationally unstable with reference to the host tibia in order to create a model of failure. The test rabbits were divided into three groups. Group 1 consisted of seven rabbits in which only the carrier was implanted. Group 2 consisted of seven rabbits that received only polyethylene particles suspended in the carrier. Group 3 consisted of eight rabbits that received a mixture of polyethylene and titanium alloy particles suspended in the carrier. The rabbits were sacrificed at 6 months post surgery. The entire knee, together with the immediately surrounding soft tissue, was retrieved. The position of the implant in each rabbit was assessed with reference to its alignment to the tibia. The number of inflammatory, foreign-body reactive cells, the presence of neovascularization, edema, and necrosis in the periprosthetic zones were recorded and assessed in a qualitative and semiquantitative manner. Quantitative histomorphometry was used to determine the proportion of implant surface that interfaced with osseous or fibrous tissue. Also assessed was the thickness and maturity of the fibrous tissue and the endosteal remodeling activity in the peri-implant bone counting both osteoclastic and osteoblastic activity. The results showed that implanted particles and misalignment of the implants combined to produce peri-prosthetic bone resorption. Bone resorption was found to be proportional to the degree of misalignment. The animals that received combined polyethylene/titanium particles had a greater degree of foreign-body and inflammatory response with osteolysis than the other groups. The combination of bio-material particles (polyethylene and titanium alloy) produced a greater degree of bone resorption than the single biomaterial particles (polyethylene). The amount of bone resorption surrounding the implant was directly proportional to the degree of misalignment of the implant.

  View details for DOI 10.1002/jbm.b.20038

  View details for Web of Science ID 000222949700002

• The role of implant alignment on stability and particles on periprosthetic osteolysis--A rabbit model of implant failure. Journal of biomedical materials research. Part B, Applied biomaterials Fornasier, V. L., Goodman, S. B., Protzner, K., Kamel, M., Song, Y., Shojaci, A. 2004; 70 (2): 179-186

  Abstract

  The study objective was to determine the tissue response to polyethylene and/or titanium particles and the role that these play in peri-prosthetic osteolysis in a rabbit model of implant failure. Twenty-two mature rabbits were used. Unilateral tibial arthroplasty was performed on all of them. The test animals received implants that were intentionally rotationally unstable with reference to the host tibia in order to create a model of failure. The test rabbits were divided into three groups. Group 1 consisted of seven rabbits in which only the carrier was implanted. Group 2 consisted of seven rabbits that received only polyethylene particles suspended in the carrier. Group 3 consisted of eight rabbits that received a mixture of polyethylene and titanium alloy particles suspended in the carrier. The rabbits were sacrificed at 6 months post surgery. The entire knee, together with the immediately surrounding soft tissue, was retrieved. The position of the implant in each rabbit was assessed with reference to its alignment to the tibia. The number of inflammatory, foreign-body reactive cells, the presence of neovascularization, edema, and necrosis in the periprosthetic zones were recorded and assessed in a qualitative and semiquantitative manner. Quantitative histomorphometry was used to determine the proportion of implant surface that interfaced with osseous or fibrous tissue. Also assessed was the thickness and maturity of the fibrous tissue and the endosteal remodeling activity in the peri-implant bone counting both osteoclastic and osteoblastic activity. The results showed that implanted particles and misalignment of the implants combined to produce peri-prosthetic bone resorption. Bone resorption was found to be proportional to the degree of misalignment. The animals that received combined polyethylene/titanium particles had a greater degree of foreign-body and inflammatory response with osteolysis than the other groups. The combination of bio-material particles (polyethylene and titanium alloy) produced a greater degree of bone resorption than the single biomaterial particles (polyethylene). The amount of bone resorption surrounding the implant was directly proportional to the degree of misalignment of the implant.

  View details for PubMedID 15264298

• A conical-collared intramedullary stem can improve stress transfer and limit micromotion CLINICAL BIOMECHANICS Mandell, J. A., Carter, D. R., Goodman, S. B., Schurman, D. J., Beaupre, G. S. 2004; 19 (7): 695-703

  Abstract

  The objective of this study was to quantify the effect of collar geometry on stress transfer and micromotion in idealized models of a cementless implant having an intramedullary stem.Intramedullary stems exist on several types of orthopaedic implants, including the femoral component of hip arthroplasties and segmental replacements used in the surgical treatment of a tumor or trauma in the diaphysis of a long bone.Using three-dimensional finite element analysis, we compared four idealized, straight-stemmed, axisymmetric prostheses: flat-collared (0 degrees), conical-collared (30 degrees and 60 degrees), and collarless tapered (80 degrees). We simulated axial and non-axial (20 degrees oblique) loads as well as non-ingrown and ingrown interface conditions.Without bone ingrowth, stress transfer to bone adjacent to the collar increased with collar angle. Micromotion at the distal stem increased moderately with collar angle from 0 degrees through 60 degrees, then increased markedly from 60 degrees to 80 degrees. With simulated bony ingrowth, the effect of the collar was greatly reduced.The results of this study suggest that the selection of collar angle represents a tradeoff between initial stress transfer and micromotion. Stems with conical collar angles in the range of 30-60 degrees can provide increased stress transfer compared to a flat collar design and reduced micromotion compared to a collarless tapered design.

  View details for DOI 10.1016/j.clinbiomech.2004.04.004

  View details for Web of Science ID 000223419500007

  View details for PubMedID 15288455

• Chronic coccidioidomycosis infection of the knee: a case report. American journal of orthopedics (Belle Mead, N.J.) Werle, J., Goodman, S. 2004; 33 (8): 409-411

  Abstract

  Coccidioidomycosis is a rare fungal infection caused by C immitis in endemic areas of the southwestern United States. Extrapulmonary hematogenous dissemination is a feared complication of the primary pulmonary disease. The musculoskeletal system can be involved, and disseminated musculoskeletal infections can be extremely difficult to eradicate. Surgical treatment of chronic bone and joint infections includes débridement and eventual arthrodesis for end-stage secondary osteoarthritis.

  View details for PubMedID 15379238

• Complications of ilioischial reconstruction rings in revision total hip arthroplasty JOURNAL OF ARTHROPLASTY Goodman, S., Saastamoinen, H., Shasha, N., Gross, A. 2004; 19 (4): 436-446

  Abstract

  The complications, management, and outcome of a consecutive series of 61 ilioischial reconstruction rings performed by 1 surgeon over a 15-year period are reported. Structural corticocancellous allografts were used in 48 cases. Twenty-seven cases had no complications, 9 had medical complications, and 5 had complications related to femoral revision. Other complications included 4 sciatic and 2 peroneal nerve palsies, 4 rings that lost fixation, 1 possibly loose ring, 3 fractured flanges, 3 loose cups, 7 dislocations, and 3 deep infections. Success, defined as a stable reconstruction with no further acetabular revision and bone graft incorporation, was 76%. We recommend a constrained acetabular liner to avoid dislocation in selected cases, slotting the ischial flange into bone for further ring stability and protection of the sciatic nerve.

  View details for DOI 10.1016/j.arth.2003.11.015

  View details for PubMedID 15188101

• Human interleukin-1-induced murine osteoclastogenesis is dependent on RANKL, but independent of TNF-alpha CYTOKINE Ma, T., Miyanishi, K., Suen, A., Epstein, N. J., Tomita, T., Smith, R. L., Goodman, S. B. 2004; 26 (3): 138-144

  Abstract

  Although interleukin-1 (IL-1) has been implicated in the pathogenesis of inflammatory osteolysis, the means by which it recruits osteoclasts and promotes bone destruction are largely unknown. Recently, a cytokine-driven, stromal cell-free mouse osteoclastogenesis model was established. A combination of macrophage colony stimulating factor (M-CSF) and receptor activator of NFkappaB ligand (RANKL) was proven to be sufficient in inducing differentiation of bone marrow hematopoietic precursor cells to bone-resorbing osteoclasts in the absence of stromal cells or osteoblasts. This study utilizes this model to examine the impact of human IL-1beta on in vitro osteoclastogenesis of bone marrow progenitor cells. We found that osteoclast precursor cells failed to undergo osteoclastogenesis when treated with IL-1 alone. In contrast, IL-1 dramatically up-regulated osteoclastogenesis by 2.5- to 4-folds in the presence of RANKL and M-CSF. The effect can be significantly blocked by IL-1 receptor antagonist (p < 0.01). Tumor necrosis factor-alpha (TNF-alpha) was undetectable in the culture medium of differentiating osteoclasts induced by IL-1. Adding exogenous TNF-alpha neutralizing antibody had no influence on the IL-1-induced effect as well. These results show that in the absence of stromal cells, IL-1 exacerbates osteoclastogenesis by cooperating with RANKL and M-CSF, while TNF-alpha is not involved in this IL-1-stimulated osteoclast differentiation pathway.

  View details for DOI 10.1016/j.cyto.2004.02.001

  View details for PubMedID 15135808

• Effects of interleukin-10 on titanium particle-induced macrophage transcription factor activation and cytokine expression in vitro. Journal of biomedical materials research. Part A Wong, N., Trindade, M. C., Patel, R., Yaszay, B., Goodman, S. B., Smith, R. L. 2004; 69 (1): 40-46

  Abstract

  This study tests the hypothesis that transcription factor activation by exposure of macrophages to titanium particles can be modulated by the addition of the antiinflammatory cytokine, interleukin 10 (IL-10). The experiments were carried out with primary human monocyte/macrophages that were treated in the presence or absence of IL-10 with and without exposure to titanium particles. The time course for experiments varied from 1 h-5 h for analysis of nuclear protein and up to 48 h for analysis of cytokine release. Transcription factor translocation to the nucleus was analyzed using electrophoretic gel shift assays and cytokine release was quantified by enzyme-linked immunosorbent assay. Addition of titanium particles increased release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta). In addition, titantium particle induced translocation of the transcription factors, NF-kappa B and NF-IL6, in the nucleus within 1 h. Treatment of macrophages with IL-10 prior to exposure to titanium particles decreased translocation of NF-IL6 but did not significantly alter nuclear levels of NF-kappa B. In addition, pretreatment of the cells with IL-10 decreased particle-induced cytokine release. These data show that antiinflammatory cytokines may provide a mechanism by which particle-induced inflammatory response may be modulated in vivo.

  View details for PubMedID 14999749

• Effects of interleukin-10 on titanium particle-induced macrophage transcription factor activation and cytokine expression in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Wong, N., Trindade, M. C., Patel, R., Yaszay, B., Goodman, S. B., Smith, R. L. 2004; 69A (1): 40-46

  Abstract

  This study tests the hypothesis that transcription factor activation by exposure of macrophages to titanium particles can be modulated by the addition of the antiinflammatory cytokine, interleukin 10 (IL-10). The experiments were carried out with primary human monocyte/macrophages that were treated in the presence or absence of IL-10 with and without exposure to titanium particles. The time course for experiments varied from 1 h-5 h for analysis of nuclear protein and up to 48 h for analysis of cytokine release. Transcription factor translocation to the nucleus was analyzed using electrophoretic gel shift assays and cytokine release was quantified by enzyme-linked immunosorbent assay. Addition of titanium particles increased release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta). In addition, titantium particle induced translocation of the transcription factors, NF-kappa B and NF-IL6, in the nucleus within 1 h. Treatment of macrophages with IL-10 prior to exposure to titanium particles decreased translocation of NF-IL6 but did not significantly alter nuclear levels of NF-kappa B. In addition, pretreatment of the cells with IL-10 decreased particle-induced cytokine release. These data show that antiinflammatory cytokines may provide a mechanism by which particle-induced inflammatory response may be modulated in vivo.

  View details for DOI 10.1002/jbm.a.20097

  View details for Web of Science ID 000220224600005

• Tenocyte response to cyclical strain and transforming growth factor beta is dependent upon age and site of origin BIORHEOLOGY Goodman, S. A., May, S. A., Heinegard, D., Smith, R. K. 2004; 41 (5): 613-628

  Abstract

  The effect of strain and transforming growth factor beta on equine tendon fibroblasts (tenocytes) was assessed in vitro. Tenocytes were isolated from flexor and extensor tendons of horses from foetal to 10 years of age. These cells were cultured until confluent on collagen-coated silicone dishes. Cyclic biaxial strain of 9+/-1% was applied at 0.5 Hz for 24 hours with or without added TGFbeta1 or 3 (10 ng/ml). Proliferation and synthetic responses were dependent on the tendon of origin. Neither strain nor TGFbeta caused flexor tenocytes to proliferate significantly, while strain alone did proliferate extensor tenocytes. TGFbeta, with or without strain, increased the incorporation of [3H]-proline and the production of types I and III collagen and COMP in both cell types, although the effect on COMP production was more marked in flexor tenocytes, perhaps reflecting the higher levels found in this tendon in vivo. Immature flexor tenocytes synthesised more collagen and COMP than those from mature animals, while age had little effect in extensor tenocytes. Our results suggest that tenocytes become differentiated at an early age and present tendon-specific responses.

  View details for Web of Science ID 000226305900002

  View details for PubMedID 15477668

• Interleukin 1 receptor antagonist inhibits localized bone formation in vivo JOURNAL OF RHEUMATOLOGY Ma, T., Miyanishi, K., Trindade, M. C., Genovese, M., Regula, D., Smith, R. L., Goodman, S. B. 2003; 30 (12): 2547-2552

  Abstract

  To test the in vivo effects of interleukin 1 receptor antagonist (IL-1ra) on bone formation and tissue ingrowth using an implantable bone ingrowth chamber that can be infused with test solutions.The bone ingrowth chamber was implanted in the proximal tibia of 10 mature NZW rabbits unilaterally. After an initial osseointegration period, the chambers were emptied of tissue and infused with either 0.05% bovine serum albumin (BSA) in phosphate buffered saline (PBS) or an IL-1ra solution for 4-week periods, which were separated by 4-week periods of no infusion. Tissue samples harvested from each chamber were snap-frozen and examined by histology and immunohistochemistry.The chambers were filled with longitudinally-oriented woven bone in a fibrovascular stroma during periods of infusion of 0.05% BSA in PBS or during periods without infusion. In contrast, infusion of IL-1ra for 4 weeks prevented tissue ingrowth in 4 of 6 chambers, and in 2 chambers exhibiting tissue ingrowth, bone formation was decreased. Bone formation remained at a lower level during the subsequent two 4-week periods without infusion after IL-1ra was discontinued, compared to samples prior to the IL-1ra treatment.The results showed that tissue ingrowth and bone formation were suppressed in an in vivo model by continuous infusion of IL-1ra at an early phase of tissue regeneration and differentiation.

  View details for PubMedID 14719192

• Efficacy of intraoperative blood collection and reinfusion in revision total hip arthroplasty. journal of bone and joint surgery. American volume Zarin, J., Grosvenor, D., Schurman, D., Goodman, S. 2003; 85-A (11): 2147-2151

  Abstract

  Patients undergoing revision total hip arthroplasty frequently require perioperative blood transfusion, increasing the risk for blood-borne disease and anaphylactic and hemolytic reactions. The purpose of this retrospective study was to evaluate the effect of intraoperative blood collection and reinfusion on net blood loss in patients undergoing revision hip arthroplasty.The medical records of 126 patients who had had a revision total hip arthroplasty with intraoperative blood salvage, with use of a collection and reinfusion device, during a twenty-eight-month period were reviewed. For comparison, the medical records of ninety-six patients who had undergone revision hip arthroplasty without intraoperative blood salvage were reviewed. Each of the 222 patients was categorized into a group on the basis of the type of revision.Patients who had a revision of the femoral and acetabular components (Group C) had significantly higher mean intraoperative and total blood loss than did those who had a revision of the femoral component only (Group A [p = 0.009 and p = 0.02, respectively]) or a revision of the acetabular component only (Group B [p = 0.0001 for both]). Total blood loss was not significantly different between Groups A and B. The mean amount of blood reinfused intraoperatively was 356 mL for the patients in Group A, 374 mL for the patients in Group B, and 519 mL for the patients in Group C. Regression analysis showed a significant decrease in net blood loss with intraoperative collection and reinfusion in Groups B (p = 0.002) and C (p = 0.0001) but not in Group A.Intraoperative collection and reinfusion substantially decreased net perioperative blood loss in patients who had a revision of both components (Group C) and in those who had a revision of the acetabular component (Group B). The use of intraoperative blood collection and reinfusion appears to be a valuable method of preserving blood volume in the perioperative period.

  View details for PubMedID 14630844

• Efficacy of intraoperative blood collection and reinfusion in revision total hip arthroplasty JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Zarin, J., Grosvenor, D., Schurman, D., Goodman, S. 2003; 85A (11): 2147-2151

  Abstract

  Patients undergoing revision total hip arthroplasty frequently require perioperative blood transfusion, increasing the risk for blood-borne disease and anaphylactic and hemolytic reactions. The purpose of this retrospective study was to evaluate the effect of intraoperative blood collection and reinfusion on net blood loss in patients undergoing revision hip arthroplasty.The medical records of 126 patients who had had a revision total hip arthroplasty with intraoperative blood salvage, with use of a collection and reinfusion device, during a twenty-eight-month period were reviewed. For comparison, the medical records of ninety-six patients who had undergone revision hip arthroplasty without intraoperative blood salvage were reviewed. Each of the 222 patients was categorized into a group on the basis of the type of revision.Patients who had a revision of the femoral and acetabular components (Group C) had significantly higher mean intraoperative and total blood loss than did those who had a revision of the femoral component only (Group A [p = 0.009 and p = 0.02, respectively]) or a revision of the acetabular component only (Group B [p = 0.0001 for both]). Total blood loss was not significantly different between Groups A and B. The mean amount of blood reinfused intraoperatively was 356 mL for the patients in Group A, 374 mL for the patients in Group B, and 519 mL for the patients in Group C. Regression analysis showed a significant decrease in net blood loss with intraoperative collection and reinfusion in Groups B (p = 0.002) and C (p = 0.0001) but not in Group A.Intraoperative collection and reinfusion substantially decreased net perioperative blood loss in patients who had a revision of both components (Group C) and in those who had a revision of the acetabular component (Group B). The use of intraoperative blood collection and reinfusion appears to be a valuable method of preserving blood volume in the perioperative period.

  View details for Web of Science ID 000186423600013

• COX-2 selective inhibitors and bone INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY Goodman, S. B., Ma, T., Genovese, M., Smith, R. L. 2003; 16 (3): 201-205

  Abstract

  Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed medications for relief of pain and inflammation. Recent animal studies using models of fracture healing and bone ingrowth suggest that NSAIDs (both non-selective NSAIDs and selective COX-2 inhibitors) adversely affect these bone-related processes. The dose and time-relationships of these medications and their resulting effects on bone have not yet been fully elucidated. Furthermore, whether COX-2 inhibitors and non-selective NSAIDs lead to clinically relevant adverse effects on bone healing in humans is unknown.

  View details for PubMedID 14611721

• Expression of nitric oxide, peroxynitrite, and apoptosis in loose total hip replacements JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Puskas, B. L., Menke, N. E., Huie, P., Song, Y., Ecklund, K., Trindade, M. C., Smith, R. L., Goodman, S. B. 2003; 66A (3): 541-549

  Abstract

  Nitric oxide (NO) is an effector molecule associated with inflammation, immune function, bone metabolism, and the induction of apoptosis. This study examined the role of NO, peroxynitrite (ONOO(-)), and apoptosis in cases of revision total hip replacements (THRs). We hypothesized that apoptosis and excess production of NO contribute to the inflammatory reaction to orthopedic biomaterial wear debris that is associated with loosening and osteolysis. Periprosthetic membranous specimens were collected from revised cemented acetabular components with simple loosening and ballooning osteolysis. Synovial samples from patients undergoing primary THR were used as controls. The presence of macrophages (CD68(+)) and levels of inducible nitric oxide synthase (INOS), endothelial nitric oxide synthase (EcNOS), ONOO(-) (Nitro, assayed by the amount of nitrated tyrosine residues), and apoptosis (TUNEL staining) were examined using immunohistochemistry. Increased expression for INOS, EcNOS, and ONOO(-) in both the loose/osteolytic and the loose/non-osteolytic groups was observed when compared to the synovium group. There were no significant differences between the loose/osteolytic group and loose/non-osteolytic group for these biologic markers. TUNEL staining showed a significant increase in apoptosis in the loose/osteolytic group compared to the loose/non-osteolytic group and synovial tissues. These findings suggest that NO and NO-derived molecules, such as ONOO(-), may be involved in sustaining the foreign-body reaction to wear debris. NO and ONOO(-) may prove to be useful markers of prosthetic loosening whereas apoptosis may be a marker distinguishing ballooning from simple osteolysis.

  View details for DOI 10.1002/jbm.a.10010

  View details for Web of Science ID 000185104800014

• Economics of one-stage versus two-stage bilateral total knee arthroplasties CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Macario, A., Schilling, P., Rubio, R., Goodman, S. 2003: 149-156

  Abstract

  Patients requiring bilateral total knee arthroplasties may have both joints replaced simultaneously during one hospitalization (one-stage) or during two separate hospitalizations (two-stage). The goals of the current study were to retrospectively analyze discharge patterns for 91 patients who had one-stage bilateral total knee arthroplasties and 32 patients who had two-stage surgeries, and to quantify their in-hospital costs and their costs if the patients were discharged from the hospital to an inpatient unit. Patients having one-stage and two-stage surgery were similar in age, gender, severity of illness (as measured by the American Society of Anesthesiologists Physical Status score), principal diagnosis, and ethnicity. Using a microcosting approach, the authors found that the average in-hospital costs for one-stage total knee arthroplasty (27,468 US dollars) were significantly lower (by 24%) than for two-stage total knee arthroplasty. However, 38% of patients who had the one-stage bilateral total knee arthroplasties were admitted to an acute rehabilitation unit, which had a mean cost of 6469 US dollars and length of stay of 9 days. In contrast, none of the patients who had the two-stage procedure required acute rehabilitation. Patients who had the two-stage procedure were discharged directly home (or with home health services) 42% of the time, versus 21% for patients who had the one-stage procedure. Patients from both groups were discharged to a skilled nursing facility approximately (1/2) of the time, accruing similar costs. Economic analyses of the one-stage procedure need to consider that these patients will require increased use of acute inpatient rehabilitation after hospital discharge.

  View details for DOI 10.1097/01.blo.0000079265.91782.ca

  View details for PubMedID 12966288

• Expression of nitric oxide, peroxynitrite, and apoptosis in loose total hip replacements. Journal of biomedical materials research. Part A Puskas, B. L., Menke, N. E., Huie, P., Song, Y., Ecklund, K., Trindade, M. C., Smith, R. L., Goodman, S. B. 2003; 66 (3): 541-549

  Abstract

  Nitric oxide (NO) is an effector molecule associated with inflammation, immune function, bone metabolism, and the induction of apoptosis. This study examined the role of NO, peroxynitrite (ONOO(-)), and apoptosis in cases of revision total hip replacements (THRs). We hypothesized that apoptosis and excess production of NO contribute to the inflammatory reaction to orthopedic biomaterial wear debris that is associated with loosening and osteolysis. Periprosthetic membranous specimens were collected from revised cemented acetabular components with simple loosening and ballooning osteolysis. Synovial samples from patients undergoing primary THR were used as controls. The presence of macrophages (CD68(+)) and levels of inducible nitric oxide synthase (INOS), endothelial nitric oxide synthase (EcNOS), ONOO(-) (Nitro, assayed by the amount of nitrated tyrosine residues), and apoptosis (TUNEL staining) were examined using immunohistochemistry. Increased expression for INOS, EcNOS, and ONOO(-) in both the loose/osteolytic and the loose/non-osteolytic groups was observed when compared to the synovium group. There were no significant differences between the loose/osteolytic group and loose/non-osteolytic group for these biologic markers. TUNEL staining showed a significant increase in apoptosis in the loose/osteolytic group compared to the loose/non-osteolytic group and synovial tissues. These findings suggest that NO and NO-derived molecules, such as ONOO(-), may be involved in sustaining the foreign-body reaction to wear debris. NO and ONOO(-) may prove to be useful markers of prosthetic loosening whereas apoptosis may be a marker distinguishing ballooning from simple osteolysis.

  View details for PubMedID 12918037

• Periprosthetic osteolysis: Induction of vascular endothelial growth factor from human monocyte/macrophages by orthopedic biomaterial particles 49th Annual Meeting of the Orthopaedic-Research-Society Miyanishi, K., Trindade, M. C., Ma, T., Goodman, S. B., Schurman, D. J., Smith, R. L. AMER SOC BONE & MINERAL RES. 2003: 1573–83

  Abstract

  VEGF and VEGF receptor, Flt-1, expression was observed in periprosthetic tissues surrounding loosened total joint implants. Exposure of monocyte/macrophages to titanium particles resulted in increased VEGF expression, p44/42 MAPK activation, and VEGF-dependent macrophage chemotaxis. Increased levels of angiogenic factors, such as VEGF, may be critically important in wear debris-induced implant loosening after total joint arthroplasty.Periprosthetic osteolysis after total hip arthroplasty occurs in association with formation of a vascularized granulomatous tissue in response to particulate debris.This study examined expression of vascular endothelial growth factor (VEGF) and the VEGF receptor in 10 periprosthetic tissues from loosened prostheses and quantified effects of titanium particles on VEGF release, intracellular signaling, and VEGF-dependent chemotaxis in primary cultures of human monocyte/macrophages.Double immunofluorescent staining showed that VEGF and Flt-1 co-localized with cells positive for the macrophage marker, CD11b, in the periprosthetic tissues. Monocyte/macrophages challenged with titanium particles showed a dose- and time-dependent release of VEGF ranging from 2.8- to 3.1-fold and exhibited increased expression of VEGF121 and VEGF165 mRNAs, reaching levels up to 5.0- and 8.6-fold, respectively, by 48 h (p < 0.01). Exposure of monocyte/macrophages to titanium particles upregulated phosphorylated-p44/42 mitogen-activated protein kinase (MAPK) within 30 minutes. Particle-induced activation of p44/42 MAPK and release of VEGF were dose-dependently suppressed by pretreatment of cells with PD98059, a specific inhibitor of p44/42 MAPK. Monocyte/macrophages challenged with titanium particles also showed a time-dependent activation of AP-1, a transcription factor associated with VEGF expression (p < 0.01). Supernatants from particle-challenged monocyte/macrophages increased macrophage chemotactic activity by 30%, which was significantly inhibited by anti-VEGF neutralizing antibody (p < 0.01).This study suggests that induction of VEGF release from monocyte/macrophages in response to orthopaedic biomaterial wear debris may contribute to periprosthetic osteolysis and implant loosening.

  View details for PubMedID 12968666

• Regulation of nitric oxide and bcl-2 expression by shear stress in human osteoarthritic Chondrocytes in vitro JOURNAL OF CELLULAR BIOCHEMISTRY Lee, M. S., Trindade, M. C., Ikenoue, T., Goodman, S. B., Schurman, D. J., Smith, R. L. 2003; 90 (1): 80-86

  Abstract

  Onset and progression of cartilage degeneration is associated with shear stress occurring in diarthrodial joints subjected to inappropriate loading. This study tested the hypothesis that shear stress induced nitric oxide is associated with altered expression of regulatory onco-proteins, bcl-2, and Fas (APO-1/CD95) and apoptosis in primary human osteoarthritic chondrocyte cultures. Shear stress induced membrane phosphatidylserine and nucleosomal degradation were taken as evidence of chondrocyte apoptosis. Application of shear stress upregulated nitric oxide in a dose-dependent manner and was associated with increases in membrane phosphatidylserine and nucleosomal degradation. Increasing levels of shear stress decreased expression of the anti-apoptotic factor, bcl-2, from 44 to 10 U/ml. Addition of the nitric oxide antagonists, L-N(5)-(1-iminoethyl) ornithine and Nomega-nitro-L-arginine methyl ester (L-NAME), reduced shear stress induced nucleosomal degradation by 62% and 74%, respectively. Inhibition of shear stress induced nitric oxide release by L-NAME coincided with a 2.7-fold increase of bcl-2, when compared to chondrocytes exposed to shear stress in the absence of L-NAME. These data suggest that shear stress induced nitric oxide is associated with changes in apoptotic regulatory factors that alter chondrocyte metabolism and may contribute to joint degeneration.

  View details for DOI 10.1002/jcb.10611

  View details for PubMedID 12938158

• What questions do patients undergoing lower extremity joint replacement surgery have? BMC HEALTH SERVICES RESEARCH Macario, A., Schilling, P., Rubio, R., Bhalla, A., Goodman, S. 2003; 3

  Abstract

  The value of the Internet to deliver preoperative education would increase if there was variability in questions patients want answered. This study's goal was to have patients consulting an orthopedic surgeon about undergoing either a total hip arthroplasty (THA) or a total knee arthroplasty (TKA) rate the importance of different questions concerning their care.We assembled questions patients might have about joint replacement surgery by analyzing the literature and querying a pilot group of patients and surgeons. Twenty-nine patients considering undergoing THA and 19 patients considering TKR completed a written survey asking them to rate 30 different questions, with a 5 point Likert scale from 1 (least important)--5 (most important).For patients considering THA or TKR, the 4 highest rated questions were: Will the surgery affect my abilities to care for myself?, Am I going to need physical therapy?, How mobile will I be after my surgery?, When will I be able to walk normally again? The mean percentage disagreement was 42% for questions answered by TKR patients and 47% for the THA group. Some patients gave a high rating to questions lowly rated by the rest of the group.Although there was enough agreement to define a core set of questions that should be addressed with most patients considering THA or TKA, some of the remaining questions were also highly important to some patients. The Web may offer a flexible medium for accommodating this large variety of information needs.

  View details for PubMedID 12823860

• Local infusion of FGF-2 enhances bone ingrowth in rabbit chambers in the presence of polyethylene particles. Journal of biomedical materials research. Part A Goodman, S. B., Song, Y., Yoo, J. Y., Fox, N., Trindade, M. C., Kajiyama, G., Ma, T., Regula, D., Brown, J., Smith, R. L. 2003; 65 (4): 454-461

  Abstract

  Osseointegration of porous-coated implants during revision arthroplasty procedures is often impeded due to the presence of residual granuloma, particulate debris, and a sclerotic, dysvascular bone bed. We hypothesized that local infusion of recombinant fibroblast growth factor (FGF-2) would increase bone ingrowth in an in vivo model of tissue differentiation in the rabbit tibia in the presence of phagocytosable polyethylene particles. A drug test chamber (DTC) was implanted in the proximal medial tibial metaphysis of mature rabbits unilaterally. The chamber contained a 1x 1 x 5-mm tunnel for tissue ingrowth, and was connected to an osmotic diffusion pump. FGF-2 was infused at dosages of 0, 0.5, 5, 50, or 500 ng/day for a 3-week period, with subsequent harvesting of the ingrown tissue after each 3-week treatment. The effects of ultrahigh molecular weight polyethylene particles (0.5-microm diameter) on tissue ingrowth were determined by adding particles to the chamber at concentrations of 5.8 x 10(11) (low dose) or 1.7 x 10(12) (high dose) particles/mL, with and without infusion of 50 ng/day of FGF for 3 weeks. The tissue forming in the chamber was harvested after each treatment for histologic processing and morphometric analysis of bone ingrowth. Statistical analysis was performed using parametric tests (ANOVA), nonparametric tests (Kruskal-Wallis test) and post hoc tests. In the absence of particles, infusion of 50 ng FGF-2 per day yielded the greatest amount of bone ingrowth. The high dose of particles suppressed bone ingrowth into the chamber, but the low dose particles did not (p = 0.0002, 95% confidence limits = 9.19-18.80). Infusion of 50 ng FGF-2 per day significantly increased net bone formation in the presence of high-dose UHMWPE particles (p = 0.039, 95% confidence limits = 1.41-6.79). There was a trend for decreased numbers of vitronectin-receptor positive (osteoclast-like) cells with the addition of FGF-2, compared to particles alone (p = 0.08). Local delivery of FGF-2 may prove useful in mitigating the adverse effects of wear debris (e.g., in treating early osteolytic lesions), and facilitating osseointegration of revision total joint replacements in situations where the bone bed is suboptimal and residual particles and granulomatous tissue are present.

  View details for PubMedID 12761835

• Local infusion of FGF-2 enhances bone ingrowth in rabbit chambers in the presence of polyethylene particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S. B., Song, Y., Yoo, J. Y., Fox, N., Trindade, M. C., KAJIYAMA, G., Ma, T., Regula, D., Brown, J., Smith, R. L. 2003; 65A (4): 454-461

  Abstract

  Osseointegration of porous-coated implants during revision arthroplasty procedures is often impeded due to the presence of residual granuloma, particulate debris, and a sclerotic, dysvascular bone bed. We hypothesized that local infusion of recombinant fibroblast growth factor (FGF-2) would increase bone ingrowth in an in vivo model of tissue differentiation in the rabbit tibia in the presence of phagocytosable polyethylene particles. A drug test chamber (DTC) was implanted in the proximal medial tibial metaphysis of mature rabbits unilaterally. The chamber contained a 1x 1 x 5-mm tunnel for tissue ingrowth, and was connected to an osmotic diffusion pump. FGF-2 was infused at dosages of 0, 0.5, 5, 50, or 500 ng/day for a 3-week period, with subsequent harvesting of the ingrown tissue after each 3-week treatment. The effects of ultrahigh molecular weight polyethylene particles (0.5-microm diameter) on tissue ingrowth were determined by adding particles to the chamber at concentrations of 5.8 x 10(11) (low dose) or 1.7 x 10(12) (high dose) particles/mL, with and without infusion of 50 ng/day of FGF for 3 weeks. The tissue forming in the chamber was harvested after each treatment for histologic processing and morphometric analysis of bone ingrowth. Statistical analysis was performed using parametric tests (ANOVA), nonparametric tests (Kruskal-Wallis test) and post hoc tests. In the absence of particles, infusion of 50 ng FGF-2 per day yielded the greatest amount of bone ingrowth. The high dose of particles suppressed bone ingrowth into the chamber, but the low dose particles did not (p = 0.0002, 95% confidence limits = 9.19-18.80). Infusion of 50 ng FGF-2 per day significantly increased net bone formation in the presence of high-dose UHMWPE particles (p = 0.039, 95% confidence limits = 1.41-6.79). There was a trend for decreased numbers of vitronectin-receptor positive (osteoclast-like) cells with the addition of FGF-2, compared to particles alone (p = 0.08). Local delivery of FGF-2 may prove useful in mitigating the adverse effects of wear debris (e.g., in treating early osteolytic lesions), and facilitating osseointegration of revision total joint replacements in situations where the bone bed is suboptimal and residual particles and granulomatous tissue are present.

  View details for DOI 10.1002/jbm.a.3000

  View details for Web of Science ID 000183285700007

• Delayed-onset Mycobacterium tuberculosis infection with staphylococcal superinfection after total knee replacement. American journal of orthopedics (Belle Mead, N.J.) Al-Shaikh, R., Goodman, S. B. 2003; 32 (6): 302-305

  Abstract

  Infection of a total joint replacement with Mycobacterium tuberculosis is uncommon in North America. This case describes a staphylococcal superinfection that masked an underlying tuberculous infection after total knee replacement and subsequent placement of a cement spacer. The patient had no evidence of M tuberculosis infection elsewhere. The most common explanation for these events is local reactivation of quiescent tuberculosis of the knee joint. The patient was treated successfully with surgical débridement, arthrodesis, and antituberculous medication.

  View details for PubMedID 12834194

• Human serum opsonization of orthopedic biomaterial particles: protein-binding and monocyte/macrophage activation in vitro. Journal of biomedical materials research. Part A Sun, D., Trindade, M. C., Nakashima, Y., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 2003; 65 (2): 290-298

  Abstract

  Wear particles generated after total joint arthroplasty activate monocyte/macrophages and incite formation of a granulomatous periprosthetic tissue associated with bone loss and implant loosening. This study tested the hypothesis that selective opsonization of orthopedic implant biomaterial wear particles by human serum proteins influences monocyte/macrophage activation. Serum protein binding to metallic, polymeric, and ceramic particles was determined by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual proteins bound to particles were subsequently identified using two-dimensional SDS-PAGE, microsequencing techniques, and SWISS-PROT analysis. Effects of selective protein opsonization on particle-induced monocyte/macrophage activation were assessed by quantification of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha release. Results from one-dimensional gel analyses revealed distinct serum protein-binding patterns specific for each material tested. Two-dimensional gel analysis together with amino acid sequencing of the prominent protein species confirmed the presence of albumin and alpha-1-antitrypsin bound to all particles tested. In contrast to the metallic particles, apolipoprotein was a major species associated with polymeric particles. Opsonization of PMMA particles with purified preparations of each of the identified proteins showed that albumin significantly enhanced particle-induced monocyte/macrophage activation. These data confirm orthopedic biomaterial specific binding of human serum proteins and demonstrate that albumin exacerbates particle-induced monocyte/macrophage activation. Alterations in the chemical and surface properties of orthopedic biomaterials to modulate protein interactions may improve implant longevity.

  View details for PubMedID 12734824

• Human serum opsonization of orthopedic biomaterial particles: Protein-binding and monocyte/macrophage activation in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Sun, D. H., Trindade, M. C., Nakashima, Y., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 2003; 65A (2): 290-298

  Abstract

  Wear particles generated after total joint arthroplasty activate monocyte/macrophages and incite formation of a granulomatous periprosthetic tissue associated with bone loss and implant loosening. This study tested the hypothesis that selective opsonization of orthopedic implant biomaterial wear particles by human serum proteins influences monocyte/macrophage activation. Serum protein binding to metallic, polymeric, and ceramic particles was determined by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Individual proteins bound to particles were subsequently identified using two-dimensional SDS-PAGE, microsequencing techniques, and SWISS-PROT analysis. Effects of selective protein opsonization on particle-induced monocyte/macrophage activation were assessed by quantification of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha release. Results from one-dimensional gel analyses revealed distinct serum protein-binding patterns specific for each material tested. Two-dimensional gel analysis together with amino acid sequencing of the prominent protein species confirmed the presence of albumin and alpha-1-antitrypsin bound to all particles tested. In contrast to the metallic particles, apolipoprotein was a major species associated with polymeric particles. Opsonization of PMMA particles with purified preparations of each of the identified proteins showed that albumin significantly enhanced particle-induced monocyte/macrophage activation. These data confirm orthopedic biomaterial specific binding of human serum proteins and demonstrate that albumin exacerbates particle-induced monocyte/macrophage activation. Alterations in the chemical and surface properties of orthopedic biomaterials to modulate protein interactions may improve implant longevity.

  View details for DOI 10.1002/jbm.a.10477

  View details for Web of Science ID 000182627600022

• Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles. Journal of biomedical materials research. Part A Goodman, S., Trindade, M., Ma, T., Lee, M., Wang, N., Ikenou, T., Matsuura, I., Miyanishi, K., Fox, N., Regula, D., Genovese, M., Klein, J., Bloch, D., Smith, R. L. 2003; 65 (1): 43-50

  Abstract

  Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

  View details for PubMedID 12635153

• Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Goodman, S., Trindade, M., Ma, T., Lee, M., Wang, N., Ikenou, T., Matsuura, I., Miyanishi, K., Fox, N., Regula, D., Genovese, M., Klein, J., Bloch, D., Smith, R. L. 2003; 65A (1): 43-50

  Abstract

  Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

  View details for DOI 10.1002/jbm.a.10279

  View details for Web of Science ID 000182453600007

• The role of the TH1 and TH2 immune responses in loosening and osteolysis of cemented total hip replacements JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A Arora, A., Song, Y., Chun, L., Huie, P., Trindade, M., Smith, R. L., Goodman, S. 2003; 64A (4): 693-697

  Abstract

  The mechanisms underlying the development of osteolysis and aseptic loosening have an impact on the longevity of total hip replacements (THRs). This study examines the specific roles of lymphocytes in the TH1 and TH2 subsets in osteolysis and aseptic loosening of THR. Tissue from periprosthetic regions from patients with loose, cemented acetabular components were used to determine the TH1 and TH2 cytokine profile. Twelve tissue specimens from patients with radiographic signs of osteolysis, and nine tissue specimens from patients with no signs of osteolysis were harvested during revision surgery. Immunohistochemistry using primary antibodies against CD3, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 was performed on frozen sections to determine the percentage of positive cells for each of the sections. No statistically significant differences in the percentage of positive cells expressing cytokines characteristic of the TH1 pathway (IFN-gamma, IL-2) or TH2 pathway (IL-4, IL-10) were found when comparing osteolytic and non-osteolytic tissues. However, significant numbers of T cells (averaging about 10% of the total cells) and TH1 and TH2 immune cytokines (averaging 3-5% of cells) implicate a possible role for immune processes at the prosthetic interface.

  View details for DOI 10.1002/jbm.a.10200

  View details for Web of Science ID 000182453500013

• The role of the TH1 and TH2 immune responses in loosening and osteolysis of cemented total hip replacements. Journal of biomedical materials research. Part A Arora, A., Song, Y., Chun, L., Huie, P., Trindade, M., Smith, R. L., Goodman, S. 2003; 64 (4): 693-697

  Abstract

  The mechanisms underlying the development of osteolysis and aseptic loosening have an impact on the longevity of total hip replacements (THRs). This study examines the specific roles of lymphocytes in the TH1 and TH2 subsets in osteolysis and aseptic loosening of THR. Tissue from periprosthetic regions from patients with loose, cemented acetabular components were used to determine the TH1 and TH2 cytokine profile. Twelve tissue specimens from patients with radiographic signs of osteolysis, and nine tissue specimens from patients with no signs of osteolysis were harvested during revision surgery. Immunohistochemistry using primary antibodies against CD3, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 was performed on frozen sections to determine the percentage of positive cells for each of the sections. No statistically significant differences in the percentage of positive cells expressing cytokines characteristic of the TH1 pathway (IFN-gamma, IL-2) or TH2 pathway (IL-4, IL-10) were found when comparing osteolytic and non-osteolytic tissues. However, significant numbers of T cells (averaging about 10% of the total cells) and TH1 and TH2 immune cytokines (averaging 3-5% of cells) implicate a possible role for immune processes at the prosthetic interface.

  View details for PubMedID 12601781

• Intermittent hydrostatic pressure inhibits shear stress-induced nitric oxide release in human osteoarthritic chondrocytes in vitro JOURNAL OF RHEUMATOLOGY Lee, M. S., Trindade, M. C., Ikenoue, T., Schurman, D. J., Goodman, S. B., Smith, R. L. 2003; 30 (2): 326-328

  Abstract

  To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro.Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software.Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression.Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.

  View details for PubMedID 12563690

• Meehanoregulation of human articular chondrocyte aggrecan and type II collagen expression by intermittent hydrostatic pressure in vitro JOURNAL OF ORTHOPAEDIC RESEARCH Ikenoue, T., Trindade, M. C., Lee, M. S., Lin, E. Y., Schurman, D. J., Goodman, S. B., Smith, R. L. 2003; 21 (1): 110-116

  Abstract

  This study addressed the hypothesis that duration and magnitude of applied intermittent hydrostatic pressure (IHP) are critical parameters in regulation of normal human articular chondrocyte aggrecan and type II collagen expression. Articular chondrocytes were isolated from knee cartilage and maintained as primary, high-density monolayer cultures. IHP was applied at magnitudes of 1, 5 and 10 MPa at 1 Hz for durations of either 4 h per day for one day (4 x 1) or 4 h per day for four days (4 x 4). Total cellular RNA was isolated and analyzed for aggrecan and type II collagen mRNA signal levels using specific primers and reverse transcription polymerase chain reaction (RT-PCR) nested with beta-actin primers as internal controls. With a 4x1 loading regimen, aggrecan mRNA signal levels increased 1.3- and 1.5-fold at 5 and 10 MPa, respectively, relative to beta-actin mRNA when compared to unloaded cultures. Changing the duration of loading to a 4x4 regimen increased aggrecan mRNA signal levels by 1.4-, 1.8- and 1.9-fold at loads of 1, 5 and 10 MPa, respectively. In contrast to the effects of IHP on aggrecan, type II collagen mRNA signal levels were only upregulated at loads of 5 and 10 MPa with the 4x4 loading regimen. Analysis of cell-associated protein by western blotting confirmed that IHP increased aggrecan and type II collagen in chondrocyte extracts. These data demonstrate that duration and magnitude of applied IHP differentially alter chondrocyte matrix protein expression. The results show that IHP provides an important stimulus for increasing cartilage matrix anabolism and may contribute to repair and regeneration of damaged or diseased cartilage.

  View details for Web of Science ID 000180869500015

  View details for PubMedID 12507587

• Protective effects of intermittent hydrostatic pressure on osteoarthritic chondrocytes activated by bacterial endotoxin in vitro JOURNAL OF ORTHOPAEDIC RESEARCH Lee, M. S., Ikenoue, T., Trindade, M. C., Wong, N., Goodman, S. B., Schurman, D. J., Smith, R. L. 2003; 21 (1): 117-122

  Abstract

  The role of continuous passive motion (CPM) in the management of septic arthritis and inflammatory arthritis remains of interest. CPM produces cyclic variations in intraarticular pressure that facilitates transport of fluid, nutrients, and solutes within and/or across the joint and stimulates chondrocyte metabolism. However, the precise mechanisms mediating the responses of chondrocytes to joint motion remain unclear. This study tested the hypothesis that dynamic mechanical loading counteracts effects of bacterial lipopolysaccharide (LPS), an inflammatory mediator, on chondrocyte metabolism. Intermittent hydrostatic pressure (IHP) (10 MPa for 4 h) was applied to human chondrocytes pretreated with LPS (1 microg/ml for 18 h). LPS activation of chondrocytes decreased mRNA signal levels of type II collagen by 67% and aggrecan by 56% and increased nitric oxide by 3.1-fold, monocyte chemotactic protein-1 mRNA signal levels by 6.5-fold, and matrix metalloproteinase-2 mRNA signal levels by 1.3-fold. Application of IHP to LPS-activated chondrocytes decreased nitric oxide synthase mRNA signal levels and nitric oxide levels in the culture medium. Exposure of LPS-activated chondrocytes to IHP upregulated type II collagen and aggrecan mRNA signal levels by 1.7-fold, relative to chondrocytes activated by LPS and maintained without loading. In addition, application of IHP decreased the upregulation in signal levels of monocyte chemotactic factor-1 and matrix metalloproteinase-2 following LPS activation by 45% and 15%, respectively. These data show that mechanical loading counteract effects of inflammatory agents, such as bacterial LPS, and suggest that postinfection sequelae are influenced by the presence or absence of joint loading.

  View details for Web of Science ID 000180869500016

  View details for PubMedID 12507588

• COX-2 selective NSAID decreases bone ingrowth in vivo JOURNAL OF ORTHOPAEDIC RESEARCH Goodman, S., Ma, T., Trindade, M., Ikenoue, T., Matsuura, I., Wong, N., Fox, N., Genovese, M., Regula, D., Smith, R. L. 2002; 20 (6): 1164-1169

  Abstract

  Whether non-steroidal anti-inflammatory drug (NSAID)-induced suppression of bone ingrowth is due to cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, or through a yet unidentified pathway is unknown. In this study, the effects of a non-specific COX-1 and COX-2 inhibitor, versus a specific COX-2 inhibitor on bone ingrowth and tissue differentiation are examined in vivo. Harvest chambers were implanted unilaterally in the tibiae of eight mature, New Zealand white rabbits. After a 6-week period for osseointegration of the chamber, the following oral treatments were given for 4 weeks each, followed by a harvest in each case: drinking water with no NSAID (control 1), Naproxen sodium--a COX-1 and COX-2 non-specific inhibitor at a dose of 110 mg/kg/day in the drinking water, drinking water with no NSAID (control 2), and Rofecoxib-a COX-2 inhibitor at a dose of 12.5 mg/day inserted directly into the rabbit's mouth. Harvested specimens were snap frozen, cut into serial 6 microm sections and stained with hematoxylin and eosin for general morphological characterization, and alkaline phosphatase (osteoblast marker). Sections were also processed for immunoperoxidase staining using monoclonal antibodies to identify cells expressing the vitronectin receptor (osteoclast-like cells). With drinking water alone, the percentage of bone ingrowth averaged 24.8 +/- 2.9% and 29.9 +/- 4.5% respectively. Naproxen sodium in the drinking water and oral Rofecoxib decreased bone ingrowth significantly (15.9 +/- 3.3%. p = 0.031 and 18.5 +/- 2+/-4%, p = 0.035 compared to drinking water respectively). Both Naproxen sodium (p = 0.026) and Rofecoxib (p = 0.02) decreased the number of CD51 positive osteoclast-like cells per section compared with drinking water alone. Rofecoxib decreased the area of osteoblasts per section area (p = 0.014) compared to controls, although the value for Naproxen sodium did not reach statistical significance. The results of the present study suggest that bone formation is suppressed by oral administration of an NSAID which contains a COX-2 inhibitor. COX-2 inhibitors currently taken for arthritis and other conditions may potentially delay fracture healing and bone ingrowth.

  View details for PubMedID 12472224

• Positive cytokine production in failed metal-on-metal total hip replacements ACTA ORTHOPAEDICA SCANDINAVICA Campbell, P. A., Wang, M., Amstutz, H. C., Goodman, S. B. 2002; 73 (5): 506-512

  Abstract

  Tissues surrounding failed conventional total hips have been shown to produce inflammatory cytokines that can induce osteoclastic bone resorption. We evaluated the cytokine profiles of tissues from 5 failed metal-on-metal total hip replacements. Serial frozen sections were stained using immunohistochemical and in situ hybridization techniques. Inflammatory and osteoclast-stimulating cytokines were noted in the tissues. As compared to a group of 5 metal-polyethylene hip tissues, we found fewer CD68 positive macrophages, and lower levels of TGF-beta and TNF-alpha, but no differences in CD3 positive lymphocytes, IL-1beta, IL-6 and PDGF-alpha in the metal-on-metal tissues. This may be due, in part to the presence of wear particles from sources other than the bearing surfaces. Thus, cytokines associated with bone resorption and implant loosening may occur in total hips despite the use of alternative bearing materials.

  View details for Web of Science ID 000178962000005

  View details for PubMedID 12440492

• Screw migration from total knee prostheses requiring subsequent surgery JOURNAL OF ARTHROPLASTY Shah, S. N., Schurman, D. J., Goodman, S. B. 2002; 17 (7): 951-954

  Abstract

  Complications in total knee arthroplasty directly related to hardware failure other than polyethylene wear are rare. We report 2 cases of symptomatic screw migration into the joint space from total knee prostheses. In the first case, a screw disengaged from a constrained condylar knee prosthesis. Arthroscopy using standard arthroscopy portals and a small arthrotomy were performed to remove the screw. In the second case, symptomatic screw disengagement and posterior migration from the tibial component of a posterior-stabilized prosthesis occurred. Revision with replacement of the polyethylene insert and locking screw was required.

  View details for DOI 10.1054/arth.2002.34827

  View details for PubMedID 12375258

• Factors influencing changes in articular cartilage following hemiarthroplasty in sheep JOURNAL OF ORTHOPAEDIC RESEARCH van der Meulen, M. C., Beaupre, G. S., Smith, R. L., Giddings, V. L., Allen, W. A., Athanasiou, K. A., Zhu, C. F., Mandell, J. A., Song, Y., Poser, R. D., Goodman, S. B. 2002; 20 (4): 669-675

  Abstract

  This study examined the relationship between acetabular cartilage properties after hemiarthroplasty surgery and surgical variables including femoral head size and position. Nineteen sheep received unilateral hip arthroplasties and were euthanized one year post-operatively to harvest the femora and acetabula. Cartilage histology, biochemistry and material properties were determined from samples located in the superior load-bearing region. Femoral head size mismatch, leg length difference, anterior-posterior and medial lateral offset and anteversion were measured. In the acetabulum. substantial cartilage degradation occurred with widespread librillation and significant changes in the biochemical and material properties compared to the intact contralateral joint. Regression analyses on the surgical variables explained 75-80% of the changes in tissue biochemistry but did not explain the material changes. Head size mismatch and leg length difference were the most significant contributors of the five variables examined and therefore may be critical to successful outcome in hemiarthroplasty.

  View details for Web of Science ID 000177191600005

  View details for PubMedID 12168653

• Effects of shear stress on nitric oxide and matrix protein gene expression in human osteoarthritic chondrocytes in vitro JOURNAL OF ORTHOPAEDIC RESEARCH Lee, M. S., Trindade, M. C., Ikenoue, T., Schurman, D. J., Goodman, S. B., Smith, R. L. 2002; 20 (3): 556-561

  Abstract

  Mechanical loading alters articular cartilage metabolism. However, mechanisms underlying intracellular signaling and communication between cells in response to mechanical stresses remain enigmatic. This study tested the hypothesis that shear stress-induced nitric oxide (NO) production participates in the regulation of matrix protein gene expression. The data presented here demonstrate that exposure of human osteoarthritic chondrocytes to a continuously applied shear stress (1.64 Pa) upregulated NO synthase gene expression and increased NO release by 1.8-, 2.4-, and 3.5-fold at 2, 6, and 24 h, respectively. Exposure of chondrocytes to a short duration of shear stress for 2 h resulted in the release of accumulation of NO in the culture medium. Exposure of chondrocytes to shear stress for 2, 6, and 24 h inhibited type II collagen mRNA signal levels by 27%, 18% and 20% after a constant post-shear incubation period of 24 h. Aggrecan mRNA signal levels were inhibited by 30%, 32% and 41% under identical conditions. Addition of an NO antagonist increased type II collagen mRNA signal levels by an average of 1.8-fold (137% of the un-sheared control) and reestablished the aggrecan mRNA signal levels by an average of 1.4-fold after shear stress (92% of the un-sheared control) (ANOVA p < 0.05). These data support the hypothesis that shear stress-induced NO release may influence the development of degenerative joint diseases by inhibiting matrix macromolecule synthesis.

  View details for Web of Science ID 000175621300022

  View details for PubMedID 12038631

• Mechanical evaluation of a carbonated apatite cement in the fixation of unstable intertrochanteric fractures ACTA ORTHOPAEDICA SCANDINAVICA Yetkinler, D. N., Goodman, S. B., Reindel, E. S., Carter, D., Poser, R. D., Constantz, B. R. 2002; 73 (2): 157-164

  Abstract

  We created three-part unstable intertrochanteric fractures in 6 pairs of aged, osteopenic, human, cadaveric femora. Fractures were reduced and fixed with a Dynamic Hip Screw (DHS) (Synthes, Paoli, PA). Two test groups were evaluated: 1. Fixation with DHS, and 2. Fixation with a DHS and calcium phosphate bone cement (Norian SRS (Skeletal Repair System)) augmentation of the fracture line and posteromedial calcar region of the proximal femur. Each femur was loaded to 1,650 N (2.5 body weight) for 10,000 cycles to simulate postoperative load transmission across the fracture construct during normal gait. The load was further increased successively by one body weight for another 10,000 cycles until failure. We evaluated fixation by measuring the amount of sliding of the lag screw of the DHS (shortening) and stiffness of the overall fracture construct (stability). SRS cement-augmented specimens had less shortening (1 mm versus 17 mm) and twice the initial construct stiffness compared to control specimens.

  View details for Web of Science ID 000175929300007

  View details for PubMedID 12079012

• Revision total knee arthroplasty using large distal femoral augments for severe metaphyseal bone deficiency: A preliminary study ORTHOPEDICS Werle, J. R., Goodman, S. B., Imrie, S. N. 2002; 25 (3): 325-327

  Abstract

  Managing severe structural femoral metaphyseal bone loss in revision total knee arthroplasty is a challenging problem facing the revision knee surgeon. This study assesses the use of large (30 mm) metal distal femoral augments to compensate for severe bone deficiencies. Hospital for Special Surgery scores, Knee Society scores, and range of motion improved after implantation of femoral components with 30-mm distal femoral augments. There was no radiographic evidence of loosening, and no implants had been revised at mean 37-month follow-up. This appears to be an acceptable technique based on the intermediate-term results.

  View details for PubMedID 11918039

• Polyethylene liner dissociation in Harris-Galante acetabular components - A report of 7 cases JOURNAL OF ARTHROPLASTY Werle, J., Goodman, S., Schurman, D., Lannin, J. 2002; 17 (1): 78-81

  Abstract

  Harris-Galante modular acetabular components (Zimmer, Warsaw, IN) have been used widely for primary and revision total hip arthroplasties. The survivorship of this implant has been well documented in the literature. Failure of the liner locking mechanism and subsequent dissociation of the polyethylene liner from the metal-backed shell is a potential cause of failure, however. We report 7 cases of liner dissociation and propose the mode of failure. The result in all cases was a well-fixed metal acetabular shell with a failed locking mechanism, which usually is managed by revision of the entire component. This procedure may be accompanied by the potential loss of acetabular bone stock, which should be replenished.

  View details for PubMedID 11805929

• Measurement of perioperative flexion-extension mechanics of the knee joint JOURNAL OF ARTHROPLASTY Giori, N. J., Giori, K. L., Woolson, S. T., Goodman, S. B., Lannin, J. V., Schurman, D. J. 2001; 16 (7): 877-881

  Abstract

  Perioperative knee mechanics currently are evaluated Perioperative knee mechanics currently are evaluated by measuring range of motion. This is an incomplete measurement, however, because the torque applied to achieve the motion is not measured. We hypothesized that a custom goniometer and force transducer could measure the torque required to passively flex a knee through its full range of motion. This measurement was done in the operating room immediately before and after surgery in 20 knees having total knee arthroplasty and 9 having surgery on another limb. Surgery changed the mechanics of 8 knees, whereas unoperated knees remained unchanged. This measurement technique is safe, easy, and repeatable. It improves on the current standard of perioperative knee measurement and can be applied to investigate the effects of surgery and rehabilitation on ultimate knee motion.

  View details for PubMedID 11607904

• Fibroblast expression of C-C chemokines in response to orthopaedic biomaterial particle challenge in vitro JOURNAL OF ORTHOPAEDIC RESEARCH Yaszay, B., Trindade, M. C., Lind, M., Goodman, S. B., Smith, R. L. 2001; 19 (5): 970-976

  Abstract

  C-C chemokines are soluble mediators that occur in a periprosthetic granuloma and influence recruitment, localization and activation of inflammatory cells. This study tested effects of titanium and polymethylmethacrylate (PMMA) particles on expression of selected C-C chemokines in cultured human fibroblasts. The C-C chemokines analyzed included monocyte chemoattractant protein-1. 2 (MCP-1. 2), monocyte inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation, normal T-cell expressed and secreted protein (RANTES). Interleukin-1 beta (IL-1 beta) served as a known stimulator of chemokine release while interleukin-6 (IL-6) expression served as a marker for fibroblast activation. Protein and mRNA signal levels were determined by ELISA and RT-PCR, respectively. The results demonstrated that exposure of fibroblasts to titanium and PMMA particles resulted in increased release of MCP-1 in a dose- and time-dependent manner. After 24 h, titanium particles maximally upregulated MCP-1 release 7-fold while PMMA particles increased MCP-1 levels 2-fold, when compared to unchallenged fibroblasts. MCP-2, MIP-1 alpha and RANTES levels remained unchanged following exposure of fibroblasts to titanium or PMMA particles at any concentration or time point tested. However, IL-1 beta stimulated release of MCP-1, MCP-2, and RANTES, but not MIP-1 alpha from the fibroblasts. IL-1 beta, not particles, exhibited the most prominent effect on MCP-1 mRNA levels. Increased release of MCP-1 from fibroblasts exposed to titanium and PMMA particles coincided with increased release of IL-6. This study suggests that release of chemoattractant factors from fibroblasts localized in periprosthetic membranes enhances the chronic inflammatory process leading to bone resorption and implant loosening.

  View details for PubMedID 11562149

• Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro BIOMATERIALS Trindade, M. C., Lind, M., Nakashima, Y., Sun, D. H., Goodman, S. B., Schurman, D. J., Smith, R. L. 2001; 22 (15): 2067-2073

  Abstract

  Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 microm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-alpha release by the cells following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-alpha release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.

  View details for PubMedID 11432585

• Chronic antigen-specific immune-system activation may potentially be involved in the loosening of cemented acetabular components JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Farber, A., Chin, R., Song, Y., Huie, P., Goodman, S. 2001; 55 (3): 433-441

  Abstract

  Previous studies have attempted to determine whether aseptic loosening and osteolysis are caused by a T cell-mediated type IV hypersensitivity reaction or a nonspecific foreign body reaction involving phagocytic macrophages. The purpose of this study was to examine the role of the B7-CD28 costimulatory pathway (which is indicative of an activated immune response) in loosening and osteolysis of total joint replacements (TJRs). We harvested periprosthetic tissues from 24 loose, cemented, all polyethylene, acetabular components in patients undergoing revision total hip replacement surgery for aseptic loosening. Prostheses were classified radiographically as to whether ballooning, scalloping osteolysis was present or not. Monoclonal antibodies were used to identify macrophages, antigen presenting cells (APCs) expressing B7-1 or B7-2, total T lymphocytes, and T cells expressing CD28 or CTLA-4. The large numbers of positive cells, including macrophages, T cells, and APCs in both groups are substantially higher than previously reported. Macrophages constituted the predominant cell type, the majority of which were APCs. B7-1 was expressed by 18.3% of all cells, and B7-2 was expressed by 61.0% of cells. Despite the fact that there were no statistically significant differences in expression of proteins in the B7-CD28 pathway between the osteolytic and nonosteolytic groups, the magnitude of positive staining suggests that the process of aseptic loosening (not osteolysis) may involve proteins of the B7-CD28 pathway, particularly B7-2. One possible antigenic stimulus is protein-coated particulate wear debris from prosthetic materials.

  View details for PubMedID 11255198

• Preoperative duplex ultrasonography evaluation for deep venous thrombosis in revision hip arthroplasty patients ORTHOPEDICS Wallace, B., Jeffrey, R. B., Goodman, S. B. 2001; 24 (6): 577-579

  Abstract

  In a prospective consecutive series, 53 revision hip arthroplasties were performed in 51 patients. Pre- and postoperative Duplex ultrasonography examinations were reviewed by an independent, experienced radiologist. Three of 51 patients (53 procedures) had evidence of chronic deep venous thrombosis (DVT) or other venous abnormality preoperatively, yielding an incidence of 5.6%. One (1.9%) patient developed an acute DVT postoperatively despite pharmacological and mechanical preventative measures. These results indicate the use of preoperative ultrasonography as a screening tool prior to revision hip arthroplasty is not warranted based on the low incidence of acute or chronic DVT detected preoperatively. Long-term anticoagulation, when necessary, can be based on the findings of a postoperative scan.

  View details for PubMedID 11430738

• Effect of osteogenic protein 1/collagen composite combined with impacted allograft around hydroxyapatite-coated titanium alloy implants is moderate JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Lind, M., Overgaard, S., Jensen, T. B., Song, Y., Goodman, S. B., Bunger, C., Soballe, K. 2001; 55 (1): 89-95

  Abstract

  This study evaluated the effects of osteogenic protein 1/collagen composite (OP-1/col) mixed with impacted allograft around hydroxyapatite (HA)-coated titanium alloy implants in a canine model. The aim of the study was to test different doses of OP-1 growth factor in a collagen composite for stimulatory effect on allograft incorporation around an implant. Unloaded implants were inserted in each proximal humerus of 16 skeletally mature dogs. The cylindrical implants (4 x 9 mm) coated with HA were initially surrounded by a 3-mm gap into which allograft mixed with OP-1/col was impacted. Two different doses of OP-1 were investigated. In eight animals 325 mg OP-1 protein and 130 mg bovine collagen type I as carrier were mixed with the allograft chips. This composite is identical to the clinically used OP-1 device called Novus. In another eight animals a lower dose of 65 mg OP-1 protein and 130 mg bovine collagen type I was used. Control implants placed in the contralateral humerus were surrounded by allograft mixed with collagen carrier only. The dogs were euthanized at 6 weeks. Implant fixation was determined by push-out testing. Bone ingrowth and bone formation were evaluated by quantitative histomorphometry on serial sections of the bone-implant interface. Impacted allograft together with low-dose OP-1 enhanced bone volume in a zone adjacent to HA-coated titanium alloy implants. The high dose had no effect on bone formation. Mechanical fixation, bone ingrowth, and bone volume in the gap near the original trabecular bone were unaffected by both low and high OP-1/col composite. In this model and observation period, the low dose of OP-1/col composite mixed with impacted allograft has a moderate effect on bone healing around HA-coated implants and no effect on implant fixation.

  View details for Web of Science ID 000166753400012

  View details for PubMedID 11426402

• Relationship between specific adverse life events and psychiatric disorders JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Tiet, Q. Q., Bird, H. R., Hoven, C. W., Moore, R., Wu, P., Wicks, J., Jensen, P. S., Goodman, S., Cohen, P. 2001; 29 (2): 153-164

  Abstract

  This study examines whether certain psychiatric disorders are associated more closely with adverse life events than other disorders are, and whether some adverse life events are associated with a specific group of disorders (e.g., depressive disorders), but not with other disorders (e.g., anxiety disorders). A probability sample of youth aged 9-17 at 4 sites is used (N = 1,285). Univariate and multivariate logistic regressions identify specific relationships between 25 adverse life events and 9 common child and adolescent psychiatric disorders, measured by the Diagnostic Interview Schedule for Children. Conduct Disorder, Oppositional Defiant Disorder, Major Depressive Disorder, and Dysthymia are significantly associated with many of the adverse life events examined, whereas Attention Deficit/Hyperactivity Disorder, Agoraphobia, and Social Phobia are related to very few. This study suggests that certain psychiatric disorders may be more closely associated with adverse life events than other psychiatric disorders are, and that some adverse life events seem to be related to specific types of disorders.

  View details for Web of Science ID 000167951200006

  View details for PubMedID 11321630

• In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery BIOMATERIALS Trindade, M. C., Lind, M., Sun, D., Schurman, D. J., Goodman, S. B., Smith, R. L. 2001; 22 (3): 253-259

  Abstract

  Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor-alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris.

  View details for PubMedID 11197500

• CCR7 expression and memory T cell diversity in humans JOURNAL OF IMMUNOLOGY Campbell, J. J., Murphy, K. E., Kunkel, E. J., Brightling, C. E., Soler, D., Shen, Z. M., Boisvert, J., Greenberg, H. B., Vierra, M. A., Goodman, S. B., Genovese, M. C., Wardlaw, A. J., BUTCHER, E. C., Wu, L. J. 2001; 166 (2): 877-884

  Abstract

  CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV). CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands. We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha(4)beta(7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7. CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7. The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.

  View details for Web of Science ID 000166259600023

  View details for PubMedID 11145663

• Sliding trochanteric osteotomy preserves favorable abductor biomechanics in revision total hip arthroplasty JOURNAL OF ARTHROPLASTY Romero, A. C., Imrie, S., Goodman, S. B. 2001; 16 (1): 55-64

  Abstract

  The outcome of sliding trochanteric osteotomy in revision total hip arthroplasty was assessed by comparing preoperative and postoperative static radiographic biomechanics and clinical hip abductor function of 22 consecutive operations (20 patients). Preoperative and postoperative pelvic radiographs were reviewed to quantify the biomechanical reconstruction of the hip abductor mechanism. Abductor muscle length and abductor moment arm were increased significantly (P <.05) by the operation. There was a significant (P <.05) increase in maximum degrees of active hip abduction from the preoperative to the postoperative state, an average of 32 months (range, 6-65 months) after surgery. The dysfunction index (a radiographic representation of hip torque) correlated positively (r =.63; P <.05) with active hip abduction. Sliding trochanteric osteotomy improves abductor biomechanics and may protect against trochanteric migration in revision total hip arthroplasty.

  View details for PubMedID 11172271

• Effects of local infusion of TGF beta on bone ingrowth in rabbit chambers JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Goodman, S., Song, Y., Chun, L., Aspenberg, P., Plouhar, P., Glancy, T., Regula, D., Smith, R. L. 2000; 53 (5): 475-479

  Abstract

  The local delivery of exogenous growth factors may help achieve a stable, long-lasting prosthetic interface around primary and revision joint replacements. This study examines the effects of local infusion of transforming growth factor beta (TGFbeta) in an in vivo model of tissue differentiation within bone. The Drug Test Chamber was implanted in the proximal medial tibial metaphysis of 8 mature rabbits unilaterally. The chamber contained a 1 x 1 x 5 mm canal for tissue ingrowth. The chamber was connected to an osmotic diffusion pump via polyvinyl tubing. 3.5 microg of recombinant TGFbeta1 was infused for 1 day or 1 week with subsequent harvesting of the ingrown tissue after 3 weeks. Each TGFbeta treatment was followed by two, 3-week infusions of carrier alone and harvesting of the ingrown tissue. TGFbeta for 1 day increased, and TGFbeta for 1 week decreased the percentage of bone in the chamber, compared to the initial control harvest after carrier alone. These changes, however, did not reach statistical significance. The number of vitronectin receptor positive cells in total, adjacent to bone and away from bone was higher after treatment with TGFbeta for 1 day, compared to 1 week. In an "unperturbed" bone ingrowth system (i.e., if bone ingrowth is not initially suppressed by other stimuli), this dose of TGFbeta did not enhance bone ingrowth using the DTC model.

  View details for PubMedID 10984694

• G-protein activity requirement for polymethylmethacrylate and titanium particle-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Trindade, M. C., Schurman, D. J., Maloney, W. J., Goodman, S. B., Smith, R. L. 2000; 51 (3): 360-368

  Abstract

  Periprosthetic granulomatous membranes consisting of fibroblasts, macrophages, lymphocytes, foreign body giant cells, and abundant particulate debris occur at sites of implant loosening. Previous studies demonstrate that fibroblasts respond to particulate debris through the release of interleukin-6 (IL-6), prostaglandin E(2), and matrix metalloproteinases in vitro. C-C chemokines are observed in granulomatous tissue surrounding loosened prosthetic implants and are released by macrophages and fibroblasts in response to particle challenge in vitro. This study tested the hypothesis that G protein activity is required for fibroblast activation by titanium and polymethylmethacrylate (PMMA) particles, and that inhibition of G protein activity would alter IL-6 and and monocyte chemoattractant protein-1 (MCP-1) release from activated fibroblasts. The specific inhibitor of G protein activity, pertussis toxin, was added to the fibroblasts to examine the effects of G protein activity with respect to the production of IL-6 and MCP-1 by orthopedic biomaterial-challenged fibroblasts in vitro. Interleukin-1beta (IL-1beta), a proven activator of MCP-1 and interleukin-6, was used as a positive control. Exposure of fibroblasts to titanium and polymethylmethacrylate (PMMA) particles resulted in a dose-dependent release of MCP-1 and IL-6. Challenge with PMMA particles at doses of 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 7-, 19-, and 22-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with PMMA particles at doses of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1-6 by 2.5-, 3.6-, 4. 3-, and 4.5-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Challenge with titanium particles at concentrations of 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 2.6-, 6.4-, 9.6-, and 10. 0-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone at 24 h. Challenge with titanium particles at concentrations of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of MCP-1 by 2.9-, 3.1-, 5.8-, 5.4-, and 5. 8-fold, respectively, compared to fibroblasts exposed to serum-free culture medium alone. Pretreatment of fibroblasts with pertussis toxin inhibited the release of interleukin-6 and MCP-1 from PMMA and titanium particle challenged fibroblasts in a dose-dependent manner. PMMA particle induced fibroblast IL-6 release was inhibited by 23.6% and 35.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle induced fibroblast IL-6 release was inhibited by 48.2% and 56.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. PMMA particle-induced fibroblast MCP-1 release was inhibited by 36.0%, 50.4%, and 60.1% with 2-, 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle-induced fibroblast MCP-1 release was inhibited by 15.5%, 53.2%, and 64.6% with 2-, 20-, and 200-ng/mL doses of pertussis toxin, respectively. This study suggests that fibroblasts localized in periprosthetic membranes are a source of macrophage chemoattractant factors and proinflammatory mediators that may influence granuloma formation and lead to periprosthetic bone resorption. Furthermore, this study shows that G proteins are involved in particle-induced fibroblast activation, as evidenced by decrease levels of particle induced IL-6 and MCP-1 release following pertussis toxin treatment. (c) 2000 John Wiley & Sons, Inc.

  View details for PubMedID 10880077

• Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity JOURNAL OF EXPERIMENTAL MEDICINE Kunkel, E. J., Campbell, J. J., Haraldsen, G., Pan, J. L., Boisvert, J., Roberts, A. I., Ebert, E. C., Vierra, M. A., Goodman, S. B., Genovese, M. C., Wardlaw, A. J., Greenberg, H. B., Parker, C. M., Butcher, E. C., Andrew, D. P., Agace, W. W. 2000; 192 (5): 761-767

  Abstract

  The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

  View details for PubMedID 10974041

• Induction of interleukin-6 release in human osteoblast-like cells exposed to titanium particles in vitro CALCIFIED TISSUE INTERNATIONAL Shida, J., Trindade, M. C., Goodman, S. B., Schurman, D. J., Smith, R. L. 2000; 67 (2): 151-155

  Abstract

  Orthopaedic wear debris induces release of bone-resorbing factors from macrophages and fibroblasts. However, the extent to which elemental metallic particles induce bone cells to express factors contributing to implant loosening remains unclear. This study showed that exposure of MG-63 osteoblast-like cells to titanium particles at a concentration of 0.30% v/v resulted in a 15-fold increase in IL-6 release into the culture medium after 24 hours, when compared with cells without particles. Northern blots revealed that exposure of MG-63 cells to titanium particles at a concentration of 0.30% v/v for 24 hours increased IL-6 mRNA signal levels by 9.6-fold, when compared with control cultures. Pretreatment of MG-63 cells with cytochalasin B prevented the particle-induced increase of IL-6 expression but did not alter the basal level of IL-6 release from cells cultured in the absence of particles. The protein kinase C inhibitor, H7, and the serine/threonine kinase inhibitor, genistein, abolished the particle-induced increase in IL-6 release at a concentration of 100 microM for each compound. In contrast, an inhibitor of protein kinase A, HA1004, had no effect on the particle-induced increase in IL-6 release. The transcription factors, nuclear factor IL-6 and nuclear factor kappa B, translocated into the nucleus within 1 hour of particle exposure. This study showed that osteoblast-like cells respond to titanium particles through increased expression of the proinflammatory cytokine, IL-6, in a process requiring phagocytosis and intracellular signaling pathways. These results suggest that osteoblasts play a direct role in implant loosening because of localized release of soluble mediators such as interleukin-6.

  View details for PubMedID 10920220

• Use of COX-2 specific inhibitors in operative and nonoperative management of patients with arthritis ORTHOPEDICS Goodman, S. B. 2000; 23 (7): S765-S768

  Abstract

  Arthritis is a major burden on society and the individual. Arthritis affects all age groups and races, and is more prevalent in women than men by approximately 1.65:1. Nearly one half of people aged > or = 65 years report the presence of arthritic symptoms; however, by no means is arthritis a disease of only the elderly. The burden of arthritis will continue to increase due to expected future increases in the size and age of the general population. Currently, the total costs of medical care and lost wages due to arthritis are in excess of 64 billion dollars per year in the United States. For the individual, arthritis may cause substantial pain, impair mobility, curtail physical activity, and have a negative impact on mental health. The two most common forms of arthritis, osteoarthritis and rheumatoid arthritis, have major health complications. From the perspective of the orthopedic surgeon, the aim of treatment of arthritic conditions includes early, accurate diagnosis and appropriate treatment to minimize pain and maximize function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as part of the medical management of patients with arthritis. These medications are effective in mitigating pain and inflammation associated with arthritis. However, side effects (most notably of the gastrointestinal tract) have limited the more widespread use of NSAIDs. The newer cyclooxygenase-2 (COX-2) inhibitors have proven to be efficacious and have demonstrated fewer gastrointestinal adverse effects. Furthermore, COX-2 inhibitors do not appear to adversely affect platelet function. For these reasons, consideration may be given to using COX-2 perioperatively, however, drug interactions must be closely monitored.

  View details for PubMedID 10914696

• Efficacy of postoperative blood salvage following total hip arthroplasty in patients with and without deposited autologous units JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Grosvenor, D., GOYAL, V., Goodman, S. 2000; 82A (7): 951-954

  Abstract

  Patients undergoing total hip replacement routinely receive perioperative blood transfusions, increasing their risk of blood-borne disease, isoimmunization, anaphylactic reaction, and hemolytic reaction. The purpose of this retrospective, case-control study was to evaluate the effect of postoperative blood salvage on the need for allogeneic transfusion following total hip replacement.We reviewed the medical records of ninety consecutive patients who, during a twelve-month period, had undergone unilateral, elective total hip replacement that included use of a postoperative blood salvage device. For comparison, we reviewed the medical records of ninety consecutive patients who had undergone total hip replacement without postoperative blood salvage. Overall, 156 patients had complete medical records and were included in the study.Eight (10 percent) of the patients who had been treated with a drain and seventeen (23 percent) of the patients who had been treated without a drain received allogeneic transfusions. Of the nineteen patients who had not deposited autologous blood, all six without postoperative blood salvage required allogeneic transfusion. With control for other variables in the model, regression analysis showed a significantly increased risk of allogeneic transfusion among patients who had undergone total hip replacement without postoperative blood salvage (p = 0.0028) and without having predonated autologous units (p = 0.0001).Despite a limited sample size, the study results showed that postoperative blood salvage significantly reduced the risk of allogeneic transfusion among patients managed with total hip replacement, whether or not they had deposited autologous blood (p < 0.0001). With control for donated units, age, gender, preoperative hematocrit, intraoperative blood loss, and cementless technique, patients who were treated without postoperative blood salvage were approximately ten times more likely to require allogeneic transfusion than were patients who had a drain.

  View details for Web of Science ID 000088080300006

• Monocyte migration inhibitory factor synthesis and gene expression in particle-activated macrophages CYTOKINE Lind, M., Trindade, M. C., Schurman, D. J., Goodman, S. B., Smith, R. L. 2000; 12 (7): 909-913

  Abstract

  This study analysed MIF mRNA and protein expression in human macrophages exposed in vitro to polymethylmethacryate and titanium alloy particles. MIF levels released from macrophages without exposure to particles were in the range of 2-4 ng/ml. Exposure of macrophages to particles as demonstrated increased MIF release at 0. 075%-0.225% v/v particle concentration, which was maximal at 12-24 h. MIF mRNA signal levels in cells with and without particles at a concentration of 0.075% showed no significant differences in a time course experiment. The profile of MIF release in response to increasing particle concentration coincided with increased release of lactate dehydrogenase. The viability of the cells was unchanged by the addition of particles as determined by 3H-thymidine uptake. These data suggest that MIF expression may represent an independent macrophage response to locally high particle concentrations.

  View details for Web of Science ID 000088220900009

  View details for PubMedID 10880235

• Efficacy of postoperative blood salvage following total hip arthroplasty in patients with and without deposited autologous units. journal of bone and joint surgery. American volume Grosvenor, D., GOYAL, V., Goodman, S. 2000; 82-A (7): 951-954

  Abstract

  Patients undergoing total hip replacement routinely receive perioperative blood transfusions, increasing their risk of blood-borne disease, isoimmunization, anaphylactic reaction, and hemolytic reaction. The purpose of this retrospective, case-control study was to evaluate the effect of postoperative blood salvage on the need for allogeneic transfusion following total hip replacement.We reviewed the medical records of ninety consecutive patients who, during a twelve-month period, had undergone unilateral, elective total hip replacement that included use of a postoperative blood salvage device. For comparison, we reviewed the medical records of ninety consecutive patients who had undergone total hip replacement without postoperative blood salvage. Overall, 156 patients had complete medical records and were included in the study.Eight (10 percent) of the patients who had been treated with a drain and seventeen (23 percent) of the patients who had been treated without a drain received allogeneic transfusions. Of the nineteen patients who had not deposited autologous blood, all six without postoperative blood salvage required allogeneic transfusion. With control for other variables in the model, regression analysis showed a significantly increased risk of allogeneic transfusion among patients who had undergone total hip replacement without postoperative blood salvage (p = 0.0028) and without having predonated autologous units (p = 0.0001).Despite a limited sample size, the study results showed that postoperative blood salvage significantly reduced the risk of allogeneic transfusion among patients managed with total hip replacement, whether or not they had deposited autologous blood (p < 0.0001). With control for donated units, age, gender, preoperative hematocrit, intraoperative blood loss, and cementless technique, patients who were treated without postoperative blood salvage were approximately ten times more likely to require allogeneic transfusion than were patients who had a drain.

  View details for PubMedID 10901309

• Osteogenic protein 1 device stimulates bone healing to hydroxyapaptite-coated and titanium implants JOURNAL OF ARTHROPLASTY Lind, M., Overgaard, S., Song, Y., Goodman, S. B., Bunger, C., Soballe, K. 2000; 15 (3): 339-346

  Abstract

  This study evaluated the effects of osteogenic protein 1 (OP-1) placed in a gap around uncoated and hydroxyapatite (HA)-coated implants. Unloaded cylindrical titanium alloy implants were inserted in the femoral condyles of 16 skeletally mature dogs surrounded by a 3-mm gap. The gap around the implants was filled with 325 microg OP-1 in 130 mg bovine collagen type I as carrier (OP-1 device) or collagen carrier alone or left empty. All groups were tested with both HA-coated and uncoated implants, and the animals were sacrificed after 6 weeks. Implant fixation was determined by push-out test. Bone ongrowth and bone formation were evaluated by quantitative histomorphometry. OP-1 device enhanced mechanical fixation of uncoated and HA-coated implants, resulting in a higher shear strength than implants with collagen matrix and control implants. Bone ingrowth and bone formation in the gap were also stimulated 3-fold for OP-1 groups when compared with empty controls, but no difference was found between OP-1 groups and collagen matrix groups. This study suggests that the OP-1 device placed in a gap around uncoated and HA-coated implants is capable of enhancing mechanical fixation and periimplant bone formation. The collagen carrier alone also enhanced bone ongrowth and fixation significantly.

  View details for Web of Science ID 000086458900011

  View details for PubMedID 10794230

• Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Smith, R. L., Lin, J., Trindade, M. C., Shida, J., KAJIYAMA, G., Vu, T., Hoffman, A. R., van der Meulen, M. C., Goodman, S. B., Schurman, D. J., Carter, D. R. 2000; 37 (2): 153-161

  Abstract

  The normal loading of joints during daily activities causes the articular cartilage to be exposed to high levels of intermittent hydrostatic pressure. This study quantified effects of intermittent hydrostatic pressure on expression of mRNA for important extracellular matrix constituents. Normal adult bovine articular chondrocytes were isolated and tested in primary culture, either as high-density monolayers or formed aggregates. Loaded cells were exposed to 10 MPa of intermittent hydrostatic pressure at a frequency of 1 Hz for periods of 2, 4, 8, 12, and 24 hrs. Other cells were intermittently loaded for a period of 4 hrs per day for 4 days. Semiquantitative reverse transcription polymerase chain reaction assays were used to assess mRNA signal levels for collagen types II and I and aggrecan. The results showed that type II collagen mRNA signal levels exhibited a biphasic pattern, with an initial increase of approximately five-fold at 4 and 8 hrs that subsequently decreased by 24 hrs. In contrast, aggrecan mRNA signal increased progressively up to three-fold throughout the loading period. Changing the loading profile to 4 hrs per day for 4 days increased the mRNA signal levels for type II collagen nine-fold and for aggrecan twenty-fold when compared to unloaded cultures. These data suggest that specific mechanical loading protocols may be required to optimally promote repair and regeneration of diseased joints.

  View details for Web of Science ID 000165733400008

  View details for PubMedID 10850821

• Untitled JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Goodman, S. B. 2000; 82A (2): 289

  View details for DOI 10.2106/00004623-200002000-00015

  View details for Web of Science ID 000085208600015

  View details for PubMedID 10682736

• The effect of a silane coupling agent on the bond strength of bone cement and cobalt-chrome alloy JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Yerby, S. A., Paal, A. F., Young, P. M., Beaupre, G. S., Ohashi, K. L., Goodman, S. 2000; 49 (1): 127-133

  Abstract

  Debonding of the cement-implant interface has been hypothesized to be the leading initial indicator of failed total hip prostheses. Many attempts have been made to increase the bond strength of this interface by precoating the implant, increasing the implant's surface roughness, and creating macro-grooves or channels on the implant. However, each of these approaches introduces new complications. This study introduces a unique silane coupling agent used to chemically bond the bone cement to the implant. Cylindrical cobalt-chrome samples were treated with the silane coupling agent, bonded to polymethylmethacrylate, and pushed out to failure. The mean shear strengths were compared to the failure strengths of untreated samples. Half of the specimens were tested immediately following cement curing, and the other half were tested after immersion in saline solution for 60 days. The mean shear strength of the silane-coated samples ranged from 18.2 to 24.1 MPa, and the mean shear strength of the uncoated samples ranged from 7.6 to 15.0 MPa. The increase in strength following silane coating noted in this study may increase the longevity of the implant by decreasing debonding at the interface and, therefore, subsequent failure due to loosening.

  View details for Web of Science ID 000083956000016

  View details for PubMedID 10559755

• Effects of shear stress on articular chondrocyte metabolism 1st International Symposium on Mechanobiology - Cartilage and Chondrocyte Smith, R. L., Trindade, M. C., Ikenoue, T., Mohtai, M., Das, P., Carter, D. R., Goodman, S. B., Schurman, D. J. IOS PRESS. 2000: 95–107

  Abstract

  The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function. Osteoarthritic cartilage often exhibits increased amounts of type I collagen and synthesis of proteoglycans characteristic of immature cartilage. The shift in cartilage phenotype in response to altered load yields a matrix that fails to support normal joint function. Mathematical modeling and experimental studies in animal models confirm an association between altered loading of diarthrotic joints and arthritic changes. Both types of studies implicate shear forces as a critical component in the destructive profile. The severity of cartilage destruction in response to altered loads appears linked to expression of biological factors influencing matrix integrity and cellular metabolism. Determining how shear stress alters chondrocyte metabolism is fundamental to understanding how to limit matrix destruction and stimulate cartilage repair and regeneration. At present, the precise biochemical and molecular mechanisms by which shear forces alter chondrocyte metabolism from a normal to a degenerative phenotype remain unclear. The results presented here address the hypothesis that articular chondrocyte metabolism is modulated by direct effects of shear forces that act on the cell through mechanotransduction processes. The purpose of this work is to develop critical knowledge regarding the basic mechanisms by which mechanical loading modulates cartilage metabolism in health and disease. This presentation will describe the effects of using fluid induced shear stress as a model system for stimulation of articular chondrocytes in vitro. The fluid induced shear stress was applied using a cone viscometer system to stimulate all the cells uniformly under conditions of minimal turbulence. The experiments were carried using high-density primary monolayer cultures of normal and osteoarthritic human and normal bovine articular chondrocytes. The analysis of the cellular response included quantification of cytokine release, matrix metalloproteinase expression and activation of intracellular signaling pathways. The data presented here show that articular chondrocytes exhibit a dose- and time-dependent response to shear stress that results in the release of soluble mediators and extracellular matrix macromolecules. The data suggest that the chondrocyte response to mechanical stimulation contributes to the maintenance of articular cartilage homeostasis in vivo.

  View details for Web of Science ID 000088104400010

  View details for PubMedID 10912182

• Outcome of total hip arthroplasty in small-proportioned patients JOURNAL OF ARTHROPLASTY Rahimtoola, Z. O., Finger, S., Imrie, S., Goodman, S. B. 2000; 15 (1): 27-34

  Abstract

  In a prospective, consecutive series, 41 total hip arthroplasties were performed in 27 small-proportioned patients with small femoral dimensions. The 17 female and 10 male patients averaged 23.6 years (range, 14-47 years), and the mean height and weight were 157 cm (range, 132-183 cm) and 53.5 kg (range, 36-84 kg). The most common preoperative diagnosis was juvenile rheumatoid arthritis in 18 patients (28 hips). Most patients were severely disabled in their daily activity, and 68% of the patients were classified as Charnley functional class C. The femoral implants consisted primarily of the proximally porous-coated miniature Anatomic Medullary Locking femoral component (AML/CDH, Depuy, Warsaw, IN) in 33 hips in 22 patients (average stem diameter, 9.5 mm; range, 8-12.0 mm). A porous ingrowth acetabular cup fixed with screws was used in all procedures. At an average follow-up of 51 months, Harris Hip Scores improved significantly from 34 points (range, 0-65 points) preoperatively to 85 points (range, 33-100 points) after arthroplasty. There were no intraoperative complications. There was 1 revision because of femoral implant loosening. Three cementless femoral components showed evidence of nonprogressive subsidence. One patient had significant bilateral acetabular component polyethylene wear and underwent revision. All other femoral and acetabular components were radiographically stable. The relief of pain and improvement of function were dramatic. The miniature AML/CDH femoral component, combined with an uncemented acetabular cup, provides a promising, off-the-shelf alternative in small-proportioned patients.

  View details for PubMedID 10654459

• The characterization of macrophages and osteoclasts in tissues harvested from revised total hip prostheses JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Chun, L., Yoon, J., Song, Y., Huie, P., Regula, D., Goodman, S. 1999; 48 (6): 899-903

  Abstract

  The differentiation and maturation of macrophages and osteoclasts at the prosthetic interface in cases of implant loosening are poorly understood. Using histochemical and immunohistochemical staining methods, we compare macrophage differentiation in tissues from revised hip replacements in patients with specific clinical-radiological appearances. Periprosthetic tissues were harvested from 12 cemented acetabular and 12 cemented femoral components in 24 patients undergoing revision hip replacement. The prostheses were all radiographically and clinically loose. Six acetabular and six femoral components demonstrated radiographic ballooning osteolysis. Serial 6 microm frozen sections of the periprosthetic tissues were processed with hematoxylin and eosin for general tissue morphology, and analyzed for the presence of tartrate resistant acid phosphatase (TRAP, an osteoclast marker). Immunoperoxidase staining using monoclonal antibodies to CD68 (macrophages and osteoclasts) and CD51 (the alpha chain of the vitronectin receptor, an osteoclast marker) was also performed. Approximately 8-30% of the total cells in the tissues were positive for TRAP and the vitronectin receptor, and comprised a subset of the CD68 positive macrophages and macrophage polykaryons. However, there were no statistically significant differences between specific groups (femoral vs. acetabular, osteolysis vs. no osteolysis) for the numbers or percentages of macrophages or osteoclast-like cells. Once prosthetic loosening has occurred, few differences in the macrophage-osteoclast profile of tissues from different periprosthetic locations, with and without osteolysis, are noted. This suggests a final common biologic pathway for periprosthetic bone resorption, once implant loosening has transpired.

  View details for PubMedID 10556857

• Symptomatic multifocal osteonecrosis - A multicenter study CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Mont, M. A., Jones, L. C., LaPorte, D. M., Aaron, R. K., Christie, M. J., Glueck, C. J., Goodman, S. B., Haas, S., Healy, W. L., Heck, D. A., Holt, P. A., Hungerford, D. S., Iorio, R., Jones, J. P., Klibanoff, J., Lavernia, C. J., Le, T., Lennox, D. W., Levy, R. N., Petri, M., Rifai, A., Rosenberg, A. G., Rosenwasser, M. P., Stauffer, R. N., Steinberg, M. E., Stulberg, B. N., Tsao, A., Urbaniak, J., Vail, T. P., Wang, G. J., Zelicof, S. B., Zizic, T. M. 1999: 312-326

  View details for Web of Science ID 000084102600034

• Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro 44th Annual Meeting of the Orthopaedic-Research-Society Trindade, M. C., Nakashima, Y., Lind, M., Sun, D. H., Goodman, S. B., Maloney, W. J., Schurman, D. J., Smith, R. L. JOHN WILEY & SONS INC. 1999: 797–802

  Abstract

  The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocyte-macrophage colony-stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particle-induced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.

  View details for PubMedID 10632444

• Effects of TGF beta on bone ingrowth in the presence of polyethylene particles JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Goodman, S. B., Song, Y., Chun, L., Regula, D., Aspenberg, P. 1999; 81B (6): 1069-1075

  Abstract

  We implanted bone harvest chambers (BHCs) bilaterally in ten mature male New Zealand white rabbits. Polyethylene particles (0.3+/-0.1 microm in diameter, 6.4 x 10(12) particles/ml) were implanted for two, four or six weeks bilaterally in the BHCs, with subsequent removal of the ingrown tissue after each treatment. In addition to the particles, one side also received 1.5 microg of recombinant transforming growth factor beta1 (TGFbeta1). At two weeks, the bone area as a percentage of total area was less in chambers containing TGFbeta compared with those with particles alone (7.8+/-1.3% v 16.9+/-2.7% respectively; 95% confidence interval (CI) for difference -14.0 to -4.30; p = 0.002). At four weeks, the percentage area of bone was greater in chambers containing TGFbeta compared with those with particles alone (31.2+/-3.4% v 22.5+/-2.0% respectively; 95% CI for difference 1.0 to 16.4; p = 0.03). There were no statistical differences at six weeks, despite a higher mean value with TGFbeta treatment (38.2+/-3.9% v 28.8 +/-3.5%; 95% CI for difference -4.6 to 23.3; p = 0.16). The number of vitronectin-receptor-positive cells (osteoclast-like cells) was greater in the treatment group with TGFbeta compared with that with particles alone; most of these positive cells were located in the interstitium, rather than adjacent to bone. TGFbeta1 is a pleotropic growth factor which can modulate cellular events in the musculoskeletal system in a time- and concentration-dependent manner. Our data suggest that there is an early window at between two and six weeks, in which TGFbeta may favourably affect bone ingrowth in the BHC model. Exogenous growth factors such as TGFbeta may be a useful adjunct in obtaining osseointegration and bone ingrowth, especially in revisions when there is compromised bone stock and residual particulate debris.

  View details for Web of Science ID 000083678200027

• Effects of TGFbeta on bone ingrowth in the presence of polyethylene particles. journal of bone and joint surgery. British volume Goodman, S. B., Song, Y., Chun, L., Regula, D., Aspenberg, P. 1999; 81 (6): 1069-1075

  Abstract

  We implanted bone harvest chambers (BHCs) bilaterally in ten mature male New Zealand white rabbits. Polyethylene particles (0.3+/-0.1 microm in diameter, 6.4 x 10(12) particles/ml) were implanted for two, four or six weeks bilaterally in the BHCs, with subsequent removal of the ingrown tissue after each treatment. In addition to the particles, one side also received 1.5 microg of recombinant transforming growth factor beta1 (TGFbeta1). At two weeks, the bone area as a percentage of total area was less in chambers containing TGFbeta compared with those with particles alone (7.8+/-1.3% v 16.9+/-2.7% respectively; 95% confidence interval (CI) for difference -14.0 to -4.30; p = 0.002). At four weeks, the percentage area of bone was greater in chambers containing TGFbeta compared with those with particles alone (31.2+/-3.4% v 22.5+/-2.0% respectively; 95% CI for difference 1.0 to 16.4; p = 0.03). There were no statistical differences at six weeks, despite a higher mean value with TGFbeta treatment (38.2+/-3.9% v 28.8 +/-3.5%; 95% CI for difference -4.6 to 23.3; p = 0.16). The number of vitronectin-receptor-positive cells (osteoclast-like cells) was greater in the treatment group with TGFbeta compared with that with particles alone; most of these positive cells were located in the interstitium, rather than adjacent to bone. TGFbeta1 is a pleotropic growth factor which can modulate cellular events in the musculoskeletal system in a time- and concentration-dependent manner. Our data suggest that there is an early window at between two and six weeks, in which TGFbeta may favourably affect bone ingrowth in the BHC model. Exogenous growth factors such as TGFbeta may be a useful adjunct in obtaining osseointegration and bone ingrowth, especially in revisions when there is compromised bone stock and residual particulate debris.

  View details for PubMedID 10615988

• Interferon-gamma exacerbates polymethylmethacrylate particle-induced interleukin-6 release by human monocyte/macrophages in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Trindade, M. C., Lind, M., Goodman, S. B., Maloney, W. J., Schurman, D. J., Smith, R. L. 1999; 47 (1): 1-7

  Abstract

  Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. In addition, other immunologic agents, such as interferon-gamma, are present in tissues harvested from the bone-implant interface of failed orthopedic implants. The present study examined the effects of interferon-gamma on polymethylmethacrylate (PMMA) particle-challenged monocyte/macrophages in vitro. The effects of interferon-gamma were determined by measuring interleukin-6 and tumor necrosis factor-alpha release by primary human monocyte/macrophages following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. The interleukin-6 release in response to PMMA particle challenge was stimulated by 76% and 127% in the presence of 1.0 and 10.0 ng/mL of interferon-gamma, respectively. Interferon-gamma challenge alone did not alter interleukin-6 release relative to controls. In contrast to interleukin-6, interferon-gamma challenge stimulated tumor necrosis factor-alpha release in a dose-dependent manner. In the presence of particles, addition of 1.0 and 10.0 ng/mL of interferon-gamma resulted in 17% and 171% increases in the levels of tumor necrosis factor-alpha release, respectively, relative to cultures challenged solely with particles. Blocking antibody to IFN-gamma inhibited the effect of IFN-gamma on particle-induced interleukin-6 and tumor necrosis factor-alpha release. The data presented in this study demonstrate that the immunologic modulator interferon-gamma exacerbates monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.

  View details for PubMedID 10400874

• Proinflammatory mediator release in response to particle challenge: Studies using the bone harvest chamber JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Trindade, M. C., Song, Y., Aspenberg, P., Smith, R. L., Goodman, S. B. 1999; 48 (4): 434-439

  Abstract

  This study reports on the effects of phagocytosable particles on proinflammatory mediator release in an animal model. Bone harvest chambers (BHCs) were implanted bilaterally into mature rabbits; phagocytosable ultrahigh molecular weight polyethylene (UHMWPE) and polystyrene (PS) particles, and the carrier sodium hyaluronate (HE) were tested for their ability to stimulate proinflammatory mediator release. Tissues were harvested after 3, 4, or 6 weeks. Retrieved tissues were placed into culture medium. The release of the proinflammatory mediators interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) into the culture medium was assessed using bioassays. DNA content and dry weights were also measured. The maximal biological response to the PE particles with respect to TNF-alpha and IL-1beta was observed at three weeks with 11- and fivefold stimulations over controls, respectively. The maximal response to PE particles with respect to IL-6 was observed at 4 weeks with a twofold stimulation over controls. Similar patterns were seen with PS particles; however, PE particles stimulated higher cytokine release. PE particles stimulated the expression of IL-1beta, IL-6, and TNF-alpha in the BHC model. Cell culture and human retrieval studies also implicate these proinflammatory mediators in loosening and osteolysis of total joint replacements. Thus, the BHC is a useful in vivo model to document the effects of particles on the evolution of biological responses to particulate debris.

  View details for PubMedID 10421684

• Chemotaxis and activation of particle-challenged human monocytes in response to monocyte migration inhibitory factor and C-C chemokines JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Lind, M., Trindade, M. C., Nakashima, Y., Schurman, D. J., Goodman, S. B., Smith, R. L. 1999; 48 (3): 246-250

  Abstract

  Cytokines that regulate monocyte migration were found in membrane tissue surrounding loosened prosthetic implants. Monocyte migration inhibition factor (MIF) is able to inhibit macrophage migration. Monocyte chemoattractant protein (MCP) and macrophage inflammatory protein (MIP) are potent macrophage chemoattractants. These cytokines may be expressed as part of the foreign body response to prosthetic particulate debris. Chemotaxis analysis and macrophage activation experiments were performed to determine the effects of MIF, MCP-1, and MIP-1alpha on macrophage migration and activation in vitro. We demonstrated that MIF had its maximal migration inhibitory effect for unchallenged and particle challenged macrophages at 1 ng/mL. MCP-1 and MIP-1alpha stimulated macrophage chemotaxis maximally at 1 to 10 ng/mL. Dose-response studies with MIF, MCP-1, and MIP-1alpha demonstrated that these cytokines did not modulate activation of unchallenged or particle challenged macrophages as evaluated by IL-6 and TNF-alpha release. However, these cytokines do not appear to affect macrophage release of proinflammatory mediators in vitro.

  View details for PubMedID 10398027

• Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro. journal of bone and joint surgery. American volume Nakashima, Y., Sun, D. H., Trindade, M. C., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 1999; 81 (5): 603-615

  Abstract

  Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signaling pathways involved in particle-mediated release of cytokines.Macrophages were isolated from mononuclear leukocytes obtained from healthy human donors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes collected at revision total joint arthroplasties and then enzymatically prepared. The experimental protocols included examination of the effects of the inhibition of phagocytosis and the binding of antibodies to macrophage complement receptors on particle-induced macrophage activation. The release of the proinflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) was used to assess macrophage activation. The signaling pathways involved in the induction of cytokine release were analyzed by identification of phosphorylated proteins with use of the Western blot technique and by translocation of the transcription factors nuclear factor-kappa B (NF-kappaB) and nuclear factor-interleukin-6 (NF-IL-6) into the nuclear protein fraction with use of electrophoretic mobility shift assays. The role of serine/threonine and tyrosine kinase pathways in the activation of nuclear factors and the release of cytokines was examined with use of selective pharmacological agents.Exposure of macrophages to titanium-alloy particles in vitro for forty-eight hours resulted in a fortyfold increase in the release of TNF-alpha and a sevenfold increase in the release of IL-6 (p<0.01). Phagocytosis of particles occurred in approximately 73 percent of the macrophages within one hour of exposure. Pretreatment of the macrophages with cytochalasin B reduced phagocytosis by 95 percent but did not reduce the release of TNF-alpha or IL-6. Thus, phagocytosis of particles was not necessary for induction of the release of TNF-alpha or IL-6 in the cultured macrophages. Ligation of the macrophage CD11b/CD18 receptors by integrin-specific antibodies also increased the release of TNF-alpha and IL-6. Antibodies to CD11b/ CD18 receptors (macrophage Mac-1 receptors) reduced phagocytosis of particles by 50 percent (p<0.05). (The CD11b/CD18 macrophage receptor is the macrophage receptor for the complement component CR3bi. The CD11b/CD18 macrophage receptor can also bind to ICAM-1 and ICAM-2. CD is the abbreviation for cluster of differentiation, and ICAM is the abbreviation for intercellular adhesion molecule.) Inhibition of phagocytosis was not accompanied by a decrease in the release of TNF-alpha and IL-6. Blocking RNA synthesis with actinomycin D or preventing protein synthesis with cycloheximide abolished or decreased particle-induced release of TNF-alpha and IL-6 from the macrophages. Macrophage release of TNF-alpha and IL-6 in response to particles coincided with increased tyrosine phosphorylation and mitogen-activated protein kinase activation. Inhibition of tyrosine and serine/threonine kinase activity decreased the particle-induced release of cytokines. Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-kappaB and NF-IL-6. Inhibition of particle phagocytosis did not block activation of the transcription factors. However, inhibition of tyrosine and serine/threonine kinase activity decreased the activation of NF-kappaB and NF-IL-6.These data suggest that particle induced macrophage release of TNF-alpha and IL-6 does not require phagocytosis but is dependent on tyrosine and serine/threonine kinase activity culminating in activation of

  View details for PubMedID 10360689

• Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Nakashima, Y., Sun, D. H., Trindade, M. C., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 1999; 81A (5): 603-615

  Abstract

  Loosening of the implant after total joint arthroplasty remains a serious problem. The activation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signaling pathways involved in particle-mediated release of cytokines.Macrophages were isolated from mononuclear leukocytes obtained from healthy human donors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes collected at revision total joint arthroplasties and then enzymatically prepared. The experimental protocols included examination of the effects of the inhibition of phagocytosis and the binding of antibodies to macrophage complement receptors on particle-induced macrophage activation. The release of the proinflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) was used to assess macrophage activation. The signaling pathways involved in the induction of cytokine release were analyzed by identification of phosphorylated proteins with use of the Western blot technique and by translocation of the transcription factors nuclear factor-kappa B (NF-kappaB) and nuclear factor-interleukin-6 (NF-IL-6) into the nuclear protein fraction with use of electrophoretic mobility shift assays. The role of serine/threonine and tyrosine kinase pathways in the activation of nuclear factors and the release of cytokines was examined with use of selective pharmacological agents.Exposure of macrophages to titanium-alloy particles in vitro for forty-eight hours resulted in a fortyfold increase in the release of TNF-alpha and a sevenfold increase in the release of IL-6 (p<0.01). Phagocytosis of particles occurred in approximately 73 percent of the macrophages within one hour of exposure. Pretreatment of the macrophages with cytochalasin B reduced phagocytosis by 95 percent but did not reduce the release of TNF-alpha or IL-6. Thus, phagocytosis of particles was not necessary for induction of the release of TNF-alpha or IL-6 in the cultured macrophages. Ligation of the macrophage CD11b/CD18 receptors by integrin-specific antibodies also increased the release of TNF-alpha and IL-6. Antibodies to CD11b/ CD18 receptors (macrophage Mac-1 receptors) reduced phagocytosis of particles by 50 percent (p<0.05). (The CD11b/CD18 macrophage receptor is the macrophage receptor for the complement component CR3bi. The CD11b/CD18 macrophage receptor can also bind to ICAM-1 and ICAM-2. CD is the abbreviation for cluster of differentiation, and ICAM is the abbreviation for intercellular adhesion molecule.) Inhibition of phagocytosis was not accompanied by a decrease in the release of TNF-alpha and IL-6. Blocking RNA synthesis with actinomycin D or preventing protein synthesis with cycloheximide abolished or decreased particle-induced release of TNF-alpha and IL-6 from the macrophages. Macrophage release of TNF-alpha and IL-6 in response to particles coincided with increased tyrosine phosphorylation and mitogen-activated protein kinase activation. Inhibition of tyrosine and serine/threonine kinase activity decreased the particle-induced release of cytokines. Exposure of macrophages to either titanium-alloy particles or to antibodies to the receptor proteins CD11b and CD18 for thirty minutes activated the transcription factors NF-kappaB and NF-IL-6. Inhibition of particle phagocytosis did not block activation of the transcription factors. However, inhibition of tyrosine and serine/threonine kinase activity decreased the activation of NF-kappaB and NF-IL-6.These data suggest that particle induced macrophage release of TNF-alpha and IL-6 does not require phagocytosis but is dependent on tyrosine and serine/threonine kinase activity culminating in activation of

  View details for Web of Science ID 000080412800003

• Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles. journal of bone and joint surgery. British volume Nakashima, Y., Sun, D. H., Trindade, M. C., Chun, L. E., Song, Y., Goodman, S. B., Schurman, D. J., Maloney, W. J., Smith, R. L. 1999; 81 (1): 155-162

  Abstract

  Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.

  View details for PubMedID 10068024

• Induction of macrophage C-C chemokine expression by titanium alloy and bone cement particles JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Nakashima, Y., Sun, D. H., Trindade, M. C., Chun, L. E., Song, Y., Goodman, S. B., Schurman, D. J., Maloney, W. J., Smith, R. L. 1999; 81B (1): 155-162

  Abstract

  Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1alpha), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration. We observed MCP-1 and MIP-1alpha expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1alpha in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1alpha were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1alpha inhibited chemotactic activity of the culture medium samples. Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.

  View details for Web of Science ID 000080737900033

• Expression of inflammatory mediators by human macrophages in response to particulate debris in vitro 28th Annual Meeting of the Japanese-Society-for-Replacement-Arthroplasty Nakashima, Y., Sun, D. H., Trindade, M., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L., Ushijima, M., Iwamoto, Y. SPRINGER-VERLAG TOKYO. 1999: 65–75

  View details for Web of Science ID 000086113200007

• Osseointegration of total hip arthroplasties: Studies in humans and animals JOURNAL OF LONG-TERM EFFECTS OF MEDICAL IMPLANTS Song, Y., Beaupre, G., Goodman, S. B. 1999; 9 (1-2): 77-112

  Abstract

  Total hip replacement is a successful, time-proven surgical procedure for reconstruction of the arthritic hip joint. The state of the bone-implant interface is crucial to the long-term integration and durability of hip replacements whether cemented or cementless. This review summarizes current clinical implant retrieval and animal research in hip-joint reconstruction. Future research must attempt to extend the longevity of hip replacements to avoid complex revision surgery.

  View details for PubMedID 10537590

• Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture. journal of bone and joint surgery. British volume Lind, M., Trindade, M. C., Yaszay, B., Goodman, S. B., Smith, R. L. 1998; 80 (5): 924-930

  Abstract

  The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts. In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-alpha was similar in cocultures and in macrophage cultures. IL-1beta release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures. Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes.

  View details for PubMedID 9768911

• Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Lind, M., Trindade, M. C., Yaszay, B., Goodman, S. B., Smith, R. L. 1998; 80B (5): 924-930

  Abstract

  The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1beta), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts. In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-alpha was similar in cocultures and in macrophage cultures. IL-1beta release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures. Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes.

  View details for Web of Science ID 000077389000034

• Prediction of postoperative knee flexion in Insall-Burstein II total knee arthroplasty CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Schurman, D. J., Matityahu, A., Goodman, S. B., Maloney, W., Woolson, S., Shi, H., Bloch, D. A. 1998: 175-184

  Abstract

  Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis.

  View details for PubMedID 9728172

• Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro. journal of bone and joint surgery. British volume Nakashima, Y., Sun, D. H., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 1998; 80 (4): 694-700

  Abstract

  We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 microm in size. Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle. Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.

  View details for PubMedID 9699840

• Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Nakashima, Y., Sun, D. H., Maloney, W. J., Goodman, S. B., Schurman, D. J., Smith, R. L. 1998; 80B (4): 694-700

  Abstract

  We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 microm in size. Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle. Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.

  View details for Web of Science ID 000074909800030

• In vitro, in vivo, and tissue retrieval studies on particulate debris CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Lind, M., Song, Y., Smith, R. L. 1998: 25-34

  Abstract

  The biologic effects of wear debris are an important factor limiting the longevity of total joint replacements. In vivo, in vitro, and tissue retrieval studies have underlined a central role for the macrophage in the etiology of loosening and periprosthetic osteolysis. Wear particles from the materials used for total joint replacement activate macrophages to secrete proinflammatory factors. Complex interactions between macrophages and other cells stimulate bone resorption and suppress bone formation at the prosthetic interface. To improve the long term outcome of joint replacements, future research must find innovative approaches to minimize the production and biologic effects of wear debris.

  View details for PubMedID 9678030

• Effects of polyethylene particles on tissue surrounding knee arthroplasties in rabbits JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Sacomen, D., Smith, R. L., Song, Y., Fornasier, V., Goodman, S. B. 1998; 43 (2): 123-130

  Abstract

  Clinical studies suggest a role for polyethylene (PE) wear debris in the pathogenesis of osteolysis and loosening of total joint replacements. In this study, submicron particles of ultrahigh molecular weight PE (UHMWPE) were placed around pressfit tibial hemiarthroplasties in rabbits to determine the biological reaction. After 6 months the periprosthetic tissue was harvested and characterized biochemically by measuring the extracellular matrix macromolecules, collagen, and glycosaminoglycan (GAG) and quantifying the expression of inflammatory/osteolytic mediators [prostaglandin E2 (PGE2), hexosaminidase, transforming growth factor beta (TGF beta), and interleukins-6 and -1 (IL-6, IL-1)]. Particle exposure resulted in a decrease in levels of total extracellular matrix molecules including a 53% decrease in total GAG (p < 0.05) and a 74% decrease in total collagen (p < 0.005). Collagen content remained significantly decreased when normalized for cellularity (DNA content). Total TGF beta release exhibited a downward trend (p = 0.06) in the particle exposed group. Hexosaminidase and PGE2 levels did not show a difference between groups; however, when normalized for cellularity, PGE2 values exhibited an upward trend in the particle exposed group (p = 0.1). IL-6 was undetected by bioassay and ELISA. Previous studies emphasized that PE debris enhances the degradation of bone. The data from this in vivo model suggest that submicron UHMWPE particles may also act to inhibit biosynthetic pathways of bone and mesenchymal tissue. Decreased levels of collagen, GAG, and TGF beta expression may indicate suppression of bone formation, possibly through a downregulation of osteoblast activity.

  View details for PubMedID 9619430

• Inducible nitric oxide synthase messenger RNA levels in hip periprosthetic tissue: A preliminary study JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Pearson, M. L., Goodman, S. B., Huie, P., Sibley, R. K. 1998; 40 (3): 419-424

  Abstract

  Nitric oxide (NO) is a ubiquitous molecule that has been associated with inflammation, arthritis, autoimmune disease, bone resorption, and other biological processes. Elucidating the role of NO at the bone-implant interface may further our understanding of the biological processes of osseointegration, loosening, and osteolysis. This study demonstrates the use of a molecular biological technique to investigate the possible role of NO in prosthetic loosening and periprosthetic bone resorption following total hip arthroplasty. Periprosthetic tissue from 12 patients undergoing revision hip arthroplasty was harvested and total ribonucleic acid (RNA) was extracted. In six of the 12 patients, multiple samples from different anatomic locations along the same interface were studied. To estimate the amount of NO present in the tissues in vivo, the level of inducible NO synthase (iNOS) messenger RNA (mRNA) was determined using a ribonuclease (RNase) protection assay. Inducible NOS mRNA was detected in every tissue sample: there was no correlation between iNOS mRNA levels and clinical loosening or osteolysis. Analysis of multiple tissue samples from the same prosthetic component revealed that the levels of iNOS mRNA vary greatly, confirming the heterogeneous nature of the interface.

  View details for PubMedID 9570074

• Complex primary and revision total knee arthroplasty using the condylar constrained prosthesis - An average 5-year follow-up JOURNAL OF ARTHROPLASTY Hartford, J. M., Goodman, S. B., Schurman, D. J., Knoblick, G. 1998; 13 (4): 380-387

  Abstract

  The condylar constrained total knee arthroplasty was performed on 29 patients undergoing 33 procedures and were reviewed clinically and radiographically at an average follow-up of 5 years (range, 2-10 years). There were 21 women and 8 men. The average age at the time of surgery was 70 years (range, 32-84). Of the 16 knees that were revision total knee arthroplasties, 8 had a previous infected total knee arthroplasty, and 17 knees had severe deformities requiring the use of the condylar constrained prosthesis. The patients were rated according to the Knee Society clinical and radiological evaluation protocol. Measurements of femoral and tibial component position were obtained as well as femoral tibial angle, patella position, and cement bone radiolucencies. All clinical measurements were made by an independent physical therapist. Clinical results revealed an improvement from an average preoperative knee score of 38 points to an average postoperative score of 86 points. The clinical results for 19 (58%) knees were excellent, 8 (24%) had a good result, 1 (3%) was fair, 2 (6%) were poor, and 3 (9%) were failures. The patients' average functional levels increased from 24 to 58. The final average flexion was 96 degrees. Three knees have been revised (9%). One was revised for recurrent infection, one for periprosthetic fracture, and one for mechanical loosening of the tibial component. There were no other knees with evidence of radiologic loosening. We conclude that the condylar constrained total knee prosthesis provides an acceptable solution for revision and complex primary total knee replacements at an intermediate follow-up term of 5 years.

  View details for PubMedID 9645517

• The use of femoral intramedullary nailing as an interim or salvage technique during complicated total hip replacement JOURNAL OF ARTHROPLASTY Hartford, J. M., Goodman, S. B. 1998; 13 (4): 467-472

  Abstract

  When performing a revision total hip replacement complicated by infection, severe osteolysis, comminuted periprosthetic fracture, and/or extensive bone loss, a single-stage procedure may not be feasible. This study reports four cases of femoral intramedullary nailing as an interim or salvage technique during complicated total hip replacement. This reconstruction provides axial and rotational stability of the femur while maintaining femoral alignment. Furthermore, this reconstruction facilitates early mobilization and rehabilitation of the patient. This interim reconstruction can be converted to a revision total hip replacement at a later time. Alternatively, the stabilized resection arthroplasty may serve as a salvage technique if further reconstruction is not indicated.

  View details for PubMedID 9645530

• The effect of a perioperative clinical pathway for knee replacement surgery on hospital costs ANESTHESIA AND ANALGESIA Macario, A., Horne, M., Goodman, S., Vitez, T., Dexter, F., Heinen, R., Brown, B. 1998; 86 (5): 978-984

  Abstract

  Clinical pathways are being introduced by hospitals to reduce costs and control unnecessary variation in care. We studied 766 inpatients to measure the impact of a perioperative clinical pathway for patients undergoing knee replacement surgery on hospital costs. One hundred twenty patients underwent knee replacement surgery before the development of a perioperative clinical pathway, and 63 patients underwent knee replacement surgery after pathway implementation. As control groups, we contemporaneously studied 332 patients undergoing radical prostatectomy (no clinical pathway in place for these patients) and 251 patients undergoing hip replacement surgery without a clinical pathway (no clinical pathway and same surgeons as patients having knee replacement surgery). Total hospitalization costs (not charges), excluding professional fees, were computed for all patients. Mean (+/-SD) hospital costs for knee replacement surgery decreased from $21,709 +/- $5985 to $17,618 +/- $3152 after implementation of the clinical pathway. The percent decrease in hospitalization costs was 1.56-fold greater (95% confidence interval 1.02-2.28) in the knee replacement patients than in the radical prostatectomy patients and 2.02-fold greater (95% confidence interval 1.13-5.22) than in the hip replacement patients. If patient outcomes (e.g., patient satisfaction) remain constant with clinical pathways, clinical pathways may be a useful tool for incremental improvements in the cost of perioperative care. Implications: Doctors and nurses can proactively organize and record the elements of hospital care results in a clinical pathway, also known as "care pathways" or "critical pathways." We found that implementing a clinical pathway for patients undergoing knee replacement surgery reduced the hospitalization costs of this surgery.

  View details for PubMedID 9585280

• Cellular profile and cytokine production at prosthetic interfaces - Study of tissues retrieved from revised hip and knee replacements JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Goodman, S. B., Huie, P., Song, Y., Schurman, D., Maloney, W., Woolson, S., Sibley, R. 1998; 80B (3): 531-539

  Abstract

  The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces.

  View details for Web of Science ID 000073647500031

• Cellular profile and cytokine production at prosthetic interfaces. Study of tissues retrieved from revised hip and knee replacements. journal of bone and joint surgery. British volume Goodman, S. B., Huie, P., Song, Y., Schurman, D., Maloney, W., Woolson, S., Sibley, R. 1998; 80 (3): 531-539

  Abstract

  The tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation. We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (p = 0.0006), T-lymphocyte subgroups (p = 0.03) and IL-1 (p = 0.02) and IL-6 (p = 0.0001) expression, and in the cementless series with increased numbers of T-lymphocyte subgroups (p = 0.005) and increased TNF alpha expression (p = 0.04). For cemented implants, the histological, histochemical and cytokine profiles of the interface correlated with the clinical and radiological grade of loosening and osteolysis. Our findings suggest that there are different biological mechanisms of loosening and osteolysis for cemented and cementless implants. T-lymphocyte modulation of macrophage function may be an important interaction at prosthetic interfaces.

  View details for PubMedID 9619952

• Total hip arthroplasty in juvenile chronic arthritis - A consecutive series JOURNAL OF ARTHROPLASTY Haber, D., Goodman, S. B. 1998; 13 (3): 259-265

  Abstract

  Twenty-nine total hip arthroplasties in 16 patients with juvenile chronic arthritis were performed by one surgeon and followed prospectively. The 9 female and 7 male patients averaged 21 years of age (range, 14-35). Height and weight averaged 160 cm (63 inches) and 53 kg (118 lb.), respectively. Preoperative planning used small or miniature components to accommodate the small anatomic proportions of the hip. The femoral component was cementless in the majority (20/29), but required cementing in 10 of 29 hips because of poor bone stock. The acetabula were reconstructed with a porous-coated cup with or without screws (27/29) or with a cemented cup (2/29). Follow-up periods averaged 53 months (range, 24-100 months). The average Harris hip score improved from 37 to 78 after surgery (P = .0001). Pain relief was excellent; 15 of 16 patients (27/29 hips) expressed a significant improvement in daily function and lifestyle, despite systemic involvement of their arthritis. The range of motion of the hip improved significantly in all planes (P = .001). Two of the 4 uncemented Muller CDH components (Protek, Bern, Switzerland) with a large offset have migrated into varus; both are pain-free. One cemented femoral component has been revised because of aseptic loosening. The use of a small or miniature, cemented or cementless femoral component and a porous-coated cup appears to provide an excellent method of hip reconstruction for patients with juvenile chronic arthritis and small anatomic proportions; however, a femoral component with too great an offset should be avoided, because this may result in varus migration of the stem.

  View details for PubMedID 9590636

• Norian SRS cement augmentation in hip fracture treatment - Laboratory and initial clinical results CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Bauer, T. W., Carter, D., Casteleyn, P. P., Goldstein, S. A., Kyle, R. F., Larsson, S., Stankewich, C. J., Swiontkowski, M. F., Tencer, A. F., Yetkinler, D. N., Poser, R. D. 1998: 42-50

  Abstract

  Bone quality, initial fracture displacement, severity of fracture comminution, accuracy of fracture reduction, and the placement of the internal fixation device are important factors that affect fixation stability. New high strength cements that are susceptible to remodeling and replacement for fracture fixation may lead to improved clinical outcome in the treatment of hip fractures. Norian SRS is an injectable, fast setting cement that cures in vivo to form an osteoconductive carbonated apatite of high compressive strength (55 MPa) with chemical and physical characteristics similar to the mineral phase of bone. It can be used as a space filling internal fixation device to facilitate the geometric reconstruction, load transfer, and healing of bone with defects and/or fractures in regions of cancellous bone. Furthermore, this cement can improve the mechanical holding strength of conventional fixation devices. Use of this material potentially could improve fracture stability, retain anatomy during fracture healing and improve hip function, thus achieving better clinical outcomes. In vivo animal studies have shown the material's biocompatibility, and cadaveric studies have shown the biomechanical advantage of its use in hip fractures. Initial clinical experience (in 52 femoral neck fractures and 39 intertrochanteric fractures) showed the potential clinical use of this innovative cement in the treatment of hip fractures.

  View details for PubMedID 9553532

• Preoperative duplex ultrasonography evaluation for deep vein thrombosis in hip and knee arthroplasty patients. American journal of orthopedics (Belle Mead, N.J.) Hartford, J. M., JEFFREYS, B., Goodman, S. B. 1998; 27 (2): 123-127

  Abstract

  We performed preoperative and postoperative duplex ultrasonography examinations on both lower extremities in 128 patients undergoing 146 hip and knee reconstructive procedures. The results of the examinations were reviewed by an independent radiologist who specializes in these studies. Three of the 128 patients (146 procedures; 2.1%) had evidence of a deep venous thrombosis or other venous abnormality before surgery. Three additional patients developed a deep venous thrombosis after surgery, despite mechanical and pharmacologic prophylaxis. We have discontinued performing preoperative duplex ultrasonography prior to primary, uncomplicated total joint replacement of the lower extremities. We continue to perform duplex ultrasonography before surgery in patients at high risk, with a history of deep venous thrombosis or phlebitic syndrome, and in those who have previously had major surgery on the lower extremities.

  View details for PubMedID 9506197

• Composite hip prosthesis design .2. Simulation JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Yildiz, H., Chang, F. K., Goodman, S. 1998; 39 (1): 102-119

  Abstract

  An investigation was performed to study the mechanical performance of fiber-reinforced composite hip prostheses. In Part I of the study, a three-dimensional finite element code was developed for analyzing a composite hip prosthesis in a femur. The material properties of the composite were treated as anisotropic and inhomogeneous while the properties of the femoral bone were treated as anisotropic and homogeneous. All the materials were assumed to behave linear-elastically. Thermoplastic graphite/PEEK material was selected for the study. No slippage was assumed at the interface between the implant and the surrounding femoral bone. In Part II, numerical simulations were performed using the code to study the performance of a composite prosthesis in the femur. The stress/strain distributions, micromotions, and strain energy density of the surrounding femoral bone were evaluated and found to be related to initial fixation and long-term stability of the prosthesis in the femur. Numerous fiber orientations were studied, and the results of the calculations were compared with those generated from a prosthesis made of cobalt chrome and Ti-6Al-4V titanium alloys. Based on the analysis, it was shown that compared to conventional metallic implants more favorable stresses and deformations could be generated in the femur using composite implants. In addition, by changing fiber orientations according to femoral loads, a composite implant could be designed specifically for the left or the right femur.

  View details for PubMedID 9429102

• Materials in total joint replacement CURRENT ORTHOPAEDICS SANTAVIRTA, S., KONTTINEN, Y. T., Lappalainen, R., Anttila, A., Goodman, S. B., Lind, M., Smith, L., Takagi, M., Gomez-Barrena, E., Nordsletten, L., Xu, J. W. 1998; 12 (1): 51-57

  View details for Web of Science ID 000072909300008

• Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Constantz, B. R., Barr, B. M., Ison, I. C., Fulmer, M. T., Baker, J., McKinney, L. A., Goodman, S. B., Gunasekaren, S., Delaney, D. C., Ross, J., Poser, R. D. 1998; 43 (4): 451-461

  Abstract

  Four calcium phosphate cement formulations were implanted in the rabbit distal femoral metaphysis and middiaphysis. Chemical, crystallographic, and histological analyses were made at 2, 4, and 8 weeks after implantation. When implanted into the metaphysis, part of the brushite cement was converted into carbonated apatite by 2 weeks. Some of the brushite cement was removed by mononuclear macrophages prior to its conversion into apatite. Osteoclastlike cell mediated remodeling was predominant at 8 weeks after brushite had converted to apatite. The same histological results were seen for brushite plus calcite aggregate cement, except with calcite aggregates still present at 8 weeks. However, when implanted in the diaphysis, brushite and brushite plus calcite aggregate did not convert to another calcium phosphate phase by 4 weeks. Carbonated apatite cement implanted in the metaphysis did not transform to another calcium phosphate phase. There was no evidence of adverse foreign body reaction. Osteoclastlike cell mediated remodeling was predominant at 8 weeks. The apatite plus calcite aggregate cement implanted in the metaphysis that was not remodeled remained as poorly crystalline apatite. Calcite aggregates were still present at 8 weeks. There was no evidence of foreign body reaction. Osteoclastlike cell remodeling was predominant at 8 weeks. Response to brushite cements prior to conversion to apatite was macrophage dominated, and response to apatite cements was osteoclast dominated. Mineralogy, chemical composition, and osseous implantation site of these calcium phosphates significantly affected their in vivo host response.

  View details for Web of Science ID 000077259500013

  View details for PubMedID 9855204

• Knee arthroplasty in rheumatoid arthritis - A report from the Swedish Knee Arthroplasty Register on 4,381 primary operations 1985-1995 ACTA ORTHOPAEDICA SCANDINAVICA Robertsson, O., Knutson, K., Lewold, S., Goodman, S., Lidgren, L. 1997; 68 (6): 545-553

  Abstract

  The Swedish Knee Arthroplasty Register has data on 4,381 primary operations performed 1985-1995 for rheumatoid arthritis. Of these, 192 were performed with unicompartmental prostheses and 4143 with tricompartmental. 77% were women and the mean age was 66 years. There were 126 first, 20 second, and 1 third revision in tricompartmental arthroplasties, mainly for loosening, infection and patellar problems. There were 38 first, 3 second, and 1 third revision in unicompartmental arthroplasties, mainly for progression of RA and loosening. Cumulative revision rates (Kaplan-Meier) were calculated. Tricompartmental knees had a 10-year cumulative revision rate of 5% and uni-knees 25%. Patients treated before 1990, men and patients younger than 55 had higher revision rates than patients treated after 1990, women and older patients, respectively. Cemented tibial components resulted in lower revision rates than uncemented ones. There was no significant difference in revision rates between patellar replaced and unreplaced knees or between the 9 commonest implant types.

  View details for Web of Science ID 000071448900009

  View details for PubMedID 9462354

• Stability of open-book pelvic fractures using a new biomechanical model of single-limb stance JOURNAL OF ORTHOPAEDIC TRAUMA MacAvoy, M. C., McClellan, R. T., Goodman, S. B., Chien, C. R., Allen, W. A., van der Meulen, M. C. 1997; 11 (8): 590-593

  Abstract

  A new biomechanical model of single-limb stance was developed to test the stability of intact, injured, and internally fixed pelves.Single-limb stance was simulated by applying muscle forces and body mass loading to cadaver pelves. We created a rotationally unstable "open-book" pelvic injury in nine embalmed pelves by dividing the ligaments of the pubic symphysis, pelvic floor, and anterior and interosseus sacroiliac joint. All pelves were devoid of gross structural abnormalities.Two methods of internal fixation of the pubis symphysis were compared: (a) a curved six-hole 3.5-millimeter reconstruction plate across the superior pubic symphysis, and (b) the same six-hole 3.5-millimeter reconstruction plate plus a perpendicularly oriented four-hole 3.5-millimeter reconstruction plate placed across the anterior symphysis.We measured vertical shear displacement at the public symphysis and horizontal displacement at the anterior sacroiliac joint. The results for the injured and fixed specimens were compared with each other and with the results for the intact specimens.The injured unfixed specimens showed marked instability that was prevented by both methods of fixation of the pubic symphysis. No significant differences could be demonstrated between single and double plating of the disrupted pubic symphysis when using this single-limb stance model.This model of single-limb stance suggests that a single symphyseal plate across the pubic symphysis can stabilize the open-book injury under short-term quasi-static loads.

  View details for PubMedID 9415866

• Economics of a perioperative clinical pathway for knee replacement surgery Macario, A., Vitez, T., Horne, M., Goodman, S., McDonald, T., Woolson, S., Heinen, R., CrawfordSwent, C. LIPPINCOTT WILLIAMS & WILKINS. 1997: A1018

  View details for DOI 10.1097/00000542-199709001-01018

  View details for Web of Science ID A1997XV63601018

• Design of the femoral component for cementless hip replacement: the surgeon's perspective. American journal of orthopedics (Belle Mead, N.J.) Kelsey, D., Goodman, S. B. 1997; 26 (6): 407-412

  Abstract

  Few guidelines are currently available to the surgeon when choosing a specific femoral component for cementless total hip replacement (THR). A survey of the members of the American Association for Hip and Knee Surgeons (AAHKS) was conducted to gain insight into the importance of implant material, stress shielding, and micromotion in the selection of cementless femoral components. A comprehensive survey was distributed to 300 orthopedic surgeons selected from the members of the AAHKS; 169 of the 300 surgeons completed the detailed questionnaire. The results of the survey were analyzed using the SPSS software package to obtain general trends in opinion, and a stepwise regression analysis was used to correlate responses with training and clinical experience. Interestingly, there was little consensus among surgeons with respect to the relative importance of implant material, stress shielding, and micromotion in the selection of prostheses for cementless THR. In general, bone loss secondary to stress shielding was the least important issue, and axial and rotational micromotion were considered progressively more significant problems. Cementless titanium alloy stems were perceived as offering no significant advantage over cobalt chrome alloy stems. Moreover, there was no consensus as to whether a collar was advantageous. Prosthesis stability, restoration of motion, and a proven clinical record were more important to surgeons than were ease of implantation and removal, cost, and availability.

  View details for PubMedID 9193693

• Loosening and osteolysis of cemented joint arthroplasties - A biologic spectrum CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Huie, P., Song, Y., Lee, K., Doshi, A., Rushdieh, B., Woolson, S., Maloney, W., Schurman, D., Sibley, R. 1997: 149-163

  Abstract

  The purpose of this study was to characterize the cell types (using immunohistochemistry) and cytokine expression (using in situ hybridization) of tissues surrounding well fixed and loose cemented prostheses undergoing revision. Clinical and radiographic data were gathered prospectively for a series of cemented total joint replacements undergoing revision. Three groups were identified: (1) loose implants with osteolysis (10 specimens), (2) loose implants without osteolysis (11 specimens), and (3) well fixed implants (7 specimens). At surgery, a specimen was harvested from the bone cement interface. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages and lymphocyte subgroups. Human antisense probes were selected to identify the mRNA for specific cytokines using in situ hybridization. The percentage of positively staining cells was determined for each antibody or probe using a grid counting technique. Tissues from loose cemented prostheses with osteolysis contained significantly greater numbers of macrophages and T lymphocytes compared with tissues from loose and well fixed cemented prostheses without osteolysis. The number of interleukin-1 and interleukin-6 positive cells was highest in specimens with osteolysis and lowest in specimens from well fixed prostheses. These cytokines modulate the growth and differentiation of cells in the immune system and the monocyte and macrophage system and mediate the remodeling of bone and mesenchymal tissues. Specific cell populations and cytokine profiles appear to be involved in periprosthetic osteolysis; this information may be useful in planning strategies for prevention and treatment.

  View details for PubMedID 9137186

• The fibrous tissue interface surrounding well-fixed, revised, cementless acetabular components for hip replacement Symposium on Modularity of Orthopedic Implants Goodman, S. B., Huie, P., Song, Y., OConnor, M., Woolson, S. T., Maloney, W. J., Schurman, D. J., Sibley, R. AMERICAN SOCIETY TESTING AND MATERIALS. 1997: 21–32

  View details for Web of Science ID A1997BH43N00002

• Composite implant for bone replacement JOURNAL OF COMPOSITE MATERIALS Kelsey, D. J., Springer, G. S., Goodman, S. B. 1997; 31 (16): 1593-1632

  View details for Web of Science ID A1997XU85200003

• Polyethylene and titanium alloy particles reduce bone formation - Dose-dependence in bone harvest chamber experiments in rabbits ACTA ORTHOPAEDICA SCANDINAVICA Goodman, S., Aspenberg, P., Song, Y., Regula, D., Lidgren, L. 1996; 67 (6): 599-605

  Abstract

  Particles similar to those generated from joint replacements affect net bone formation within the Bone Harvest Chamber in rabbits. Whether these effects depend on the concentration of particulate materials is unknown. In this study, we performed a histomorphologic and morphometric analysis of net bone formation in the Bone Harvest Chamber in the presence of different concentrations of phagocytosable particles of high density polyethylene and titanium 6-aluminum 4-vanadium alloy. Chambers were implanted in 9 mature New Zealand white rabbits bilaterally. Concentrations of 10(6), 10(7) and 10(8) polyethylene particles/mL, and 10(8) and 10(9) particles/ mL of titanium alloy in 1% sodium hyaluronate carrier were implanted for 3-week periods in sequence in each of the chambers. 3-week control periods in which nothing was implanted in the chamber were included between the treatments. Increasing concentrations of polyethylene particles were associated with a more marked foreign body response and fibrosis. Net bone formation for the three polyethylene doses was reduced by 11%, 21% and 33% of controls, respectively. For titanium alloy, net bone formation was reduced by 8% and 56% of controls, for concentrations of 10(8) and 10(9) particles/mL, respectively. Our findings suggest possible adverse effects of wear debris on net bone formation and bony remodeling in the prosthetic bed, when concentrations of specific particles reach critical local levels.

  View details for PubMedID 9065075

• Tourniquet release: Systemic and metabolic effects ACTA ANAESTHESIOLOGICA SCANDINAVICA Townsend, H. S., Goodman, S. B., Schurman, D. J., Hackel, A., BROCKUTNE, J. G. 1996; 40 (10): 1234-1237

  Abstract

  The pneumatic tourniquet produces ischemic changes in limbs. The effects of tourniquet release on systemic blood pressure and metabolic parameters were studied in 11 adult patients undergoing total knee replacement under general anesthesia. Mean arterial pressure (MAP) decreased rapidly after the release of the tourniquet, becoming significant at 3 min and remaining significantly depressed up to 15 min post release. Arterial pH, PaO2, PaCO2, lactate acid, and potassium changed significantly after the release, but normalized within 30 min. These results are notably different from a previous study in a similar patient population undergoing knee replacement under epidural anesthesia. Compared to patients under epidural anesthesia, patients receiving general anesthesia with mechanical ventilation are unable to compensate for the metabolic load caused by the tourniquet release, as the latter group are unable to alter their ventilatory rate. In elderly patients with decreased cardio-pulmonary reserve, this may be of clinical importance.

  View details for PubMedID 8986188

• Early outcome of total hip arthroplasty using the direct lateral vs the posterior surgical approach ORTHOPEDICS BARBER, T. C., ROGER, D. J., Goodman, S. B., Schurman, D. J. 1996; 19 (10): 873-875

  Abstract

  A consecutive series of 49 patients who had a primary total hip arthroplasty (THA) for osteoarthritis is reviewed to determine the difference in clinical outcome between the direct lateral and the posterior surgical approaches to the hip. Group 1 comprised 28 patients off had THA by the same surgeon using a posterolateral approach. Group 2 comprised 21 patients who had THA using the direct lateral approach, modified from Hardinge. The improvement in the limp, abductor strength, Trendelenburg test, and range of motion over time was similar in the two groups. The average Harris hip score at 1 year was 90 for Group 1 (posterior approach) and Group 2 (lateral approach). At 2-year minimum follow up, the Harris hip score was 94 for both groups. Radiographic review showed that the incidence and severity of heterotopic bone was also similar for both groups. The authors conclude that the clinical and radiographic outcome for THA using the posterior and the lateral approaches to the hip yield similar clinical results.

  View details for PubMedID 8905861

• Histomorphological reaction of bone to different concentrations of phagocytosable particles of high-density polyethylene and Ti-6Al-4V alloy in vivo BIOMATERIALS Goodman, S. B., Davidson, J. A., Song, Y., Martial, N., Fornasier, V. L. 1996; 17 (20): 1943-1947

  Abstract

  Wear debris has been implicated in the pathogenesis of loosening and osteolysis of total joint replacements by stimulating a foreign body and chronic inflammatory reaction capable of bone resorption. Whether increasing concentrations of wear particles have an adverse biological effect on bone has not been elucidated. We performed a histomorphological and semi-quantitative morphometric analysis of the reaction of bone to different concentrations of phagocytosable particles of high-density polyethylene (HDPE) and titanium 6-aluminium 4-vanadium alloy (Ti-6Al-4V) implanted in the rabbit tibia. The Ti-6Al-4V particles had a diameter of 4.0 +/- 4.4 microns (mean +/- SD); the HDPE particles averaged 4.7 +/- 2.1 microns. Suspensions of 10(6)-10(9) particles per ml were mixed in saline, sterilized, and introduced through a drill hole into the proximal tibia of 30 mature female rabbits. Controls included drilled, but non-implantable limbs. The animals were killed at 16 weeks and histological sections were made of the implant area. Histomorphological assessment was carried out using an interactive image analysis system. The parameters assessed included the presence of histiocytes, foreign body giant cells and inflammatory cells, the location and number of particles, the presence of haematopoeitic elements, fat or necrosis of the marrow, whether healing of the cortical window had taken place, and whether there was evidence of formation or resorption of bone by the periosteum, cortex and marrow. A semi-quantitative rating system was employed. Phagocytosable particles of Ti-6Al-4V and HDPE, in concentrations of 10(6)-10(9) particles per ml, evoked a histiocytic reaction without extensive fibrosis, necrosis or granuloma formation. This reaction occurred without disturbing the normal repair processes of bone formation and resorption to the surgical insult. A clear dose-response effect on the histological parameters assessed in this study was not noted. Using the present model, by 16 weeks, a similar "one time' particle load could be accommodated. The ongoing generation of particulate debris over a more extended period of time might be necessary before the remodelling processes of bone would be disturbed.

  View details for PubMedID 8894085

• Different effects of phagocytosable particles during bone formation versus remodeling JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Goodman, S., Aspenberg, P., Song, Y., Regula, D., Lidgren, L. 1996; 33 (3): 153-158

  Abstract

  Previously, small phagocytosable particles of high density polyethylene (HDPE) but not Ti6-Al4-V alloy, at a concentration of 10(8) particles/mL inhibited net bone formation in vivo after 3 weeks in the bone harvest chamber (BHC). These findings reflected the effects of particles during the phase of bone ingrowth. In this study, we tested whether these effects persisted or were different during the phase of bone maturation and remodeling. BHCs were bilaterally implanted in mature male NZW rabbits. After a 6-week period for osseointegration, the contents of the chamber were harvested and discarded. One percent sodium hyaluronate, the carrier, was then placed within the canal of the chambers bilaterally and the tissue within the chambers was harvested 3 weeks later. HDPE particles were then inserted unilaterally for a 3-week period, followed by Ti6-Al4-V for 3 weeks, HDPE for 6 weeks, and Ti6-Al4-V for 6 weeks. The side chosen for each treatment was switched consecutively; the nonimplanted, contralateral chamber served as a control. At 3 weeks the control treatments yielded trabeculae of woven bone in a fibrovascular stroma. By 6 weeks, the peripheral trabeculae were thicker, and a central marrow cavity was developing. Bone ingrowth was less with HDPE particles at 3 and 6 weeks compared to controls. Ti6-Al4-V particles did not inhibit bone ingrowth at 3 weeks but showed a trend at 6 weeks. The characteristics of particles affect the differentiation, maturation, and remodeling of mesenchymal tissue differently.

  View details for PubMedID 8864887

• Heterogeneity in cellular and cytokine profiles from multiple samples of tissue surrounding revised hip prostheses JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Goodman, S. B., Knoblich, G., OConnor, M., Song, Y., Huie, P., Sibley, R. 1996; 31 (3): 421-428

  Abstract

  Previous studies have attempted to define the biologic properties of the bone-implant interface using a single specimen harvested from the periprosthetic tissues. The purpose of this study was to examine the heterogeneity in cellular and cytokine profiles of multiple samples taken from the tissues surrounding revised hip prostheses. Clinical and radiographic data for nine patients undergoing surgical revision was gathered prospectively. Three tissue samples were taken systematically from the acetabular and/or femoral bed. Morphologic characteristics of the tissues were assessed using hematoxylin and eosin-stained sections. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages (EMB11 and CD68); activated macrophages (Leu M3); total T lymphocytes (Leu 4 and T11); T-helper lymphocytes (Leu 3A and CD4); cytotoxic/suppressor T lymphocytes (Leu 2A and CD3); and fibroblasts (5B5). In situ hybridization was used to identify the mRNA for specific proteins: interleukin (IL)1 alpha and -beta, IL-2, IL-6, transforming growth factor beta, tumor necrosis factor alpha (TNF alpha), platelet-derived growth factor alpha (PDGF alpha), and interferon gamma. A quantitative assessment was performed for each section by calculating the percentage of positively staining cells using a light microscope and grid-counting technique. A random effect analysis of variance was calculated to determine both the variance between samples within each patient and the variance between different patients. Standard deviations contributed by sampling variance and patient variance were calculated and an F test was applied. Tissue samples taken from different regions of the bone-prosthesis interface showed marked heterogeneity in cellular and cytokine profiles. Critical F values indicating a statistically significant degree of variance between different tissue samples were exceeded for macrophages, cytotoxic/suppressor T lymphocytes, and T-helper lymphocytes. The cytokine profile was significantly different for IL-2, PDGF alpha, and TNF alpha. This tissue heterogeneity may be due to different mechanical and biologic environments along the bone-prosthesis interface. Thus, caution must be exercised in defining the biologic properties of the tissue surrounding revised prostheses according to a single biopsy.

  View details for PubMedID 8806069

• Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophages in vitro JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Gonzalez, O., Smith, R. L., Goodman, S. B. 1996; 30 (4): 463-473

  Abstract

  This study investigated effects of different sizes, concentrations, volumes, and surface areas of polymethylmethacrylate (PMMA) particles on human macrophages. Adherent peripheral blood monocytes isolated from five healthy individuals were exposed for 48 h to phagocytosable (0.325 micron and 5.5 microns) and nonphagocytosable (200 microns) spherical particles. Each particle size was tested over a range of concentrations (10(4)-10(11) particles per milliliter [0.325 micron], 10(2)-10(7) particles per milliliter [5.5 microns], 10(1)-10(4) particles per milliliter [200 microns]) to provide overlap in number, volume, and surface area. Primary human monocyte/macrophages were cultured in macrophage serum-free medium and 5% fetal calf serum. Macrophage viability was assessed by 3H-thymidine uptake and activation was quantified by release of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2 (PGE2), and the lysosomal enzyme hexosaminidase. Medium alone served as a negative control; lipopolysaccharide (10 micrograms/mL) was also tested. PMMA particles were not toxic to human macrophages at any concentration tested. The smallest phagocytosable particles (0.325 micron) stimulated the release of interleukin-1 beta, interleukin-6, prostaglandin E2, and hexosaminidase at concentrations of 10(10)-10(11) particles/mL. The release of cytokines, PGE2, and hexosaminidase depended on the size, concentration, surface area, and volume of the phagocytosable particles. This study demonstrates that PMMA particle load Mi.e., the concentration of phagocytosable particles per tissue volume, characterized by size, surface area, and volume, rather than simply particle number-determines the degree of macrophage activation.

  View details for PubMedID 8847354

• Benign response to particles of diamond and SiC: Bone chamber studies of new joint replacement coating materials in rabbits BIOMATERIALS Aspenberg, P., Anttila, A., KONTTINEN, Y. T., Lappalainen, R., Goodman, S. B., Nordsletten, L., SANTAVIRTA, S. 1996; 17 (8): 807-812

  Abstract

  Wear particles from total joint replacements are thought to accelerate prosthetic loosening. Diamond coating may improve the smoothness and wear characteristics of the femoral head component of total hip replacements, and thus increase their longevity. The brittleness of a thin diamond coat may be overcome by using an SiC-whisker diamond composite. This study describes the reactions of regenerating bone tissue to phagocytosable particles of diamond and SiC, using implanted bone harvest chambers in rabbits. The particles were dispersed in hyaluronan and introduced into a canal transversing the implant. The tissue that entered the canal during the following 3 weeks was then harvested. In previous studies using this model, particles of high density polyethylene, bone cement and chromium-cobalt all caused an inflammatory reaction and a marked decrease in the amount of ingrown bone. In the present study, neither the diamond nor the SiC particles caused any decrease in bone formation. It appears that particles of diamond and SiC are comparatively harmless.

  View details for Web of Science ID A1996UE60900008

  View details for PubMedID 8730965

• Biomechanical comparison of posterior internal fixation techniques for unstable pelvic fractures JOURNAL OF ORTHOPAEDIC TRAUMA Comstock, C. P., VANDERMEULEN, M. C., Goodman, S. B. 1996; 10 (8): 517-522

  Abstract

  Early reduction and rigid fixation of unstable vertical shear pelvic fractures has been shown to decrease the incidence of late sequelae and facilitate early mobilization. The results of fixation of the posterior pelvic ring without anterior fixation are unknown. The purpose of this study was to perform a biomechanical comparison of the most frequently used techniques of posterior fixation for unstable pelvic sacroiliac dislocations in conjunction with ipsilateral rami fractures, i.e., an unstable vertical shear injury. The four methods of posterior fixation tested included sacroiliac (SI) screws, anterior SI plates, transiliac bars, and a combination of SI screws and transiliac bars. Six cadaveric pelvises were tested in axial compression and torsion on a biaxial servohydraulic testing machine. Compared to the intact pelvis, single posterior methods of fixation provided approximately 70-85% resistance to axial and torsional loading. By combining SI screws with transiliac bars, approximately 90% of intact pelvic stability was achieved. Our results suggest that rigid posterior fixation of sacroiliac dislocations alone may obviate the need for additional complex anterior surgical procedures to fix rami fractures.

  View details for PubMedID 8915911

• Influence of callus deformation time - Bone chamber study in rabbits CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Aspenberg, P., Goodman, S. B., Wang, J. S. 1996: 253-261

  Abstract

  Short periods of strain have effects on tissue differentiation in a skeletal defect. Little is known about the importance of the duration of such periods. The authors compared 2 short daily periods of strain pulses that differed only by their duration. This was done by using the micromotion chamber, which is a titanium implant with a transverse intraosseous canal. Fibrous tissue forms in the canal and then is replaced by bone through membranous (metaplastic) ossification. The tissue in the canal can be exposed to cyclic deformation. The chamber allows harvest of the tissue within the canal without disturbing the outer parts of the implant or the surrounding bone, thus enabling repeated experiments in the same animal. Chambers were inserted in 6 rabbits and repeatedly harvested at 3-week intervals. Between harvests, the chambers were subjected to either no motion, 20 cycles once daily during 20 seconds (1 Hz), or 20 cycles once daily during 120 seconds (0.17 Hz). Altogether 39 harvested specimens were studied. The 20-second treatment tended to increase the amount of ingrown bone as compared with no motion, whereas the 120-second treatment caused a marked decrease in bone formation and increase in fibrous tissue. Because the acute tissue trauma appears similar with both deformation treatments, it would appear that the increased fibrous tissue formation with the longer deformation time is caused by the parameters of tissue deformation and not by increased tissue damage.

  View details for Web of Science ID A1996TP57400030

  View details for PubMedID 8542702

• Does the immune system play a role in loosening and osteolysis of total joint replacements? JOURNAL OF LONG-TERM EFFECTS OF MEDICAL IMPLANTS Goodman, S. B. 1996; 6 (2): 91-101

  Abstract

  Total joint replacement is a highly successful surgical procedure with an excellent outcome over many years. However, because this procedure is now being performed in younger patients, and because the average age of our population continues to increase, greater expectations have been placed on joint implants in the hope that they will last forever. Aseptic loosening and osteolysis of total joint replacements are the main processes limiting long-term implant survival. This paper focuses on the possible role of immunological mechanisms in the processes of loosening and osteolysis of joint replacements, with special emphasis on polymeric materials. This topic is very controversial: In vitro experiments and in vivo studies in animals and humans are reviewed and provide evidence for both sides of the debate. In some patients, immunological processes appear to be activated after a total joint replacement has been implanted. Specific materials or their by-products might function as haptens and elicit a T-lymphocyte-mediated, delayed hypersensitivity reaction. Many factors probably are important, including the genetic makeup and immune competence of the patient, prior exposure to the same or similar materials, degree of exposure (rate of generation of particles and the efficacy of clearance mechanisms), and characteristics of the particles themselves.

  View details for PubMedID 10163512

• Oxford meniscal bearing knee versus the Marmor knee in unicompartmental arthroplasty for arthrosis - A Swedish multicenter survival study JOURNAL OF ARTHROPLASTY Lewold, S., Goodman, S., Knutson, K., Robertsson, O., Lidgren, L. 1995; 10 (6): 722-731

  Abstract

  In the Swedish Knee Arthroplasty Study, all 699 Oxford meniscal bearing cemented unicompartmental prostheses (Biomet, Bridgend, UK) were identified and analyzed regarding failure pattern and compared with all Marmor prostheses (Smith & Nephew Richards, Orthez, France) and with a time-, age-, and sex-matched subset of Marmor prostheses using survival statistics expressed as cumulative revision rates. After 1 year there was already a higher rate, and after 6 years the rate of the Oxford group was more than twice that of the Marmor group. There were 50 revisions in the Oxford group: dislocating meniscus in 16, loosening of the femoral component in 6, tibial component in 4, both components in 4, contralateral arthrosis in 10, infection in 4, and technical failure with instability, pain, and/or impingement of the meniscal bearing anterior in the femoral condyle in 6. It is still unclear if the design with the sliding menisci will, in the long turn, reduce wear and loosening, thereby compensating for the initially inferior results. It is recommended that until this question is clarified, the Oxford knee should be used on a limited scale for long-term comparative studies only.

  View details for Web of Science ID A1995TL44800003

  View details for PubMedID 8749752

• INTERMITTENT MICROMOTION AND POLYETHYLENE PARTICLES INHIBIT BONE INGROWTH INTO TITANIUM CHAMBERS IN RABBITS JOURNAL OF APPLIED BIOMATERIALS Goodman, S., Aspenberg, P., Song, Y., Regula, D., Lidgren, L. 1995; 6 (3): 161-165

  Abstract

  We performed a histomorphological and morphometric analysis of the effects of short daily periods of micromotion and phagocytosable particles of high density polyethylene (PE) on bone ingrowth into a 1 x 1 x 5 mm canal within a titanium chamber in rabbits. The micromotion chamber (MC) was implanted in the tibia of nine mature New Zealand white rabbits. After osseointegration and first harvest of tissue, 40 micromotions (amplitude = 0.5 mm) were applied daily at a rate of 1 Hz for a 3-week period. The tissue within the chamber was then harvested. For the second treatment, PE particles (10(8)/mL) were placed within the canal. The tissue in the chamber was harvested 3 weeks later. The next treatment was a 3-week rest period, in which neither micromotion nor particles were utilized; a harvest followed. The final treatment combined PE particles and micromotion, followed by a harvest 3 weeks later. Sections from control harvests contained extensive trabecular bone arranged longitudinally throughout the canal in a fibrovascular stroma. Micromotion produced longitudinally oriented fibrous tissue within the chamber. PE particles were associated with macrophages, surrounding and engulfing the birefringent particles. The combination of particles and micromotion produced a fibrous stroma laden with macrophages. PE particles and micromotion, alone or together, produced a similar effect in inhibiting bone ingrowth, compared to nonmoved chambers without particles. In this short-term experiment, no additive or potentiating effect of these two stimuli could be demonstrated.

  View details for PubMedID 7492805

• Tissue ingrowth and differentiation in the bone-harvest chamber in the presence of cobalt-chromium-alloy and high-density-polyethylene particles. journal of bone and joint surgery. American volume Goodman, S., Aspenberg, P., Song, Y., Knoblich, G., Huie, P., Regula, D., Lidgren, L. 1995; 77 (7): 1025-1035

  Abstract

  Particulate wear debris from joint replacements has been implicated in the etiology of periprosthetic bone resorption. However, the effect of high-density-polyethylene or cobalt-chromium-alloy particles on osteoclastic bone resorption in vivo has not been studied previously, to our knowledge. Therefore, we examined the effect of these particles on tissue ingrowth, net bone formation (per cent trabecular bone), and osteoclastic bone resorption (osteoclasts per unit of bone surface) with use of a bone-harvest chamber that had a transverse one-millimeter channel for tissue ingrowth. After an initial six-week period for incorporation of the chamber into the proximal part of the tibia of rabbits, the contents of the channel were harvested repeatedly at three-week intervals. The carrier solution, 1 per cent sodium hyaluronate, was implanted first. In subsequent implantations, the hyaluronate was mixed with high-density-polyethylene or cobalt-chromium particles at concentrations of 10(8) particles per milliliter. The tissue harvested from the chambers that contained no particles was composed of longitudinally oriented trabecular bone in a fibrovascular stroma. Particulate high-density polyethylene evoked a moderate foreign-body reaction and a chronic inflammatory response and decreased net bone formation. When cobalt-chromium particles had been implanted, the tissue exhibited a more florid foreign-body reaction and a chronic inflammatory response, often in a nodular arrangement, in a background of dense connective tissue. Bone was sparse, and areas of cell necrosis and hyaline degeneration were noted. Histomorphometric analyses were carried out to determine the amount of net bone formation and osteoclastic bone resorption in the presence or absence of high-density-polyethylene or cobalt-chromium particles. The amount of bone was greatest in the control specimens, moderately decreased in the presence of high-density-polyethylene particles, and greatly decreased in the presence of cobalt-chromium particles. The number of osteoclasts in Howship lacunae per unit of trabecular bone surface was increased in the presence of high-density polyethylene, indicating that these particles stimulate osteoclastic bone resorption.

  View details for PubMedID 7608224

• TISSUE INGROWTH AND DIFFERENTIATION IN THE BONE-HARVEST CHAMBER IN THE PRESENCE OF COBALT-CHROMIUM-ALLOY AND HIGH-DENSITY-POLYETHYLENE PARTICLES JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Goodman, S., Aspenberg, P., Song, Y., Knoblich, G., Huie, P., Regula, D., Lidgren, L. 1995; 77A (7): 1025-1035

  Abstract

  Particulate wear debris from joint replacements has been implicated in the etiology of periprosthetic bone resorption. However, the effect of high-density-polyethylene or cobalt-chromium-alloy particles on osteoclastic bone resorption in vivo has not been studied previously, to our knowledge. Therefore, we examined the effect of these particles on tissue ingrowth, net bone formation (per cent trabecular bone), and osteoclastic bone resorption (osteoclasts per unit of bone surface) with use of a bone-harvest chamber that had a transverse one-millimeter channel for tissue ingrowth. After an initial six-week period for incorporation of the chamber into the proximal part of the tibia of rabbits, the contents of the channel were harvested repeatedly at three-week intervals. The carrier solution, 1 per cent sodium hyaluronate, was implanted first. In subsequent implantations, the hyaluronate was mixed with high-density-polyethylene or cobalt-chromium particles at concentrations of 10(8) particles per milliliter. The tissue harvested from the chambers that contained no particles was composed of longitudinally oriented trabecular bone in a fibrovascular stroma. Particulate high-density polyethylene evoked a moderate foreign-body reaction and a chronic inflammatory response and decreased net bone formation. When cobalt-chromium particles had been implanted, the tissue exhibited a more florid foreign-body reaction and a chronic inflammatory response, often in a nodular arrangement, in a background of dense connective tissue. Bone was sparse, and areas of cell necrosis and hyaline degeneration were noted. Histomorphometric analyses were carried out to determine the amount of net bone formation and osteoclastic bone resorption in the presence or absence of high-density-polyethylene or cobalt-chromium particles. The amount of bone was greatest in the control specimens, moderately decreased in the presence of high-density-polyethylene particles, and greatly decreased in the presence of cobalt-chromium particles. The number of osteoclasts in Howship lacunae per unit of trabecular bone surface was increased in the presence of high-density polyethylene, indicating that these particles stimulate osteoclastic bone resorption.

  View details for Web of Science ID A1995RJ67100008

• UNTITLED JOURNAL OF ARTHROPLASTY GOODMAN, S. B. 1995; 10 (2): 255

  View details for DOI 10.1016/S0883-5403(05)80135-4

  View details for Web of Science ID A1995QV34200018

  View details for PubMedID 7798109

• UNTITLED JOURNAL OF ARTHROPLASTY SEDEL, L. 1995; 10 (2): 255

  View details for DOI 10.1016/S0883-5403(05)80136-6

  View details for Web of Science ID A1995QV34200019

  View details for PubMedID 7798110

• EFFECTS OF PARTICULATE HIGH-DENSITY POLYETHYLENE AND TITANIUM-ALLOY ON TISSUE INGROWTH INTO BONE HARVEST CHAMBER IN RABBITS JOURNAL OF APPLIED BIOMATERIALS Goodman, S., Aspenberg, P., Song, Y., Doshi, A., Regula, D., Lidgren, L. 1995; 6 (1): 27-33

  Abstract

  The purpose of this study was to determine whether small, phagocytosable particles of titanium alloy (Ti) and high-density polyethylene (HDPE) have an adverse effect on bone ingrowth. The bone harvest chamber (BHC) was implanted bilaterally in the proximal tibial metaphysis of six mature rabbits. The BHC has a transverse 1-mm wide pore providing a continuous canal through the chamber for tissue ingrowth. After an initial 6-week period for osseointegration of the BHC, the contents of the canal were harvested repeatedly at 3 weekly intervals. This could be done with the chamber in place, without disturbing its exterior surface or the surrounding bone. The carrier solution, 1% sodium hyaluronate (Healon) was implanted first. In subsequent implantations, Healon was mixed with particles of HDPE or Ti averaging 4.7 +/- 2.1 and 3.0 +/- 2.6 microns, respectively. The contralateral chamber was left empty and served as a control. The chambers were harvested repeatedly, alternating experimental and control sides. The sections from the control side, and those containing Healon alone demonstrated extensive trabecular bone in a fibrovascular stroma. The sections containing Ti alloy particles were qualitatively and quantitatively similar to the control sections and those containing Healon, except for the presence of small black granules of Ti alloy, dispersed in the fibrovascular stroma or phagocytosed by scattered macrophages. The sections containing HDPE particles were infiltrated and engulfed by mononuclear and multinuclear histiocytic cells in a highly fibrous stroma. The majority of the multinucleated cells present were interpreted as being foreign body giant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 7703535

• A clinical and radiographic study of the "safe area" using the direct lateral approach for total hip arthroplasty. journal of arthroplasty Comstock, C., Imrie, S., Goodman, S. B. 1994; 9 (5): 527-531

  Abstract

  The purpose of this clinical and radiographic study is to determine whether the surgeon can remain within the 5 cm "safe zone" while using the direct lateral approach during total hip arthroplasty (THA) without endangering the superior gluteal nerve. The direct lateral approach was used in a prospective, consecutive series of 36 primary THAs in 31 patients performed by one surgeon. At the time of closure of the abductor muscle layer, a small metallic clip was placed at the superior extent of the incision into the gluteus medius. After surgery, the patients were mobilized on crutches with protected weight bearing for either a 6-week (hybrid THA) or 12-week (uncemented THA) period. Before surgery, and at 3, 6, and 12 months after surgery, abductor strength and the Trendelenburg sign were measured by the same physical therapist. The vertical distance from the superior pole of the greater trochanter to the base of the clip was measured on all radiographs of the pelvis and corrected for magnification. Before surgery, only 25 of the 36 hips demonstrated abduction strength of 4/5 or greater. Three months after surgery, 34 hips had a grade of 4/5 or greater for abductor strength. The Trendelenburg sign was positive in 24 of 34 hips before surgery, in 5 hips at 3 months, in 1 hip at 6 months, but negative in all hips by 12 months. The clip was located 3.2 +/- 1.3 cm (mean +/- SD) vertically from the superior pole of the greater trochanter. In 34 of 36 hips (95%), the 5 cm safe zone was respected.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 7807111

• CESSATION OF STRAIN FACILITATES BONE-FORMATION IN THE MICROMOTION CHAMBER IMPLANTED IN THE RABBIT TIBIA BIOMATERIALS Goodman, S. B., Song, Y., Doshi, A., Aspenberg, P. 1994; 15 (11): 889-893

  Abstract

  Short, daily periods of externally-applied strain have been shown previously to affect the differentiation of mesenchymal tissue. In this study, we examine the effects of discontinuing a strain protocol known to produce primarily fibrous tissue rather than bone in the micromotion chamber (MC). Five MCs were inserted into the proximal tibial metaphysis of mature male New Zealand white rabbits. The MC has a 1 x 1 x 5 mm pore for tissue ingrowth. After osseointegration of the fixed outer cylinder of the chamber, the inner movable core was manipulated for 40 cycles per day delivered at a rate of 1 Hertz ('40'). This provided motion at the interface between the cylinder and the core. The tissue in the pore was harvested after 3 wks. The MCs were then manipulated at 40 cycles per day for 3 wks and then the manipulations were discontinued for 3 additional wks ('40 + 0'); the contents of the chamber were harvested after 6 wks. Finally, the chambers were left without manipulation ('0') and harvested after 3 wks. Histological sections from unmoved chambers ('0') contained extensive trabecular bone, embedded in a fibrovascular stroma. The '40' specimens were composed primarily of longitudinally orientated fibrous tissue. The '40 + 0' specimens were similar histologically to the '0' specimens. The amount of bone ingrowth expressed as a percentage of the area of the section averaged 37 +/- 6 (mean +/- standard error of the mean) for the '0' specimens, 20 +/- 2 for the '40' specimens and 37 +/- 7 for the '40 + 0' specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 7833435

• BONE FORMATION IN THE PRESENCE OF PHAGOCYTOSABLE HYDROXYAPATITE PARTICLES CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Wang, J. S., Goodman, S., Aspenberg, P. 1994: 272-279

  Abstract

  Small particles of biomaterials used in orthopaedic surgery have been shown to induce the resorption of bone. The purpose of this study was to determine whether phagocytosable particles of hydroxyapatite had an adverse effect on bone ingrowth. Bone harvest chambers were implanted bilaterally in the proximal tibial metaphyses of 13 mature rabbits. The bone harvest chamber has a transverse 1-mm wide pore, providing a continuous canal through the chamber for tissue ingrowth. After an initial 6-week period for osseointegration of the bone harvest chambers, the contents of the canal were harvested at 3-or 6-week intervals. Hydroxyapatite particles (diameter, 5 mu) were mixed with a carrier solution, 1% sodium hyaluronate, and implanted in the canal of one chamber in each animal. The contralateral chamber was implanted with the carrier only and served as a control. Histological sections from the tissue harvested from the chambers were evaluated by light microscopy and histomorphometry, and the area of bone ingrowth was measured as a percentage of total area in each section. At 3 weeks there was more bone in the hydroxyapatite sections than in controls; at 6 weeks there was no difference. Hydroxyapatite particles were incorporated within the matrix of new ingrown bone at both time periods. There was no evidence of granuloma formation or inflammation. Previous studies have shown that particles of high density polyethylene and bone cement adversely affect bone ingrowth in this model. The present results suggest that hydroxyapatite particles, small enough to be phagocytosed by macrophages, did not have such effects.

  View details for Web of Science ID A1994NX35200041

  View details for PubMedID 8020228

• EFFECTS OF INTERMITTENT MICROMOTION VERSUS POLYMER PARTICLES ON TISSUE INGROWTH - EXPERIMENT USING A MICROMOTION CHAMBER IMPLANTED IN RABBITS JOURNAL OF APPLIED BIOMATERIALS Goodman, S., Aspenberg, P., Song, Y., Regula, D., Doshi, A., Lidgren, L. 1994; 5 (2): 117-123

  View details for Web of Science ID A1994NL92200003

• THE EFFECTS OF MICROMOTION AND PARTICULATE MATERIALS ON TISSUE DIFFERENTIATION - BONE CHAMBER STUDIES IN RABBITS ACTA ORTHOPAEDICA SCANDINAVICA GOODMAN, S. B. 1994; 65: 1–43

  Abstract

  Motion at the interface between bone and implants for joint replacement may interfere with osseointegration and prosthesis stabilization. Particulate materials may cause foreign body and chronic inflammatory reactions resulting in bone resorption (osteolysis). The micromotion chamber (MC) and the bone harvest chamber (BHC) were implanted in the rabbit tibia, and the effects of micromotion and phagocytosable particulate materials on tissue formation within the chamber were assessed by studying bone ingrowth into a 1-mm pore. Using the MC, one short daily episode of motion (20 cycles/day, 0.5 mm amplitude) for three weeks decreased the amount of bone ingrowth. Using a different pore configuration, the same parameters of motion increased bone ingrowth. Increasing the amplitude of motion (from 0.5 to 0.75 mm), or the number of daily motion periods (from one to two per day) then decreased bone ingrowth. These studies suggest the existence of a window of externally applied strain: a small stimulus may facilitate and a large stimulus may discourage bone formation within the chamber. Cessation of a given set of motion parameters (producing primarily fibrous tissue) for an additional three weeks was accompanied by tissue differentiation into bone. Using the BHC, small, phagocytosable particles of bone cement, high density polyethylene and cobalt chrome alloy, at a concentration of 1.0 x 10(8) particles/mL, caused a foreign body reaction and inhibited the ingrowth of bone. Particles of titanium alloy had no effect on net bone formation. In studies using normal and immunodeficient rats, T lymphocytes were not a prerequisite for macrophages to phagocytose polyethylene particles. In the clinical situation, micromotion and particulate debris may be synergistic in producing prosthetic loosening. If an implant does not undergo osseointegration due to excessive micromotion, the fibrous tissue interface may provide a conduit for the subsequent migration of particles around the implant.

  View details for Web of Science ID A1994NZ64900001

  View details for PubMedID 8042498

• AN IN-VITRO STUDY OF FEMORAL INTRAMEDULLARY PRESSURES DURING HIP-REPLACEMENT USING MODERN CEMENT TECHNIQUE CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Song, Y., Goodman, S. B., Jaffe, R. A. 1994: 297-304

  Abstract

  Five femora (four cadaveric and one plastic) were used to measure the intramedullary pressures simultaneously at two different locations along the proximal femur during the insertion of bone cement and the femoral component using modern cement technique. The pressures were monitored by transducers located at the midpoint of each femoral stem (P1), and just beyond the tip of the femoral stem proximal to a cement plug (P2). Transient increases in intramedullary pressure were noted during the initial compaction of the bone cement using a conventional device. However, during insertion of the femoral component, the pressures at P1 and P2 increased dramatically to peak pressures exceeding 2385 mm Hg at P1 and 3710 mm Hg at P2 respectively. These pressure elevations were not sustained; eight to 10 minutes after prosthesis insertion, the pressures decreased to below baseline levels in all five femora. This probably resulted from contraction of the cement during the curing phase. Transient elevations of intramedullary pressure to levels greater than 100 times capillary pressure are produced during hip replacement using modern cement technique. The highest pressures are generated during insertion of the femoral component rather than during the cement compaction step. These findings suggest that the use of a cement compactor to improve intrusion of the cement into bone is probably unnecessary.

  View details for PubMedID 8168317

• SEGMENTAL WALL-MOTION ABNORMALITIES IN PATIENTS UNDERGOING TOTAL HIP-REPLACEMENT - CORRELATIONS WITH INTRAOPERATIVE EVENTS ANESTHESIA AND ANALGESIA PROPST, J. W., Siegel, L. C., Schnittger, I., FOPPIANO, L., Goodman, S. B., BROCKUTNE, J. G. 1993; 77 (4): 743-749

  Abstract

  We examined the effect of methylmethacrylate cement on venous embolization and cardiac function in 20 patients having total hip arthroplasty under general anesthesia. Segmental wall motion abnormalities and intracardiac targets (presumably emboli) were investigated by making videotaped recordings of the transgastric short axis and longitudinal 4-chamber views of the heart with transesophageal echocardiography at different points during surgery. The incidence of segmental wall motion abnormalities was the most frequent during insertion of cemented femoral prostheses (8 of 14 patients had wall motion abnormalities). This was significantly different from baseline measurements taken at the beginning of surgery (P < 0.05). In addition, there were also significantly more segmental wall motion abnormalities in patients having a cemented femoral component compared to those having an uncemented femoral prosthesis (P < 0.05). The incidence of wall motion abnormalities during acetabular and femoral reaming and during wound closure was not significantly different from baseline. Intracardiac targets (emboli) were seen in all 20 patients during surgery. The largest number of emboli occurred during reaming of the femur and during insertion of the femoral prosthesis. Significantly more emboli were seen with cemented components (P < 0.02). Most emboli were small (< 2 mm) and appeared similar to the microbubbles produced by agitating saline with a small amount of air. Six patients also had larger (> 5 mm) emboli that appeared to be solid material. One patent foramen ovale was detected (5% incidence). There were no adverse cardiac or neurologic events, and heart rate and arterial blood pressure remained within normal limits throughout surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 8214658

• Lysosomal enzyme production at the interface surrounding loose and well-fixed cemented tibial hemiarthroplasties in the rabbit knee. Journal of investigative surgery Goodman, S. B., Kang, T., Smith, R. L. 1993; 6 (5): 413-418

  Abstract

  Fourteen mature New Zealand white female rabbits had a right, cemented, tibial hemiarthroplasty using a stemmed, fluted, titanium alloy, condylar-type prosthesis. In one group (seven rabbits), polymethyl methacrylate (PMMA) was used to cement the prosthesis firmly. In a second group (seven rabbits), the prosthesis was treated with cement ex vivo; the prosthesis and cured cement were then implanted, and rotated once within the bone to ensure that the prosthesis was loose fitting. Roentgenograms performed postoperatively and at 3 months were graded for new (i.e., not present on the immediate postoperative radiograph) radiolucent lines. At 3 months, the tissue adjacent to the implant was harvested sterilely and cultured over a 3-day period; the tissues and culture supernatants were then assayed for total protein, DNA content, and lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase). The mean cumulative grading of new lucent lines was 0.4 +/- 0.3 (mean +/- standard error) for the well-fixed prosthetic group and 2.0 +/- 0.6 for the loose prosthetic group. The tissue surrounding loose prostheses contained more DNA and total protein, and produced greater amounts of lysosomal enzymes compared to well-fixed prostheses. The control left sides were not statistically different for any parameter analyzed. The increased DNA content demonstrates an increase in cellularity of the tissue surrounding loose prostheses. Normalization of the relative amount of enzyme released as a function of cellularity (DNA) suggests that the influx of cells into the area surrounding loose prostheses may be more important to the overall increase in lysosomal enzyme release than increased production of lysosomal enzymes by individual cells.

  View details for PubMedID 8292569

• HISTOLOGICAL REACTION TO TITANIUM-ALLOY AND HYDROXYAPATITE PARTICLES IN THE RABBIT TIBIA BIOMATERIALS Goodman, S. B., Davidson, J. A., Fornasier, V. L. 1993; 14 (10): 723-728

  Abstract

  The interfacial membrane harvested from failed joint replacements contains particulate debris from the materials used for the implant. To define the tissue response to particulate titanium alloy and hydroxyapatite (HA) alone, 16 mature New Zealand white rabbits were divided into 2 groups of 8 rabbits. Using sterile technique, a drill hole was placed anteromedially in the tibia, 1 cm distal to the knee joint bilaterally. The marrow was scooped out and 0.25 mg of either titanium alloy particles or HA particles were inserted in the right tibia. The titanium alloy particles had a diameter averaging 4.0 +/- 4.4 microns (mean +/- standard deviation) and an aspect ratio (the ratio of the maximum length divided by the maximum width) of 1.84. The HA particles had a diameter of 4.4 +/- 3.3 microns and an aspect ratio of 1.76. The left leg was prepared in a similar fashion, but no biomaterial was implanted. The animals were killed after 16 wk. The harvested tibiae were processed with decalcification and the plastic-embedded sections were subjected to histomorphological analysis. Black titanium alloy particles were present within the bone marrow fat between haematopoietic cells, and within scattered macrophages. The surrounding bone appeared to be unaffected. Within the spongiosa, the HA particles were surrounded by small numbers of mononuclear histiocytes or encased within a shell of new appositional bone. Where HA deposits were exposed to the endosteal aspect of bone, there was scalloping of the surface of the HA in a pattern suggestive of resorption or dissolution of the HA particles.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 8218720

• THE EFFECTS OF BONE-CEMENT POWDER ON HUMAN ADHERENT MONOCYTES MACROPHAGES IN-VITRO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Davis, R. G., Goodman, S. B., Smith, R. L., Lerman, J. A., Williams, R. J. 1993; 27 (8): 1039-1046

  Abstract

  This study reports the effects of Simplex bone cement powder (BC) on the proliferation and production of bone resorbing factors in vitro by human adherent monocytes/macrophages. Adherent peripheral blood cells were isolated from seven healthy individuals and exposed to a dispersion of BC powder (1 mg/mL), phytohemagglutinin (PHA, 40 micrograms/mL), or medium alone at different periods of cell incubation (days 0-2, 0-7, 5-7, or 10-12). Cell proliferation was quantified by incorporation of 3H-thymidine uptake. Culture supernatants were evaluated for levels of interleukin 1-like activity (IL-1) by murine thymocyte proliferation assay, prostaglandin E2 (PGE2) by radioimmunoassay, lysosomal enzyme activity (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase using fluorometry, and collagen and casein degrading activity using radioactive substrates. Human adherent peripheral blood cells showed a proliferative response to PHA that coincided with cell maturation; BC did not inhibit PHA-induced cell proliferation of either adherent or nonadherent blood cells, indicating the non-toxic nature of these particles at the concentrations tested. BC stimulated increased release of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase; the levels of PGE2, IL-1, collagenase, and caseinase were unchanged.

  View details for PubMedID 8408116

• EFFECTS OF MECHANICAL STIMULATION ON THE DIFFERENTIATION OF HARD TISSUES BIOMATERIALS Goodman, S., Aspenberg, P. 1993; 14 (8): 563-569

  Abstract

  In 1892, J.L. Wolff believed that bone was a dynamic organ that responded to the biomechanical environment. Research has shown that mechanical stimulation can have a profound effect on the differentiation and development of mesenchymal tissues. It would appear that a 'window' of mechanical strain exists which may facilitate or discourage the accretion of bone. With respect to processes such as fracture healing and ingrowth of bone into porous coated prostheses, it may be possible to modulate the mechanical environment with the application of well-defined, exogenous loads in order to promote a more favourable outcome.

  View details for PubMedID 8399946

• RADIOLOGICAL AND HISTOLOGICAL STUDY OF ASEPTIC LOOSENING USING A CEMENTED TIBIAL HEMIARTHROPLASTY IN THE RABBIT KNEE BIOMATERIALS Goodman, S. B., Magee, F. P., Fornasier, V. L. 1993; 14 (7): 522-528

  Abstract

  Fourteen mature New Zealand white female rabbits had a unilateral cemented, stemmed, titanium, condylar-type tibial hemiarthroplasty, using an anteromedial arthrotomy of the right knee. The articular cartilage and minimal bone were resected. There were two prosthetic groups of seven animals each: a well-fixed, non-loose group and a loose group. In the non-loose group, the implant was inserted into the cement bed and axially compressed until the PMMA had cured. In the loose group, the same volume of cement was allowed to cure on the implant ex vivo; the prosthesis was then implanted to ensure that it was loose fitting. Radiographs were performed at zero and 3 months and graded for new lucent lines. Histological analysis was performed using undecalcified coronal sections, surface stained with toluidine blue with the prosthesis in situ, and the cement mantle preserved. Back-scattered electron microscopy was also performed. The mean cumulative grading of new lucent lines was 0.3 +/- 0.1 for the non-loose group and 2.2 +/- 0.4 for the loose group (P < 0.005). Non-loose prostheses were surrounded by a thin fibrous membrane or bone. Loose prostheses were surrounded by a thicker, fibrous tissue layer, containing histiocytes and giant cells which were more prevalent around cement particles, especially near the prosthetic tip. These findings parallel the histology found at cemented prosthetic interfaces in humans. The results of this study suggest that the fibrohistiocytic membrane commonly found around loose cemented implants may be the result of, rather than the cause of, the loosening process.

  View details for PubMedID 8329525

• Bone accretion around polymethylmethacrylate and polyethylene implanted in the rabbit tibia. Contemporary orthopaedics Goodman, S. B., Fornasier, V. L., Lee, J. 1993; 26 (3): 292-297

  Abstract

  This study examines the accretion rate of bone surrounding orthopaedic polymeric implants in different physical forms. Forty mature, female, New Zealand white rabbits were used in the study. Bilateral 6mm drill holes were made in the anteromedial tibias, 1cm from the joint line. The right tibia received a polymeric implant and the left tibia functioned as a prepared but nonimplanted control. The animals were allocated as follows: Group 1--bulk, preformed cooled polymethylmethacrylate (PMMA) plug; Group 2--bulk, doughy PMMA implant; Group 3--cement polymer powder; Group 4--bulk ultra-high-molecular-weight polyethylene (UHMWP) plug; Group 5--UHMWP particles averaging 67.29 mum; Group 6--UHMWP particles averaging 15.68 mum. All animals received the same volume of PMMA or UHMWP. The animals were killed after four months by barbiturate overdose. Beginning four weeks prior to sacrifice, the animals were given tetracycline injections at two-weekly intervals for two consecutive days. The upper tibias were harvested bilaterally and the specimens were processed undecalcified. Using a fluorescent microscope, the distance between successive tetracycline bands was assessed. Doughy PMMA tended to suppress bone formation compared to the control side, whereas preformed PMMA plugs and particulate PMMA polymer did not. This may be due to the heat of polymerization or to the presence of residual monomer in the doughy group. Polyethylene tended to facilitate bone accretion whether in bulk or particulate form when compared to the control side or to doughy cement. This effect was less marked when the cement was in particulate form.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 10171629

• INCIDENCE OF SEGMENTAL WALL MOTION ABNORMALITIES DURING TOTAL HIP-REPLACEMENT PROPST, J., SIEGEL, L., SCHNITTGER, FOPPIANO, L., GOODMAN, S., BROCKUTNE, J. WILLIAMS & WILKINS. 1993: S338

  View details for Web of Science ID A1993KY03900336

• Late rupture of the posterior cruciate ligament after total knee replacement. The Iowa orthopaedic journal MONTGOMERY, R. L., Goodman, S. B., CSONGRADI, J. 1993; 13: 167-170

  Abstract

  To our knowledge there have been no reports of late rupture of the posterior cruciate ligament (PCL) as a cause of instability in PCL-retaining total knee prostheses. In our experience of 150 total knee replacements using PCL-retaining prosthesis, three cases (2.0%) of late rupture of the posterior cruciate ligament have occurred, each leading to chronic instability, disabling pain, and revision arthroplasty. In each case rupture of the posterior cruciate ligament was confirmed at the time of revision arthroplasty. The use of a more constrained prosthesis led to a successful outcome in each case.

  View details for PubMedID 7820738

• PROSTAGLANDIN-E2 PRODUCTION BY THE MEMBRANE SURROUNDING LOOSE AND FIXATED CEMENTED TIBIAL HEMIARTHROPLASTIES IN THE RABBIT KNEE CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., CHIN, R. C., Magee, F. P. 1992: 283-287

  Abstract

  Sixteen mature New Zealand female rabbits had cemented, tibial hemiarthroplasty of the right knee (correction of hip) using a stemmed, fluted, titanium-alloyed, condylar type prosthesis. In the fixated prosthetic group (eight rabbits), a 1.5-cm3 doughy bolus of polymethylmethacrylate (PMMA) was used to cement the prosthesis firmly. In the loose group (eight rabbits), the cement was allowed to cure ex vivo on the implant; the prosthesis was then implanted and rotated to ensure that it was loose fitting. Roentgenograms performed postoperatively and at three months were graded for new lucent lines. The implant area was harvested aseptically and cultured during a three-day period, and the cumulative collection of tissue culture supernatants was assayed for prostaglandin E2 (PGE2). The mean cumulative grading of new lucent lines was 0.4 +/- 0.2 (mean +/- SEM) for the fixated prosthetic group and 2.3 +/- 0.5 for the loose prosthetic group. Specimens from the nonloose group produced 8.85 +/- 1.44 ng of PGE2 on the right prosthetic side, and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted side. Specimens from the loose prosthesis group produced 52.35 +/- 16.28 ng of PGE2 on the right prosthetic side and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted side. Increased PGE2 production relative to fixated prostheses was noted in the membranes surrounding loose prostheses. The left, nonimplanted sides were not statistically different. Roentgenographic and biochemical evidence indicates that a cemented tibial hemiarthroplasty implanted in the rabbit knee can provide a short-term model of arthroplasty loosening.

  View details for PubMedID 1395306

• PROXIMAL FIBULAR STRESS-FRACTURE IN AN AEROBIC DANCER - A CASE-REPORT AMERICAN JOURNAL OF SPORTS MEDICINE Strudwick, W. J., Goodman, S. B. 1992; 20 (4): 481-482

  View details for PubMedID 1415897

• Preoperative templating for the equalization of leg lengths in total hip arthroplasty. Contemporary orthopaedics Goodman, S. B., HUENE, D. S., Imrie, S. 1992; 24 (6): 703-710

  Abstract

  The method and results of preoperative templating for the re-establishment of leg length equality during total hip replacement (THR) are reported. The method is a modification of the technique of Müller and requires an anteroposterior radiograph of the pelvis that includes the proximal third of both femora, appropriate acetabular and femoral templates, and tracing paper. To obtain equalization of leg lengths and tissue tension, a composite drawing is made of the operative plan, with all component sizes and important measurements clearly marked. During THR, the lesser trochanter is identified and the femoral neck is osteotomized after a direct measurement is made. These principles were followed in a prospective, consecutive series of 42 primary THR procedures performed by one surgeon. All the radiographic measurements were performed by a single observer. The leg length discrepancy on the postoperative radiograph averaged 3mm (standard deviation = 3mm, range: -9 to +9mm). The postoperative clinical leg length discrepancy averaged 0mm (range: -10 to +10mm). None of the patients complained of leg length inequality. Preoperative templating allows different alternatives to be traced on paper prior to the actual surgical procedure. This method also helps determine the requirements for special prosthetic implants. Acceptable results for postoperative leg length equality may be reliably achieved using this method.

  View details for PubMedID 10149945

• POLYETHYLENE WEAR IN KNEE ARTHROPLASTY - A REVIEW ACTA ORTHOPAEDICA SCANDINAVICA Goodman, S., Lidgren, L. 1992; 63 (3): 358-364

  View details for PubMedID 1609612

• COMPUTERIZED TOMOGRAPHIC EVALUATION OF ACETABULAR ANATOMY CLINICAL ORTHOPAEDICS AND RELATED RESEARCH OSULLIVAN, G. S., Goodman, S. B., Jones, H. H. 1992: 175-181

  Abstract

  In this study, accurate identification of the location of the acetabular teardrop and ilioischial line on the cadaveric pelvis was attempted using computerized tomographic (CT) scanning and conventional roentgenographic techniques. The acetabular teardrops and ilioischial lines of four whole pelvic anatomic specimens were outlined with barium impregnated latex strings utilizing conventional roentgenograms, fluoroscopy, and stereoscopic control. Computed tomographic scanning was then performed, and axial and coronal CT reformations were created. Roentgenograms, CT scans, and magnetic resonance images of the pelves of ten patients with avascular necrosis of the femoral head were also reviewed to correlate the cadaveric study with specific clinical cases. The acetabular teardrop is a U-shaped figure on roentgenograms taken in a neutral anteroposterior projection. It is a complex geometric structure found to be in a constant position in the anteroinferior aspect of the acetabular wall. Its appearance changes with rotation of the pelvis or incident beam, as the teardrop represents a two-dimensional image of the tangents of a series of curves of varying radii. The ilioischial line is located posterior to the acetabulum and corresponds to tangents on the cortex of the posterior column. Computed tomography imaging with reconstruction identifies acetabular anatomy most clearly and allows precise measurements to be made.

  View details for PubMedID 1555339

• INTERMITTENT MICROMOTION INHIBITS BONE INGROWTH - TITANIUM IMPLANTS IN RABBITS ACTA ORTHOPAEDICA SCANDINAVICA Aspenberg, P., Goodman, S., TOKSVIGLARSEN, S., Ryd, L., Albrektsson, T. 1992; 63 (2): 141-145

  Abstract

  We studied the effects of micromotion on bone ingrowth into a 1-mm canal through a titanium chamber implanted in the proximal tibia of rabbits. The implant surface became "osseointegrated," but an interior core was movable, allowing the central portion of the canal to be moved in relation to the ends. Thus, the ingrowing bone in the canal had to pass an area of ad latus motion. When implanted in rabbit tibiae, the canal became filled with ingrown cancellous bone. Bone ingrowth was inhibited by 20 cycles of 0.5-mm movement applied during a 30-second period once daily. With this regimen, the canal was usually filled with vascularized fibrous tissue and significantly less bone. The micromotion chamber may enable detailed studies of the effects of different motion variables on ingrowth of bone.

  View details for Web of Science ID A1992HU26800005

  View details for PubMedID 1590046

• A biomechanical study of two methods of internal fixation of unstable fractures of the femoral neck. A preliminary study. Journal of orthopaedic trauma Goodman, S. B., Davidson, J. A., Locke, L., Novotny, S., Jones, H., CSONGRADI, J. J. 1992; 6 (1): 66-72

  Abstract

  A model of an unstable femoral neck fracture was used in this study to compare the axial and torsional displacement obtained when the neck was fixed by a compression hip screw (CHS) and side plate, or three Knowles pins. Six paired, embalmed femora were mounted on a special, custom-made jig that grasped the femoral head and shaft securely. A standardized osteotomy was made with an oscillating saw, bisecting the distance between the lower cartilaginous portion of the femoral head and the intertrochanteric line. A 5-mm thick slice of bone was excised from the posteromedial quadrant of the distal fragment. The right or left femur in each pair was then randomly assigned to internal fixation with either three Knowles pins or a keyed CHS plus a 130 degrees four-hole side plate. After potting of the specimens and application of rosette strain gauges, axial displacements were measured during the application of in-plane and out-of-plane compressive loads. The resistance to torsion was also determined. There were no statistical differences between the two devices for compressive or torsional loading using this model.

  View details for PubMedID 1556626

• THROMBOEMBOLISM FOLLOWING MULTIPLE TRAUMA KNUDSON, M. M., COLLINS, J. A., GOODMAN, S. B., MCCRORY, D. W. WILLIAMS & WILKINS. 1992: 2–11

  Abstract

  The true incidence of thromboembolic complications following multiple trauma is unknown, and no method of prophylaxis has been shown to be both safe and effective in managing seriously injured patients. In this prospective study, 113 trauma patients were assigned on admission to receive either low-dose heparin (LDH), (5,000 U subcutaneously every 12 hours) or to wear sequential compression devices (SCDs) as prophylaxis against the development of deep venous thrombosis (DVT). Both groups of patients were serially studied with duplex venous ultrasound imaging to detect thrombus in the veins of the thigh. Ventilation-perfusion lung scans and pulmonary angiograms were performed when pulmonary embolism (PE) was suspected clinically. There were 12 patients who had thromboembolic complications, including 9 of 76 in the SCD group (12%) and 3 of 37 in the LDH group (8%). Five patients had DVT only, four had PE without detectable DVT, and three had both DVT and PE. None of the patients with PE died, and there were no major complications associated with either method of prophylaxis. Compared with the patients who did not develop DVT/PE, those with thromboembolic complications were older (49 +/- 23 vs. 36 +/- 17 years, p less than 0.02), spent more hospital days immobilized (24 +/- 15 vs. 10 +/- 13 days, p less than 0.001), received more transfusions (11 +/- 12 vs. 3 +/- 5 U, p less than 0.001) and had clotting abnormalities on admission, as demonstrated by prolonged PTT values (39 +/- 28 vs. 26 +/- 5 seconds, p less than 0.001). It appears that there is an identifiable subgroup of injured patients at highest risk for PE who warrant both prophylaxis and close surveillance for DVT.

  View details for DOI 10.1097/00005373-199201000-00002

  View details for Web of Science ID A1992HB85400002

  View details for PubMedID 1732568

• EFFECT OF AMPLITUDE OF MICROMOTION ON BONE INGROWTH INTO TITANIUM CHAMBERS IMPLANTED IN THE RABBIT TIBIA BIOMATERIALS Goodman, S., Aspenberg, P. 1992; 13 (13): 944-948

  Abstract

  The micromotion chamber for implantation in the rabbit tibia consists of two titanium components that have a 1 mm contiguous pore for bone ingrowth. The fixed, outer cylinder of the chamber contains a movable inner core that can be manually rotated. The model is unique because specific, discrete, daily periods of motion of a predetermined amplitude and frequency can be delivered to the ingrowing tissue. In the present study, we compared the histological and scintigraphic results of bone ingrowth into chambers having a congruently shaped interface that was moved 20 cycles/d with an amplitude of either 0.5 or 0.75 mm. Histological sections from both amplitude groups contained extensive new woven and trabecular bone, embedded in a fibrovascular network. However, the chambers with a larger amplitude of motion yielded less bone ingrowth than those with a smaller amplitude. These studies suggest that short, discrete periods of motion can stimulate the formation of fibrous tissue rather than bone using the parameters chosen in this model.

  View details for PubMedID 1477264

• FIXATION AND LOOSENING OF HIP PROSTHESES ACTA ORTHOPAEDICA SCANDINAVICA GOODMAN, S. B. 1991; 62 (6): 633

  View details for DOI 10.3109/17453679108994514

  View details for Web of Science ID A1991GW10800031

  View details for PubMedID 1767664

• SUPPRESSION OF PROSTAGLANDIN-E2 SYNTHESIS IN THE MEMBRANE SURROUNDING PARTICULATE POLYMETHYLMETHACRYLATE IN THE RABBIT TIBIA CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., CHIN, R. C., Chiou, S. S., Lee, J. S. 1991: 300-304

  Abstract

  Fifteen mature, New Zealand, female rabbits were divided into two groups. Using sterile technique, a 6-mm drill hole was made in the tibia 1 cm distal to the knee joint bilaterally. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer and the left leg functioned as a prepared, but nonimplanted, control. All animals were fed a standard diet. Whereas the six animals in Group 1 received regular water, the nine animals in Group 2 drank water in which sodium naproxen was dissolved (1.375 mg per ml). The animals were killed after 16 weeks. The implant area was harvested under sterile conditions and maintained in tissue culture. The cumulative collection of tissue culture supernatants over a three-day period was assayed for Prostaglandin E2 (PGE2) via radioimmunoassay. Specimens from Group 1 produced an average of 106.0 +/- 10.9 ng PGE2 on the right side, and 35.3 +/- 6.0 ng PGE2 on the left side. Specimens from Group 2 produced an average of 31.1 +/- 6.1 ng PGE2 on the right experimental side and 26.0 +/- 5.1 ng PGE2 on the left control side. The ratio of PGE2 values for the right divided by the left side yielded higher values in Group 1, compared to Group 2. Cement polymer particles have been shown to produce a florid foreign body histologic reaction similar to that associated with prosthetic loosening in man. This experiment has demonstrated that the increased PGE2 production by the membrane surrounding particulate cement polymer can be suppressed by the administration of an oral cyclo-oxygenase inhibitor. PGE2 has been previously shown to induce bone resorption in vivo and in vitro. The use of nonsteroidal antiinflammatory drugs may be indicated in retarding the bone loss associated with early prosthetic loosening.

  View details for PubMedID 1914312

• MODULATION OF THE MEMBRANE SURROUNDING PARTICULATE CEMENT AND POLYETHYLENE IN THE RABBIT TIBIA 1990 CONF ON BIOINTERACTIONS ( BIOINTERACTIONS 90 ) Goodman, S. B., Lee, J. S., CHIN, R. C., Chiou, S. S. ELSEVIER SCI LTD. 1991: 194–96

  Abstract

  Twenty-nine mature New Zealand white, female rabbits were divided into four groups. Using sterile technique, a 6 mm drill hole was made in the tibia 1 cm distal to the knee joint. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer (PMMA) (groups 1 and 2) or polyethylene particles (UHMWP) (groups 3 and 4). The left leg functioned as a prepared but non-implanted control. All animals were fed a standard diet; those in groups 1 and 3 received plain water, while groups 2 and 4 drank water in which sodium naproxen was dissolved (1.375 mg/ml). Animals were killed after 16 wk. The implant area was harvested and grown in tissue culture. The cumulative collection of tissue culture supernatants over 3 d was assayed for prostaglandin E2 (PGE2) via radioimmunoassay. PGE2 production was significantly higher in the membrane harvested from the right side containing particulate cement with no sodium naproxen (group 1) compared with controls (P less than 0.05). The ratio of PGE2 values for the right divided by the left side yielded higher values in group 1, compared with groups 2, 3 or 4 (P less than 0.01). Previous studies have suggested that particulate debris and PGE2 production are associated with arthroplasty loosening. This experiment has demonstrated that PGE2 production by the membrane surrounding particulate debris can be suppressed by the administration of oral sodium naproxen. Because non-steroidal anti-inflammatory drugs are known to inhibit prostaglandin synthesis in man, these agents may prove useful in retarding the bone loss associated with early prosthetic loosening.

  View details for PubMedID 1878453

• QUANTITATIVE COMPARISON OF THE HISTOLOGICAL EFFECTS OF PARTICULATE POLYMETHYLMETHACRYLATE VERSUS POLYETHYLENE IN THE RABBIT TIBIA ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY Goodman, S. B., Fornasier, V. L., Kei, J. 1991; 110 (3): 123-126

  Abstract

  Fourteen mature female New Zealand White rabbits underwent implantation of Simplex polymethylmethacrylate (PMMA) powder or particulate (average 67 microns) ultrahigh-molecular-weight polyethylene (UHMWPE) through a drill hole in the proximal right tibia. The left tibia functioned as a prepared but nonimplanted control. Animals were killed after 16 weeks. Histological examination of the bone-implant interface in the particulate PMMA group disclosed a florid foreign-body reaction with the presence of giant cells and histiocytes. The particulate UHMWPE group demonstrated positively birefringent UHMWPE fragments, rimmed by foreign-body giant cells and histiocytes, embedded in a loose connective tissue stroma. UHMWPE interfaces were thicker and contained more histiocytes and fibrocytes; PMMA interfaces contained more marrow cells and lymphocytes. This study underscores the importance of biomaterial debris in the process of aseptic loosening of cemented joint arthroplasties.

  View details for PubMedID 2059533

• Mechanical overload of a single compartment induces early degenerative changes in the rabbit knee: a preliminary study. Journal of investigative surgery Goodman, S. B., Lee, J., Smith, R. L., Csongradi, J. C., Fornasier, V. L. 1991; 4 (2): 161-170

  Abstract

  The purpose of this experiment was to determine whether mechanical overload of a single compartment of the knee in rabbits via proximal tibial osteotomy could produce early changes consistent with degenerative arthritis. Ten New Zealand white female rabbits were allocated into two groups. Group 1 (five animals) underwent a right 20 degrees valgus proximal tibial osteotomy to overload the lateral compartment of the knee. Group 2 (five animals) underwent a tibial osteotomy without malalignment (sham controls). The osteotomies were stabilized with a mini AO/ASIF plate and screws, allowing early mobilization. The left leg in each animal was left intact and served as a control. Animals were sacrificed after 3 months. Histological grading of the cartilage was performed according to Mankin et al. The mean histological gradings for the right minus the left knee were the same for the lateral and medial compartments in the 0 degrees sham osteotomy group. However, the mean histological grading of the "overloaded" lateral compartment was 2.4 times greater than the medial compartment in the 20 degrees valgus osteotomy group. These findings suggest that histological evidence of degenerative changes can be surgically induced in the rabbit knee by creating a biomechanical overload of one compartment.

  View details for PubMedID 2069926

• THE EFFECTS OF BULK VERSUS PARTICULATE TITANIUM AND COBALT CHROME ALLOY IMPLANTED INTO THE RABBIT TIBIA JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Goodman, S. B., Fornasier, V. L., Lee, J., Kei, J. 1990; 24 (11): 1539-1549

  Abstract

  Twenty-eight mature New Zealand white female rabbits were allocated into 4 groups of 7 rabbits. Group 1 received a coiled wire of cobalt chrome alloy (Vitallium) (16 gauge x 1 cm). Group 2 received an equal weight of cobalt chrome particles averaging 15.4 microns in diameter. Group 3 received a coiled wire implant of commercially pure (C.P.) titanium (16 gauge x 1 cm). Group 4 received the same weight of C.P. titanium particles averaging 3.8 microns. The implants were placed through a drill hole in the proximal right tibia; the left tibia served as a prepared but nonimplanted control. The animals were killed after 16 weeks and quantitative histology was performed on undecalcified sections of the implant area. Bulk cobalt chrome and titanium implants were surrounded by a thin, incomplete, fibrous tissue layer with decreased numbers of cells. Trabeculae of bone were present within this connective tissue envelope. Fingerlike projections of bone enveloped the implant where it abutted endosteal bone. Clumped and loosely scattered cobalt chrome and titanium particles were surrounded by a minimal amount of fibrous connective tissue. Smaller particles were present within cells. Hematopoietic cells abutted the bulk or particulate implants directly. There was no evidence of acute or chronic inflammation or foreign body reaction. These results should be contrasted with those of Howie et al. in which intraarticular cobalt chrome particles stimulated a rapid proliferation of macrophages and synovial degeneration after 1 week. This may be due to a direct toxic effect of metals in an intra-articular environment, the smaller particle size used in that study, or to abrasive injury to the hyaline cartilage and subsequent synovitis. Our results underscore the general inert properties of these metals in the short term, when implanted into bone in the sizes and physical forms chosen.

  View details for PubMedID 2279985

• PROSTAGLANDIN-E2 LEVELS IN THE MEMBRANE SURROUNDING BULK AND PARTICULATE POLYMETHYLMETHACRYLATE IN THE RABBIT TIBIA - A PRELIMINARY-STUDY CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., CHIN, R. C. 1990: 305-309

  Abstract

  Fourteen mature New Zealand white female rabbits were allocated into two groups. Group 1 received a bolus doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group 2 received an equal volume of particulate PMMA cement powder. The operated but nonimplanted left tibiae served as controls. The animals were killed after four months. The membrane surrounding the implant area was harvested aseptically and grown in tissue culture. The supernatants were assayed for prostaglandin E2 (PGE2) via radioimmunoassay. Bulk cement specimens produced on average 12.39 +/- 4.11 ng PGE2 on the right experimental side and 12.29 +/- 3.56 ng PGE2 on the left control side (not statistically different). Cement powder specimens produced 8.82 +/- 1.64 ng PGE2 on the right experimental side, which was statistically different from 4.21 +/- 0.88 ng PGE2 produced on the left control side. The ratio of PGE2 values for the right divided by the left side and the arithmetic difference between right and left sides were significantly higher in the particle group compared with the bulk group. Small, undigestable cement particles may be phagocytosed by foreign-body giant cells and histiocytes and then extruded into the extracellular compartment, along with substances such as PGE2. PGE2 has been implicated as the biologic mechanism for stimulating the bone lysis associated with prosthetic loosening.

  View details for PubMedID 2199124

• Comparison of radiographic parameters for analysis of normal and dysplastic hips in the adult. Contemporary orthopaedics Goodman, S. B. 1990; 20 (5): 505-511

  Abstract

  Radiographic quantitation of the dysplastic hip in adults is difficult. This study compares the values for commonly used indices, the acetabular angle (AA), the center edge angle (CEA), and femoral head coverage, and the X-Y coordinate system on the anteroposterior pelvic radiograph in 30 adult patients with 60 normal hips, and 20 adult patients with 27 dysplastic hips. Dysplastic hips demonstrated significantly higher values for the AA and the X-Y coordinates, and significantly lower values for the CEA and femoral head coverage compared to normal hips. Femoral head coverage in dysplastic hips correlated best (negatively) with the Y coordinate, i.e., poorer coverage was associated with greater superior migration of the femoral head. The AA describes the slope of the acetabular roof, but does not take into account the relative position of the femoral head. The CEA measures the position of the femoral head in relation to the lateral lip of the acetabulum, but does not necessarily use the true acetabulum. The X-Y coordinate system relates the center of the femoral head to an identifiable acetabular landmark, the teardrop shadow. These coordinates are easily determined and can serve as an adjunct to other radiographic indices that quantitate the amount of subluxation in dysplastic hips in adults.

  View details for PubMedID 10148037

• THE HISTOLOGICAL EFFECTS OF THE IMPLANTATION OF DIFFERENT SIZES OF POLYETHYLENE PARTICLES IN THE RABBIT TIBIA JOURNAL OF BIOMEDICAL MATERIALS RESEARCH Goodman, S. B., Fornasier, V. L., Lee, J., Kei, J. 1990; 24 (4): 517-524

  Abstract

  This study examines the histological effects of different sizes of polyethylene particles implanted into the rabbit tibia. Seventeen mature New Zealand white female rabbits were allocated into three groups. Group 1 (5 rabbits) received polyethylene particles averaging approximately 16 microns in diameter, implanted into the right proximal tibia through a drill hole. Group 2 (5 animals) received particles averaging 26 microns, and Group 3 (7 rabbits) received particles averaging 67 microns. The left tibia was drilled but not implanted. Animals were sacrificed after 16 weeks. Histological analysis disclosed decreased hematopoietic activity within the left tibial drill hole. In all groups, the right tibia demonstrated positively birefringent polyethylene particles surrounded by, and within (smaller particles), histiocytes and giant cells in a fibrous tissue stroma. Statistical analysis disclosed more fibrocytes and less marrow cells at the interface of Group 3 (largest particles) compared to Group 1 and 2. Larger polyethylene particles, being less readily phagocytosed, appear to produce more fibrous encapsulation, compared to particles of a smaller size. The histological reaction stimulated by the different sizes of polyethylene particles resembled the membrane surrounding loose joint arthroplasties in humans.

  View details for PubMedID 2189880

• BENIGN VERSUS PATHOLOGICAL COMPRESSION FRACTURES OF VERTEBRAL BODIES - ASSESSMENT WITH CONVENTIONAL SPIN-ECHO, CHEMICAL-SHIFT, AND STIR MR IMAGING RADIOLOGY Baker, L. L., Goodman, S. B., Perkash, I., Lane, B., Enzmann, D. R. 1990; 174 (2): 495-502

  Abstract

  Differentiation of benign from pathologic compression fractures of vertebral bodies was evaluated with magnetic resonance imaging in a prospective study of 53 patients. Twenty-six patients had 34 benign posttraumatic compression fractures. Twenty-seven patients had metastatic disease to the vertebral column and seven pathologic fractures. T1- and T2-weighted spin-echo (SE) sequences (1.5 T) were performed in all patients. A presaturation technique was used to obtain "fat" and "water" images to better assess the degree of normal fatty marrow replacement in fractured vertebrae. Short inversion-time inversion-recovery (STIR) images were also obtained. Discrimination between benign and pathologic compression fractures was generally possible with the SE sequences. Chronic benign fractures demonstrated isointense marrow signal intensity (SI), compared with that of normal vertebrae with all sequences. Pathologic fractures showed low SI on T1-weighted images and high SI on T2-weighted images. Fat images revealed complete replacement of normal fatty marrow, shown as absent SI in the involved vertebral body. Water and STIR images showed diffuse high SI in pathologic fractures, with STIR images having the highest contrast between abnormal and normal marrow. Acute benign compression fractures also demonstrated high SI on T2-weighted, water, and STIR images, but the SI was less pronounced and the pattern was generally more inhomogeneous than that of pathologic compressions. In general, fat images showed only partial replacement of normal fatty marrow by low SI, in contrast to the complete absence of marrow SI typical of pathologic fractures.

  View details for PubMedID 2296658

• Compartment syndrome after intramedullary nailing of the tibia. journal of bone and joint surgery. American volume TISCHENKO, G. J., Goodman, S. B. 1990; 72 (1): 41-44

  Abstract

  Three patients had compartment syndrome of the leg after tibial intramedullary nailing with reaming. They were all treated successfully with emergency fasciotomy. A prospective study was done of seven additional patients who had continual monitoring of the pressure in the deep posterior compartment during tibial intramedullary nailing with reaming. In five of them, the procedure was performed three weeks or less after injury and in the remaining two, the nailing was performed later for the treatment of non-union. Two pressure peaks in the deep posterior compartment were noted: one after strong longitudinal traction was applied and the fracture was reduced and the other during intramedullary reaming. Intraoperative pressure of thirty millimeters of mercury or more were recorded in three of the seven patients. In the treatment of tibial fractures, operative procedures that involve forceful traction for a long time may predispose the patient to compartment syndrome in the leg. Close clinical observation of such patients is needed. When there is a high risk of compartment syndrome, monitoring of the pressure in the compartment may be prudent.

  View details for PubMedID 2295671

• COMPARTMENT SYNDROME AFTER INTRAMEDULLARY NAILING OF THE TIBIA JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME TISCHENKO, G. J., Goodman, S. B. 1990; 72A (1): 41-44

  Abstract

  Three patients had compartment syndrome of the leg after tibial intramedullary nailing with reaming. They were all treated successfully with emergency fasciotomy. A prospective study was done of seven additional patients who had continual monitoring of the pressure in the deep posterior compartment during tibial intramedullary nailing with reaming. In five of them, the procedure was performed three weeks or less after injury and in the remaining two, the nailing was performed later for the treatment of non-union. Two pressure peaks in the deep posterior compartment were noted: one after strong longitudinal traction was applied and the fracture was reduced and the other during intramedullary reaming. Intraoperative pressure of thirty millimeters of mercury or more were recorded in three of the seven patients. In the treatment of tibial fractures, operative procedures that involve forceful traction for a long time may predispose the patient to compartment syndrome in the leg. Close clinical observation of such patients is needed. When there is a high risk of compartment syndrome, monitoring of the pressure in the compartment may be prudent.

  View details for Web of Science ID A1990CL60500007

• The histology of a failed shelf procedure. Orthopaedic review SMITH, J. T., Goodman, S. B., Fornasier, V. L. 1989; 18 (10): 1069-1072

  Abstract

  Clinical, radiographic and histologic findings are reported in a patient who underwent a hip shelf procedure 24 years previously. While the histologic observations confirm the presence of metaplasia of the surgically formed articular surface to fibrocartilage, there are superadded degenerative changes morphologically similar to those seen in degenerative arthritis.

  View details for PubMedID 2608303

• Postoperative blood salvage using the Cell Saver after total joint arthroplasty. journal of bone and joint surgery. American volume SEMKIW, L. B., Schurman, D. J., Goodman, S. B., Woolson, S. T. 1989; 71 (6): 823-827

  Abstract

  The purpose of this study was to investigate whether the salvage in the recovery room of blood from the drainage tubes of patients who had total joint arthroplasty was both feasible and efficacious. The cases of seventy-four patients who had seventy-six consecutive total hip or knee arthroplasties were studied prospectively. Intraoperative salvage of blood was performed using the Cell Saver. After closure of the fascial layer or joint capsule, the drainage tubes were connected to the Cell Saver in the operating room and remained connected in the recovery room for a mean of 2.9 hours. Blood that was collected in the recovery room was then processed and transfused back to the patient. The average amount of blood that was salvaged after different types of arthroplasty varied. The addition of bone cement to the acetabular side during primary total hip replacement decreased the amount of postoperative bleeding and of salvaged blood (p = 0.018), whereas cementing the femoral component had no statistically significant effect. Revision total hip replacement also resulted in more bleeding and in the collection of more blood in the recovery room than did primary total hip replacement (p = 0.03), especially if cement was not used (p less than 0.001). There were no statistical differences in the amount of blood that was collected in the recovery room after unilateral, bilateral, primary, or revision total knee replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 2745477

• POSTOPERATIVE BLOOD SALVAGE USING THE CELL SAVER AFTER TOTAL JOINT ARTHROPLASTY JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME SEMKIW, L. B., Schurman, D. J., Goodman, S. B., Woolson, S. T. 1989; 71A (6): 823-827

  Abstract

  The purpose of this study was to investigate whether the salvage in the recovery room of blood from the drainage tubes of patients who had total joint arthroplasty was both feasible and efficacious. The cases of seventy-four patients who had seventy-six consecutive total hip or knee arthroplasties were studied prospectively. Intraoperative salvage of blood was performed using the Cell Saver. After closure of the fascial layer or joint capsule, the drainage tubes were connected to the Cell Saver in the operating room and remained connected in the recovery room for a mean of 2.9 hours. Blood that was collected in the recovery room was then processed and transfused back to the patient. The average amount of blood that was salvaged after different types of arthroplasty varied. The addition of bone cement to the acetabular side during primary total hip replacement decreased the amount of postoperative bleeding and of salvaged blood (p = 0.018), whereas cementing the femoral component had no statistically significant effect. Revision total hip replacement also resulted in more bleeding and in the collection of more blood in the recovery room than did primary total hip replacement (p = 0.03), especially if cement was not used (p less than 0.001). There were no statistical differences in the amount of blood that was collected in the recovery room after unilateral, bilateral, primary, or revision total knee replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1989AG26400004

• A CLINICAL PATHOLOGIC BIOCHEMICAL-STUDY OF THE MEMBRANE SURROUNDING LOOSENED AND NONLOOSENED TOTAL HIP ARTHROPLASTIES CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., CHIN, R. C., Chiou, S. S., Schurman, D. J., Woolson, S. T., MASADA, M. P. 1989: 182-187

  Abstract

  The clinical and roentgenologic data from 31 excised components from 19 revision arthroplasty cases were correlated with the histology and biochemistry of the membrane at the bone-cement or bone-prosthesis interface. Twenty-seven components were cemented and four were uncemented. Twenty-four implants were clinically and roentgenologically loose, one was possibly loose, and six were well fixed. Loose components, whether cemented or not, demonstrated statistically higher prostaglandin E2 levels in the surrounding membrane compared to the nonloose group. Collagenase and M-collagenase levels were absent or insignificantly low in all specimens; no detectable interleukin 1 beta was found. This suggests that prostaglandin E2 may be associated with the bone lysis associated with prosthesis loosening.

  View details for PubMedID 2545398

• SUPRACONDYLAR FRACTURE OF THE FEMUR AFTER GUEPAR TOTAL KNEE ARTHROPLASTY - A NEW TREATMENT METHOD CLINICAL ORTHOPAEDICS AND RELATED RESEARCH ROSCOE, M. W., Goodman, S. B., Schatzker, J. 1989: 221-223

  Abstract

  A 71-year-old woman incurred an unstable, comminuted supracondylar fracture of the femur above the tip of a GUEPAR prosthesis. The prosthesis was not loose. Immediate open reduction and internal fixation were performed using a segment cut from an intramedullary rod. This provided axial alignment and functioned as an internal stent with stable fixation of the fracture. Supplementary fixation with a plate and screws, cerclage wires, and an autogenous bone graft led to early mobilization, solid bony union, and an excellent functional result.

  View details for Web of Science ID A1989T934300027

  View details for PubMedID 2924468

• FEMORAL-NECK ARTHROPLASTY AFTER FAILED RESURFACING - BRIEF REPORT JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME SHERMAN, R. M., GOODMAN, S. B., SCHATZKER, J. 1989; 71 (2): 330–31

  View details for Web of Science ID A1989T848700046

  View details for PubMedID 2925764

• THE ACETABULAR TEARDROP AND ITS RELEVANCE TO ACETABULAR MIGRATION CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Adler, S. J., Fyhrie, D. P., Schurman, D. J. 1988: 199-204

  Abstract

  Five pelvises were photographed, roentgenographed, and sequentially sectioned or reamed to determine the location and appearance of the acetabular teardrop figure. The teardrop is located inferomedially in the acetabulum, just superior to the obturator foramen. The lateral lip is the exterior, and the medial lip is the interior of the acetabular wall. The ilioischial line projects over the medial acetabulum only fortuitously on the straight anteroposterior (AP) roentgenogram. Because of parallax, the relationship between the ilioischial line and the teardrop changes for views varying as little as 10 degrees in horizontal obliquity from the true AP roentgenogram. Because the teardrop comprises a well-defined, constant portion of the medial acetabular wall whereas the ilioischial line does not, the authors recommend using the acetabular teardrop rather than the ilioischial line for the detection and measurement of medial and superior acetabular migration.

  View details for PubMedID 3180571

• THE EFFECTS OF BULK VERSUS PARTICULATE POLYMETHYLMETHACRYLATE ON BONE CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Fornasier, V. L., Kei, J. 1988: 255-262

  Abstract

  Twenty-one mature New Zealand white female rabbits were allocated into three groups of seven rabbits. Group I received a bolus of doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group II received a preformed, cooled, bulk PMMA pellet. Group III had particulate PMMA powder implanted. The operated, but nonimplanted, left tibiae served as controls. Animals were killed after four months. Histologically, both Group I and Group II demonstrated a thin, fibrous tissue membrane at the implant interface. Particulate PMMA (Group III) stimulated a much thicker, florid, foreign body reaction composed of histiocytes and giant cells. The foreign body response to particulate acrylic cement was similar to that seen in failed cemented joint replacement arthroplasty in humans.

  View details for PubMedID 3289814

• PROSTHETIC HIP INFECTION CAUSED BY LISTERIA-MONOCYTOGENES JOURNAL OF INFECTIOUS DISEASES ARATHOON, E., GOODMAN, S. B., VOSTI, K. L. 1988; 157 (6): 1282–83

  View details for DOI 10.1093/infdis/157.6.1282

  View details for Web of Science ID A1988N738500036

  View details for PubMedID 3373031

• The effects of bulk versus particulate ultra-high-molecular-weight polyethylene on bone. journal of arthroplasty Goodman, S. B., Fornasier, V. L., Kei, J. 1988; 3: S41-6

  Abstract

  Fourteen mature New Zealand white female rabbits underwent implantation of a bulk pellet and of particulate (less than 1,000 micron) ultra-high-molecular-weight polyethylene (UHMWPE), through a drill hole in the proximal right tibia. The left tibia served as a drilled but nonimplanted control. The rabbits were killed after 16 weeks. Histologic examination of the bone-implant interface in the bulk UHMWPE group disclosed a fibrous tissue membrane with infrequent giant cell and histiocytic clusters at surface irregularities. The particulate group demonstrated positively birefringent UHMWPE fragments, rimmed by foreign body giant cells and histiocytes, embedded in a loose connective tissue. The histologic response to particulate UHMWPE is similar to that seen surrounding loose total joint arthroplasties in humans.

  View details for PubMedID 3058870

• Outcome of infected total hip arthroplasty. An inclusive, consecutive series. journal of arthroplasty Goodman, S. B., Schurman, D. J. 1988; 3 (2): 97-102

  Abstract

  Twenty-one infected total hip arthroplasties in 19 patients performed between 1971 and 1982 were prospectively followed, using a computerized standard orthopaedic arthritis record. These cases represent an inclusive and unselected, consecutive series. The mean follow-up period from time of infection was 4.8 years (range, 1.2-11.7 years). Infection was diagnosed by positive bacteriologic culture. Ten hips grew a staphylococcal species, 5 a single gram-negative organism, 1 a Streptococcus, and 5 multiple organisms. At final follow-up evaluation, only three hips (14%) had the previously infected prosthesis still in situ, and these had no evidence of ongoing deep infection. Five additional hips (24%) were successfully salvaged after one- or two-stage prosthetic exchange. Two hips (10%) have an infected prosthesis in situ. Eleven hips (52%) had resection arthroplasty, three after attempts at prosthetic reinsertion. Therefore, at final follow-up evaluation, only 8 of the 21 hips (38%) have an apparently infection-free salvaged or reinserted prosthesis in place. Good prognostic factors for prosthetic salvage/successful reinsertion include Staphylococcus epidermidis infection and a traumatic etiology necessitating later hip arthroplasty. Poor prognostic factors include infection with Staphylococcus aureus or multiple organisms and a preoperative diagnosis of avascular necrosis.

  View details for PubMedID 3397752

• A METHOD OF PROTECTIVE BANDAGING FOR POSTSURGICAL RABBITS BAUMGARDNER, W. L., BLUM, MONTANA, S. L., GOODMAN, S. B., HAMM, T. E. AMER ASSOC LABORATORY ANIMAL SCIENCE. 1987: 538

  View details for Web of Science ID A1987J895200131

• INTERMEDIATE RESULTS OF A STRAIGHT STEM PROSTHESIS IN PRIMARY TOTAL HIP-ARTHROPLASTY CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Goodman, S. B., Schatzker, J. 1987: 111-122

  Abstract

  In a retrospective study of 130 primary total hip arthroplasties with a self-locking straight stem femoral component (Muller) and low profile cup, the average follow-up evaluation was 3.1 years (range, 2.0-4.6 years). According to the clinical rating system modified from Swanson and Evarts, there were 115 (88.3%) excellent, six (4.7%) good, four (3.1%) fair, and five (3.9%) poor results. Radiolucent lines at least 1 mm in width were noted in 12.8% of acetabula, mostly in Zones 1 and III. One cup has been revised and one is awaiting revision. Radiolucent lines greater than or equal to 1 mm were noted around 26.5% of femoral components. These were asymptomatic, unless associated with the presence of infection, subsidence greater than 5 mm, or symptoms of acetabular loosening. True femoral subsidence was pain free and nonprogressive in seven patients (6%) if less than or equal to 5 mm. Femoral loosening was roentgenographically observed as component migration or subsidence greater than 5 mm. By these criteria, three femoral components (2.6%) were loose, although none have been revised.

  View details for Web of Science ID A1987H166300017

  View details for PubMedID 3568471

• HIP MOTION CHANGES IN HEMOPHILIA JOURNAL OF PEDIATRIC ORTHOPAEDICS Goodman, S., Gamble, J. G., Dilley, M. 1987; 7 (6): 664-666

  Abstract

  We reviewed early and late motion changes of the hip in 102 hemophiliacs with a mean follow-up of 7 years. Sixty patients (59%) had at least one hip bleed. Sixty-four hips in 49 patients demonstrated at least a 15 degree change in range of motion (ROM) at some time. At final review, only 34 of these 64 hips (53%) lost motion. Patients whose hips lost motion were just as likely to report hip bleeds as those who lost no motion. Twenty hips examined within 2 months of bleeding lost significant motion, but most motion returned within a year. The relationship between hip girdle bleeding and ROM remains obscure.

  View details for PubMedID 3429650

• Revision hip surgery using the straight-stem Muller prosthesis. journal of arthroplasty Goodman, S. B., Schatzker, J. 1987; 2 (2): 83-88

  Abstract

  Thirty-two cemented revision hip arthroplasties done with a straight-stem Muller prosthesis were reviewed an average of 3 years after operation (range, 2-4.4 years). Acetabular revision, performed in 29 cases, we done with a support ring, mesh, or bone graft in 18 of 29 (62%) cases. Acetabular and femoral cement pressurization techniques were not used. Trochanteric osteotomy was done in 15 cases (47%). The average patient age was 60.2 years (range, 20-85 years). Based on the clinical rating system of Swanson and Evarts, there were 21 (65.6%) excellent, 2 (6.3%) good, 8 (25%) fair, and 1 (3.1%) poor results. The clinical outcome was better after revision from a resurfacing arthroplasty (87.5% good/excellent results) than from uni/bipolar or total hip arthroplasty (60%). Radiographic examination suggests that two femoral components and one acetabular component are loose. These patients have a fair clinical rating. None have been revised. Trochanteric wire breakage (60%) and displacement (26.7%) was common if trochanteric osteotomy was done.

  View details for PubMedID 3612143

• Acetabular lucent lines and mechanical stress in total hip arthroplasty. journal of arthroplasty Goodman, S. B., Carter, D. R. 1987; 2 (3): 219-224

  Abstract

  The radiographs of 97 patients (117 hips) who had a straight-stem Muller femoral component and a non-metal-backed acetabular component were reviewed to determine whether the mode of acetabular loosening predicted by finite element stress analysis (FESA) is observed clinically. The follow-up period averaged 3.1 years (range, 2.0-4.6 years). Significantly more lucent lines were present in zones 1 and 3, compared with zone 2 (P less than .01). This finding corroborates the predictions of FESA and suggests that the production of acetabular lucent lines is due in part to chronic mechanical overload.

  View details for PubMedID 3668551

• INTERNAL-FIXATION OF FEMORAL-NECK FRACTURES - A PROSPECTIVE-STUDY CANADIAN JOURNAL OF SURGERY Goodman, S. B., Schatzker, J. 1986; 29 (5): 351-356

  Abstract

  To determine the adequacy of reduction and the soundness of the technique of primary internal fixation, the authors studied prospectively 96 femoral neck fractures over 6 1/2 years. Patients were followed up for an average of 11 months. The mean patient age was 70 years. Both clinical and radiologic data were collected at 3-month intervals for 6 months and then annually. Radiologic indices recorded included the Garden classification and index, shear angle, Western Infirmary Glasgow angle, lateral angle, nail placement, occurrence of bony union and presence of avascular necrosis. The fixation devices included sliding compression screw and side plate, multiple Knowles pins and a 130 degrees AO blade plate. A high rate of varus reduction, excessive ante- or retroversion and poor nail placement were all noted. Twenty-three patients required a total of 36 reoperations. There were six deaths in the first 6 months after operation. Eighty-five patients (mean age 79 years) with femoral neck fractures treated by hemiarthroplasty (71) or total hip replacement (14) during the same period were also reviewed. Follow-up averaged 8 months. Two patients required reoperation. The general morbidity was similar to that of the group treated by internal fixation, but there were eight deaths. Femoral neck fractures, if treated by internal fixation, demand accurate reduction and fixation for optimum results. Primary prosthetic replacement should be reserved for elderly patients with poor bone stock.

  View details for Web of Science ID A1986E143100021

  View details for PubMedID 3756658

• FRACTURE OF A POLYETHYLENE ACETABULAR CUP - A CASE-REPORT CANADIAN JOURNAL OF SURGERY Heller, M., Schatzker, J., Goodman, S. B. 1986; 29 (1): 48-49

  Abstract

  Fracture of a polyethylene acetabular cup is rare. Current theories of its cause emphasize wear of the component. The case reported illustrates the presence of a loosening membrane in association with cup fracture. Histologic study of the loosening membrane indicated a foreign-body reaction to polyethylene and acrylic wear particles. The authors propose a theory relating micromotion of the acetabular component to the production of particles of wear with a subsequent foreign-body reaction followed by further loosening. The erosion of bony support leads to the concentration of stress at the junction of the supported and unsupported segments. This may ultimately result in fracture of the cup.

  View details for Web of Science ID A1986AXZ2900021

  View details for PubMedID 3510067

• A study of implant failure in the Wagner resurfacing arthroplasty. journal of bone and joint surgery. American volume Bell, R. S., Schatzker, J., Fornasier, V. L., Goodman, S. B. 1985; 67 (8): 1165-1175

  Abstract

  Using clinical, radiographic, and pathological data, we investigated eighteen cases of early aseptic failure of an implant in patients who had undergone reconstruction of the hip with a Wagner resurfacing prosthesis. Sixteen patients required revision for loosening of the acetabular component, with eight of them also demonstrating loosening of the femoral component. One patient had loosening of the femoral component without failure of the acetabular component, and one patient sustained a femoral neck fracture that was associated with osteonecrosis. Six of the patients with loosening of the acetabular component had an associated significant loss of acetabular bone stock. Loosening was associated with the development of a membrane at the bone-cement interface in all patients. Histological examination of the membrane demonstrated a marked foreign-body response to wear products from the arthroplasty. Bone resorption appeared active at the bone-membrane interface. We concluded that the acetabular component of the Wagner prosthesis is prone to early loosening and that the early loosening is potentiated by a foreign-body response to debris resulting from arthroplastic wear.

  View details for PubMedID 3902844

• THE EFFECT OF POLYMETHYLMETHACRYLATE ON BONE - AN EXPERIMENTAL-STUDY ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY Goodman, S. B., Schatzker, J., SUMNERSMITH, G., Fornasier, V. L., GOFTEN, N., Hunt, C. 1985; 104 (3): 150-154

  Abstract

  In order to assess the response of bone to low-viscosity polymethylmethacrylate, CMW or Simplex acrylic cement was digitally packed while in a doughy state into drill holes in the proximal diaphysis in each of four long bones (humeri and tibiae) of mongrel dogs. Histological assessment was performed in areas of minimal load at the interface between the viscoelastic bone and the acrylic cement. Decalcified and undecalcified sections were evaluated and a remodeling or activity index calculated. Fluorescent labeling studies were performed in order to assess bone growth. Animals were killed at 2, 4 or 5 months. Histological analysis showed a thin connective-tissue membrane containing scattered giant cells and histiocytes at the bone-cement interface. Inflammation was not an important facet of this response. The marrow and trabecular bone were viable, except for scattered localized areas of marrow necrosis and fibrosis immediately adjacent to the cement. The bone adjacent to the cement showed a lower remodeling or activity index, fewer fluorescent bands, and smaller distances between successive bands, suggesting decreased bone formation and turnover. The etiology of these findings may include a vascular disturbance secondary to disruption of the cortical and marrow circulation, temperature effects during cement polymerization, and/or chemical effects from the acrylic monomer.

  View details for Web of Science ID A1985ARH3200003

  View details for PubMedID 3904668

• OLLIERS DISEASE WITH MULTIPLE SARCOMATOUS TRANSFORMATIONS HUMAN PATHOLOGY Goodman, S. B., Bell, R. S., Fornasier, V. L., DEDEMETER, D., Bateman, J. E. 1984; 15 (1): 91-93

  Abstract

  A 53-year-old man had the monomelic form of Ollier's disease, which resulted in deformity of the left leg. The patient was otherwise well until pain and increasing size of the left thigh led him to seek treatment. Biopsy revealed chondrosarcomatous transformation in the distal left femur. Hip disarticulation was performed. This case is unusual in that multiple foci of chondrosarcomatous transformation at various stages of development were present throughout the left femur, tibia, and fibula.

  View details for Web of Science ID A1984SA96700014

  View details for PubMedID 6693116

• SUPERVOLTAGE RADIOTHERAPY IN THE TREATMENT OF DIFFICULT GIANT-CELL TUMORS OF BONE CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Bell, R. S., Harwood, A. R., Goodman, S. B., Fornasier, V. L. 1983: 208-216

  Abstract

  Fifteen patients with giant cell tumor were treated by supervoltage radiotherapy. Each patient had been referred for therapy because adequate surgery would have been difficult or disfiguring. No patient who received appropriate therapy experienced a recurrence, and there were no cases of malignant transformation of a giant cell tumor after a mean follow-up period of 12 years. Radiotherapy is not recommended for primary treatment of giant cell tumor but may be indicated in exceptional circumstances.

  View details for Web of Science ID A1983QK71400029

  View details for PubMedID 6403271

• CASE REPORT-246 - OSTEOLYSIS OF THE ILIUM ASSOCIATED WITH A LOOSE ACETABULAR CUP FOLLOWING TOTAL HIP-ARTHROPLASTY, SECONDARY TO FOREIGN-BODY REACTION TO POLYETHYLENE AND METHYL-METHACRYLATE SKELETAL RADIOLOGY Bell, R. S., HAERI, G. B., Goodman, S. B., Fornasier, V. L. 1983; 10 (3): 201-204

  View details for Web of Science ID A1983RJ04400015

  View details for PubMedID 6356368

• COCCYGEAL GLOMUS TUMORS - A CASE OF MISTAKEN IDENTITY JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME Bell, R. S., Goodman, S. B., Fornasier, V. L. 1982; 64 (4): 595-597

  Abstract

  We undertook an anatomical and histological study to differentiate glomus-cell tumors of the pericoccygeal tissues from the normal coccygeal body. Removal of the coccyx was performed on five consecutive autopsy specimens from patients with no history of coccygeal symptoms. In each specimen, the coccygeal body (glomus coccygeum) was identified grossly and histologically. The histological appearance was indistinguishable from that of photomicrographs published in case reports of patients with glomus tumors of the coccyx. It is likely that the so-called tumors reported previously were in actuality normal glomus bodies.

  View details for Web of Science ID A1982NN96300016

  View details for PubMedID 6279672