All Publications

  • Immune profiling in orthopaedic diseases using mass cytometry : a narrative review of applications and future directions. Bone & joint research Susuki, Y., Thukkaram, M., Shinohara, I., Murayama, M., Morita, M., Igei, T., Ma, C., Pius, A. K., Gao, Q., Chow, S. K., Goodman, S. B. 2026; 15 (5): 497-507

    Abstract

    Musculoskeletal (MSK) diseases involve complex immune mechanisms. Conventional flow cytometry is restricted by spectral overlap, limiting multidimensional immune characterization. Mass cytometry by time-of-flight (CyTOF) can measure over 40 proteins per cell using metal-tagged antibodies and time-of-flight detection, providing deep immune phenotyping. The aim of this narrative review was to summarize the applications of CyTOF in the study of human orthopaedic and rheumatic diseases, highlight key immune findings including shared markers, and identify gaps to guide future research and panel standardization.A literature search of peer-reviewed studies published from 1 January 2014 to 31 December 2024 was conducted using PubMed, Scopus, and Web of Science. Search terms included "CyTOF" and "mass cytometry". Studies were included if CyTOF was applied to human MSK disorders with immune or inflammatory components and if the full text was available in English. Data extracted included disease type, sample source, computational pipeline, immune cell types analyzed, and main findings.A total of 22 studies were included. Since some studies reported results for more than one disease, the total number of disease-specific entries was 26: rheumatoid arthritis (n = 13), osteoarthritis (n = 4), psoriatic arthritis (n = 3), juvenile idiopathic arthritis (n = 2), ankylosing spondylitis (n = 1), idiopathic inflammatory myopathies (n = 1), and post-surgical immune monitoring (n = 2). Human models were represented. CyTOF identified disease-specific immune cell subsets, cytokine profiles, and treatment-response signatures. No eligible studies addressed osteoporosis or osteonecrosis likely reflecting that these conditions would yield low immune-cell density and/or technical challenges in acquiring bone tissue. Eight recurrent markers emerged across diseases: program cell death protein 1 (PD-1), inducible T-cell costimulator (ICOS), CXC motif chemokine receptor (CXCR)5, CXCR4, phosphorylated signal transducer and activator of transcription 4 protein (pSTAT3), tumour necrosis factor receptor II (TNFRII), p16 inhibitor of cyclin-dependent kinase 4a (p16INK4a), and cluster of differentiation (CD)180, which reflect shared pathways of inflammation, senescence, and tissue damage.CyTOF enables high-dimensional immune profiling in MSK diseases, offering insights into pathogenesis, treatment response, and patient stratification. Broader application of this technology to underexplored conditions is warranted. A minimal eight-marker backbone may enhance panel harmonization and support future multicentre translational studies in orthopaedic immunology.

    View details for DOI 10.1302/2046-3758.155.BJR-2025-0548.R1

    View details for PubMedID 42125857

  • Unsupervised Machine Learning Drives Dynamic Alignment Classification In Navigated Total Knee Arthroplasty. The Journal of arthroplasty Pius, A. K., Chinimilli, P. T., Angibaud, L. D., Jung, A., Jackson, C. A., Huddleston, J. I. 2026

    Abstract

    Current classifications used for total knee arthroplasty (TKA) are static and fail to capture the dynamic behavior of the limb during gait. This study introduces a novel intraoperative method to measure dynamic hip-knee angle (dHKA) using an intra-articular device coupled with a computer-assisted orthopaedic surgery (CAOS) system. This device applies a quasi-constant distraction force throughout the knee joint range of motion. A machine learning (ML) model was utilized to identify natural data groupings and develop a classification based on patient-specific dHKA profiles. We analyzed dHKA before and after the femoral cut (tibia-first TKA workflow) and assessed how often post-cut clusters matched pre-cut clusters across surgeons.A total of 1,890 tibia-first TKA cases performed by 11 surgeons were reviewed. For each case, HKA angles were recorded at 12 flexion angles (0 to 120°) before and after the femoral cut. Using pre-cut data, a 12-dimensional map was created with each dimension representing the degree of HKA at a specific flexion angle. A K-means clustering model was trained on data collected before the tibial cut to identify alignment profiles. The trained model was then applied to data collected after the tibial cut for comparison. A subset of 141 TKA cases from a single surgeon who had one-year Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS Jr.) scores was analyzed to explore the association between cluster preservation and early functional outcomes.Clustering evaluation identified four clusters and an 8-dimensional feature space as optimal. Pre-cut/post-cut cluster distributions were cluster one (15.3%/14.2%), cluster two (35.9%/30.1%), cluster three (34.2%/35.6%), and cluster four (14.5%/20.2%). Cluster one was characterized as valgus and neutral, cluster two as neutral, cluster three as low to moderate varus, and cluster four as moderate to high varus. Overall, 69.4% of the cases retained the same cluster post-cut, with surgeon-specific match rates ranging from 61 to 88%. In the outcomes subset, 72.3% preserved their pre-cut cluster. Preservation was associated with greater KOOS Jr. improvement, with cluster-specific significance observed in low-to-moderate varus knees.This study demonstrates the first use of unsupervised ML to classify intraoperative dHKA profiles captured with a force-controlled intra-articular device and CAOS system. This enables real-time feedback and offers a foundation for an automated alignment classification guidance in personalized TKA.

    View details for DOI 10.1016/j.arth.2026.04.091

    View details for PubMedID 42069019

  • Widening Gaps in Episode of Care Markers between Medicare Managed Care and Medicare Fee-for-Service in Spinal Fusion. The spine journal : official journal of the North American Spine Society Pius, A. K., Wong, H., Koltsov, J. C., Hu, S. S., Schoenfeld, A. J., Xiong, G. X. 2026

    Abstract

    Failure to accurately predict length of stay (LOS) and discharge disposition in the setting of spine fusion episodes of care can have substantial impact on patient care and resource allocation. Mandatory upcoming bundled payment models for spinal fusion will focus solely on Traditional Medicare beneficiaries; however, less is known about episode of care metrics in this subgroup compared with patients in other insurance classes.We sought to compare time-based trends among Traditional Medicare (TM) and Medicare Advantage (MA) in 1) LOS and home discharge, 2) readmission and emergency department visits, and 3) prevalence of medical comorbidities and social vulnerability.The Epic Cosmos dataset (comprising longitudinal records for over 300 million patients from over 1,700 hospitals) was used for this retrospective cohort study.Episodes of care containing single-level lumbar fusions performed in adults between January 1st, 2016, to December 31st, 2024.The primary outcome was length of stay in days. Secondary outcomes included rates of discharge home, 30-day readmission rates, and 30-day emergency department visits.Time-based trends and differences among primary insurance classes in LOS were assessed via a negative binomial regression model that included a two-way interaction between primary insurance class and time, with adjustment for sociodemographic, clinical, and institutional covariates. Primary insurance classes included Traditional Medicare, Medicare Advantage, Commercial, and Medicaid. Post-hoc tests were adjusted for multiple comparisons via the Holm-Bonferroni method.Among 126,304 spinal fusion episodes, LOS for TM patients decreased at an adjusted rate of 1.1% [(95% CI 0.4,1.7), p<0.001] faster per year compared with MA (TM: 2016-2024 unadjusted LOS 3.37-2.54; MA 3.53-3.12 days). Between 2016-2024, TM and MA both saw increases in home discharge, however by 2024 MA had higher adjusted rates of home discharge (unadjusted 2016-2024 raw rates TM 77.2-86.8%; MA 76.0-87.9%; adjusted 2024 rate 33% higher than TM [95% CI 18,51%, p < 0.001]). Over the study period, the MA cohort changed to become the group with the greatest number of Hierarchical Conditional Categories (2016 to 2024, 0.45-0.77; 15% increase compared to TM [10%, 22%, p < 0.001]). At the end of the study period, TM and Commercial had similar SVI (unadjusted 50th vs 50th percentile, adjusted p > 0.05) and MA and Medicaid had similar SVI (unadjusted 56th and 63rd percentile, adjusted p > 0.05). There were no differences in time-based trends between groups for readmission rates and emergency department visits.We observed longer LOS and increased home discharge rates with Medicare Advantage compared to Traditional Medicare over time without apparent improvements in readmission rates or emergency department visits. Traditional Medicare now has LOS and SVI approximating the commercially insured. The changes demonstrated in this study underscore widening gaps between Traditional Medicare and Medicare Advantage beneficiaries, despite the fact that upcoming mandatory bundled payment models will focus solely on Traditional Medicare beneficiaries. As Medicare Advantage becomes the dominant insurance class in the geriatric population, spine surgeons should be aware of patterns specific to Medicare Advantage patients, such as prolonged length of stay and increasing denials for post-acute care. Clinicians play a key role in setting patient expectations at the point-of-care and pre-surgical discharge planning may be important for certain subgroups.

    View details for DOI 10.1016/j.spinee.2026.01.022

    View details for PubMedID 41638363

  • Substantial Clinical Benefit After Total Knee Arthroplasty Has Been Set Too High: An Analysis of the American Joint Replacement Registry. The Journal of bone and joint surgery. American volume Zalikha, L., Chen, K. L., Pius, A. K., Sanchez, M., Zaniletti, I., Huddleston, J. I. 2026

    Abstract

    The U.S. Centers for Medicare & Medicaid Services (CMS) has set the substantial clinical benefit (SCB) for the Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) after primary total knee arthroplasty (TKA) at 20 points. We aimed to determine the percentages of patients who achieved the minimal clinically important difference (MCID) and the SCB for KOOS-JR at 1 year following TKA and to evaluate factors associated with benchmark achievement.We queried the American Joint Replacement Registry (AJRR) and screened 1,284,404 primary TKA cases performed from 2018 to 2023. We determined attainment of the KOOS-JR distribution-based MCID (7.5), anchor-based MCID (14), and SCB (20) at 12 months by each patient. Associations of covariates with the achievement of the MCIDs and the SCB were evaluated using a generalized linear model for binary outcomes that accounted for clustering within institutions. Unadjusted and adjusted odds ratios (ORs) for the outcomes of interest with 95% confidence intervals (CIs) were reported. Covariates included the preoperative KOOS-JR, sex, race or ethnicity, body mass index (BMI), Charlson Comorbidity Index (CCI), fixation type, use of technology, year of the procedure, region, institution type, teaching status, and number of beds.Linked scores were recorded by 64,773 patients. The mean patient age was 68.35 ± 8.60 years, 61.29% of patients were female, and 83.52% of patients were non-Hispanic White. The KOOS-JR threshold achievement rate was 86.8% for the calculated distribution-based MCID, 76.5% for the anchor-based MCID, and 65.7% for the SCB. Patients with higher preoperative scores (adjusted OR, 0.93 [95% CI, 0.93 to 0.93]; p < 0.001), Asian patients (adjusted OR, 0.59 [95% CI, 0.46 to 0.74]; p < 0.001), Black patients (adjusted OR, 0.55 [95% CI, 0.49 to 0.62]; p < 0.001), Hispanic patients (adjusted OR, 0.71 [95% CI, 0.51 to 0.99]; p = 0.042), non-Hispanic patients of other races (adjusted OR, 0.84 [95% CI, 0.74 to 0.95]; p = 0.007), male patients (adjusted OR, 0.89 [95% CI, 0.85 to 0.94]; p < 0.001), and patients with higher BMI (adjusted OR, 0.93 [95% CI, 0.87 to 0.99]; p = 0.025) showed lower odds of achieving the SCB. A CCI of ≥5 was additionally found to be associated with lower odds of achieving the distribution-based MCID (adjusted OR, 0.89 [95% CI, 0.79 to 0.99]; p = 0.032) and anchor-based MCID (adjusted OR, 0.89 [95% CI, 0.81 to 0.97]; p = 0.012).The CMS relatively arbitrarily defined the SCB at a value that is too high for an operation that routinely yields >80% patient satisfaction.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

    View details for DOI 10.2106/JBJS.25.00952

    View details for PubMedID 41610198

  • Understanding the radiographic anatomy of the patella to avoid placement of intra-articular implants. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Pius, A., Cruz, J., Tedesco, C., Skaggs, K., Hunt, A., Goodnough, H., Gardner, M., Bishop, J. 2025; 35 (1): 411

    Abstract

    PURPOSE: To map the articular margins of the patella and quantify an "at-risk" zone for intra-articular implant placement during fixation of patella fractures.METHODS: This was an observational cadaveric study utilizing eight fresh frozen adult knee specimens. Radiopaque wire was applied to the articular margins of the medial and lateral patellar facets and the center apical ridge. Fluoroscopic images were obtained and examined to identify radiographic "at-risk" zones for intra-articular surgical implants.RESULTS: Radiographically, the medial and lateral facets were deep to the central ridge on all specimens. The articular margin of the lateral facet was on average 11.4mm (range 5.9-14.5mm, SD 2.8mm) anterior to the apex of the center ridge. The articular margin of the medial facet was on average 7.45mm (range 2.0-11.6mm, SD 3.5mm) anterior to the apex of the central ridge. On average, the depth of the medial and lateral facets occupied 31.5% and 53.1% of the total patellar depth (measured from the anterior cortex to the central articular ridge).CONCLUSION: The articular margins of the medial and lateral facets of the patella are difficult to distinguish radiographically. When viewed on a lateral radiograph, the surgical "at-risk" zones of the medial and lateral patella exist between 33% (one-third) and 50% (one half) of the total patellar depth when measured from the articular surface. Implants placed within this zone have the potential to be intra-articular.

    View details for DOI 10.1007/s00590-025-04525-9

    View details for PubMedID 41037109

  • Metformin Modulates Oxidative Stress in Murine Mesenchymal Stem Cells In Vitro and Alleviates Corticosteroid-Induced Inflammation and Impairment of Bone Formation HSS JOURNAL Shinohara, I., Susuki, Y., Murayama, M., Gao, Q., Cekuc, M., Ergul, Y., Morita, M., Pius, A. K., Ma, C., Chow, S., Goodman, S. B. 2025

    View details for DOI 10.1177/15563316251351031

    View details for Web of Science ID 001526669500001

  • Metformin Modulates Oxidative Stress in Murine Mesenchymal Stem Cells In Vitro and Alleviates Corticosteroid-Induced Inflammation and Impairment of Bone Formation. HSS journal : the musculoskeletal journal of Hospital for Special Surgery Shinohara, I., Susuki, Y., Murayama, M., Gao, Q., Cekuc, M. S., Ergul, Y. S., Morita, M., Pius, A. K., Ma, C., Chow, S. K., Goodman, S. B. 2025: 15563316251351031

    Abstract

    Long-term use of corticosteroids is a known risk factor for various bone diseases. Corticosteroids disrupt the balance between oxidative and glycolytic energy metabolism, increase oxidative stress and reactive oxygen species (ROS) associated with prolongation of inflammation, cell apoptosis, deficits in mesenchymal stem cells (MSCs), and osteoclast differentiation. Metformin, a drug for diabetes, has antioxidant properties by inhibiting nicotinamide adenine dinucleotide phosphate oxidase, which promotes the production of ROS.We sought to evaluate the effects of corticosteroid and metformin administration on MSCs in vitro.Primary bone marrow MSCs were collected from 20 mice. We evaluated prednisolone's effects on cell proliferation, oxidative stress, osteogenic differentiation, and mineralization, followed by metformin's effect on corticosteroid-induced reduction in bone formation. Metformin (1, 10, 100 µM) was tested with prednisolone 3 ng/mL. Cytokines were assessed by Luminex.Prednisolone at 3 ng/mL significantly reduced cell proliferation, while 10 µM metformin restored it. Prednisolone increased oxidative stress and was reversed by metformin in a concentration-dependent manner, particularly at 100 µM. Osteogenic differentiation and mineralization were significantly impaired with prednisolone but improved with metformin at 10 and 100 µM. As for inflammatory cytokines, interleukin-1β (IL-1β) expression was increased by prednisolone administration and suppressed by metformin. Conversely, IL-6 and monocyte chemotactic protein-1 were suppressed by prednisolone.This in vitro study found that corticosteroid-associated decrease in osteogenic potential of murine MSCs was associated with elevated oxidative stress that can be alleviated by metformin; further studies are needed to validate these findings in vivo and with human-derived MSCs.

    View details for DOI 10.1177/15563316251351031

    View details for PubMedID 40661872

    View details for PubMedCentralID PMC12255654

  • Short-term outcomes of locking mini-fragment plate fixation for treatment of Vancouver B2 periprosthetic femur fractures. European journal of orthopaedic surgery & traumatology : orthopedie traumatologie Lee, M. L., Pius, A. K., Goodnough, L. H. 2025; 35 (1): 288

    Abstract

    The purpose of the study is to evaluate the safety and efficacy of mini-fragment plate fixation of trochanteric fragments in Vancouver B2 femur fractures. Pre-contoured plates are generally used in the proximal femur of Vancouver B2 fractures to secure trochanteric fragments. However, stout pre-contoured plates are a potential source of symptomatic implants in a sensitive location, and alternatives such as mini-fragment fixation have not yet been reported.In this case series, we retrospectively reviewed 5 patients who underwent operative treatment of Vancouver B2 periprosthetic femur fractures with locking mini-fragment plate fixation. Demographic and clinical variables were recorded for all patients. Outcome measures including post operative dislocation, infection, mortality, additional procedures, malunion or nonunion, fixation failure, time to ambulation, and instability were recorded and compared to historical alternatives, such as fixation with pre-contoured plates.No patients experienced fixation failure, nonunion or malunion, or underwent reoperation. One patient died postoperatively due to medical comorbidities. One patient developed mild hip pain around the implant postoperatively with no need for revision.Mini-fragment plate fixation demonstrated no incidence of fixation failure or nonunion and is safe in the treatment of Vancouver B2 periprosthetic femur fractures. This technique represents a promising alternative in the management of Vancouver B2 periprosthetic femur fractures for surgeons hoping to avoid symptomatic implants without compromising fixation.

    View details for DOI 10.1007/s00590-025-04408-z

    View details for PubMedID 40603601

    View details for PubMedCentralID 10499103

  • Optimization of Cytometry by Time-of-Flight Staining for Peripheral Blood and Bone Marrow Samples. Tissue engineering. Part C, Methods Susuki, Y., Shinohara, I., Murayama, M., Morita, M., Ma, C., Pius, A. K., Gao, Q., Chow, S. K., Goodman, S. B. 2025; 31 (7): 261-270

    Abstract

    Cytometry by time-of-flight (CyTOF) enables comprehensive immune profiling for translational research. However, challenges such as signal variability, nonspecific binding, and antibody incompatibility can compromise data quality. This study presents an optimized CyTOF staining protocol for human peripheral blood mononuclear cells and bone marrow aspiration concentrate samples, addressing these challenges by refining antibody conjugation with polymer X8, saponin use, and fixation protocols. Preliminary data indicate improved staining for key markers (CD14, CD16, and CD19), enhancing signal consistency and clarity. These findings advance the utility of CyTOF in orthopaedic research and immune profiling for diseases such as osteonecrosis of the femoral head.

    View details for DOI 10.1177/19373341251360986

    View details for PubMedID 40690723

  • Navigated and Robotic Total Knee Arthroplasty Do Not Confer Improved 5-Year Survivorship Compared to Conventional TKA: An Analysis from the American Joint Replacement Registry. The Journal of arthroplasty Pius, A. K., Sporer, S. M., Sterling, O., De, M., Jahan, M., Browne, J. A., Springer, B. D., Huddleston, J. I. 2025

    Abstract

    Computer-assisted navigation (nTKA) and/or the use of robotics (rTKA) at the time of the primary total knee arthroplasty have been shown to improve implant position, minimize alignment outliers, and possibly improve patient outcomes compared to conventional instrumentation (cTKA). The purpose of this study was to use the linked Medicare dataset from the American Joint Replacement Registry (AJRR) to compare the mid-term (five-year) outcomes of nTKA and rTKA to those of cTKA.All primary TKA procedures submitted to AJRR between January 2017 and December 2022 among patients aged 65 years and older were included in the analysis. The data were stratified into patients who underwent nTKA, rTKA, or cTKA at the time of their index procedure. The all-cause revision rate, mechanical loosening rate, and the other mechanical complication rate were determined at five years postoperatively. The survival model was adjusted for age, sex, fixation type, and year.At five years postoperatively, the survival model found computer navigation use to not be significant in TKA all-cause revision (P = 0.32) or mechanical loosening (P = 0.91) but was significant for other mechanical complications (P = 0.004). Robotic use was not found to be significant in TKA all-cause revision (P = 0.75), mechanical loosening (P = 0.42), or other mechanical complications (P = 0.46).Navigation and/or the use of robotics at the time of primary total knee arthroplasty did not demonstrate a decrease in the need for revision at mid-term (5-year) follow-up among Medicare beneficiaries. While this study was unable to assess other important clinical outcomes following total knee arthroplasty with advanced technology, the purported benefits of utilizing this technology to improve component survival are not supported.

    View details for DOI 10.1016/j.arth.2025.03.047

    View details for PubMedID 40139479

  • 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

  • 3D Culture of MSCs for Clinical Application BIOENGINEERING-BASEL Gao, Q., Cekuc, M., Ergul, Y., Pius, A. K., Shinohara, I., Murayama, M., Susuki, Y., Ma, C., Morita, M., Chow, S., Goodman, S. B. 2024; 11 (12)

    View details for DOI 10.3390/bioengineering11121199

    View details for Web of Science ID 001386779800001

  • 3D Culture of MSCs for Clinical Application. Bioengineering (Basel, Switzerland) Gao, Q., Cekuc, M. S., Ergul, Y. S., Pius, A. K., Shinohara, I., Murayama, M., Susuki, Y., Ma, C., Morita, M., Chow, S. K., Goodman, S. B. 2024; 11 (12)

    Abstract

    Mesenchymal stem cells (MSCs) play an important role in regenerative medicine and drug discovery due to their multipotential differentiation capabilities and immunomodulatory effects. Compared with traditional 2D cultures of MSCs, 3D cultures of MSCs have emerged as an effective approach to enhance cell viability, proliferation, and functionality, and provide a more relevant physiological environment. Here, we review the therapeutic potential of 3D-cultured MSCs, highlighting their roles in tissue regeneration and repair and drug screening. We further summarize successful cases that apply 3D MSCs in modeling disease states, enabling the identification of novel therapeutic strategies. Despite these promising applications, we discuss challenges that remain in the clinical translation of 3D MSC technologies, including stability, cell heterogeneity, and regulatory issues. We conclude by addressing these obstacles and emphasizing the need for further research to fully exploit the potential of 3D MSCs in clinical practice.

    View details for DOI 10.3390/bioengineering11121199

    View details for PubMedID 39768017

  • The Advantages and Shortcomings of Stem Cell Therapy for Enhanced Bone Healing TISSUE ENGINEERING PART C-METHODS Chow, S., Gao, Q., Pius, A., Morita, M., Ergul, Y., Murayama, M., Shinohara, I., Cekuc, M., Ma, C., Susuki, Y., Goodman, S. B. 2024; 30 (10): 415-430

    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 Web of Science ID 001325811000001

    View details for PubMedID 39311464

  • 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

  • Patient Acceptance of Reoperation Risk for Lumbar Decompression Versus Fusion. The spine journal : official journal of the North American Spine Society Pius, A. K., Joseph, Y. D., Mullis, D. M., Koduri, J., Levin, J., Alamin, T. F. 2024

    Abstract

    Lumbar decompression and lumbar fusion are effective methods of treating spinal compressive pathologies refractory to conservative management. These surgeries are typically used to treat different spinal problems, but there is a growing body of literature investigating the outcomes of either approach for patients with lumbar degenerative spondylolisthesis and stenosis. Different operations are associated with different risks and different potential needs for reoperation. Patient acceptance of reoperation rates after spinal surgery is currently not well understood.The purpose of this study is to identify patient tolerance for reoperation rates following lumbar decompression and lumbar fusion surgery.A qualitative and quantitative survey intended to capture information on patient preferences was administered.Written informed consent was obtained from patients presenting to two spinal clinics.Patients were asked their threshold tolerance for reoperation rates in the context of choosing a smaller (decompression) versus larger (fusion) spinal surgery.A survey was administered to patients at two spinal clinics-one surgical and one non-surgical. A consecutive series of new patients over multiple clinic days who agreed to participate in the study and filled out the survey are reported on here. Patients were asked to assess, contemplating a problem that could either be treated with lumbar decompression or lumbar fusion, the level at which 1) the likelihood that needing a repeat surgery within 3-5 years would change their mind about choosing the decompression operation and cause them to choose the fusion operation and then 2) the likelihood of needing a repeat surgery within 3-5 years that would be acceptable to them after the fusion operation. The distribution of patient responses was assessed with histograms and descriptive statistics.Ninety patients were surveyed, and of these, 73 patients (81.1%) returned fully completed questionnaires. The median reoperation acceptance rates after a decompression was <60%, while the median acceptable revision rate when contemplating the fusion surgery was 10%.Patient acceptance for the potential need for revision surgery is higher when considering a decompression compared to a fusion operation. Reoperation risk rates along with the magnitude of the surgical intervention are important considerations in determining patients' surgical preferences. Understanding patient preferences and risk tolerances can aid clinicians in shared decision-making, potentially improving patient satisfaction and outcomes in the several lumbar pathologies which can be ameliorated with either decompression or fusion.

    View details for DOI 10.1016/j.spinee.2024.09.003

    View details for PubMedID 39303829

  • 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

  • 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

  • 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