All Publications


  • Denervation during mandibular distraction osteogenesis results in impaired bone formation. Scientific reports Tevlin, R., Griffin, M., Chen, K., Januszyk, M., Guardino, N., Spielman, A., Walters, S., Gold, G. E., Chan, C. K., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2023; 13 (1): 2097

    Abstract

    Mandibular distraction osteogenesis (DO) is mediated by skeletal stem cells (SSCs) in mice, which enact bone regeneration via neural crest re-activation. As peripheral nerves are essential to progenitor function during development and in response to injury, we questioned if denervation impairs mandibular DO. C57Bl6 mice were divided into two groups: DO with a segmental defect in the inferior alveolar nerve (IAN) at the time of mandibular osteotomy ("DO Den") and DO with IAN intact ("DO Inn"). DO Den demonstrated significantly reduced histological and radiological osteogenesis relative to DO Inn. Denervation preceding DO results in reduced SSC amplification and osteogenic potential in mice. Single cell RNA sequencing analysis revealed that there was a predominance of innervated SSCs in clusters dominated by pathways related to bone formation. A rare human patient specimen was also analyzed and suggested that histological, radiological, and transcriptional alterations seen in mouse DO may be conserved in the setting of denervated human mandible distraction. Fibromodulin (FMOD) transcriptional and protein expression were reduced in denervated relative to innervated mouse and human mandible regenerate. Finally, when exogenous FMOD was added to DO-Den and DO-Inn SSCs undergoing in vitro osteogenic differentiation, the osteogenic potential of DO-Den SSCs was increased in comparison to control untreated DO-Den SSCs, modeling the superior osteogenic potential of DO-Inn SSCs.

    View details for DOI 10.1038/s41598-023-27921-9

    View details for PubMedID 36747028

  • Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting. Science translational medicine Chen, K., Henn, D., Januszyk, M., Barrera, J. A., Noishiki, C., Bonham, C. A., Griffin, M., Tevlin, R., Carlomagno, T., Shannon, T., Fehlmann, T., Trotsyuk, A. A., Padmanabhan, J., Sivaraj, D., Perrault, D. P., Zamaleeva, A. I., Mays, C. J., Greco, A. H., Kwon, S. H., Leeolou, M. C., Huskins, S. L., Steele, S. R., Fischer, K. S., Kussie, H. C., Mittal, S., Mermin-Bunnell, A. M., Diaz Deleon, N. M., Lavin, C., Keller, A., Longaker, M. T., Gurtner, G. C. 2022; 14 (645): eabj9152

    Abstract

    Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

    View details for DOI 10.1126/scitranslmed.abj9152

    View details for PubMedID 35584231

  • Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis. Nature communications Menon, S., Salhotra, A., Shailendra, S., Tevlin, R., Ransom, R. C., Januszyk, M., Chan, C. K., Behr, B., Wan, D. C., Longaker, M. T., Quarto, N. 2021; 12 (1): 4640

    Abstract

    Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cellsderived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. Crossing Axin2LacZ/+ mouse, endowing enhanced Wnt activation, to a Twist1+/- mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy in Twist1+/- mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.

    View details for DOI 10.1038/s41467-021-24801-6

    View details for PubMedID 34330896

  • Disrupting biological sensors of force promotes tissue regeneration in large organisms. Nature communications Chen, K., Kwon, S. H., Henn, D., Kuehlmann, B. A., Tevlin, R., Bonham, C. A., Griffin, M., Trotsyuk, A. A., Borrelli, M. R., Noishiki, C., Padmanabhan, J., Barrera, J. A., Maan, Z. N., Dohi, T., Mays, C. J., Greco, A. H., Sivaraj, D., Lin, J. Q., Fehlmann, T., Mermin-Bunnell, A. M., Mittal, S., Hu, M. S., Zamaleeva, A. I., Keller, A., Rajadas, J., Longaker, M. T., Januszyk, M., Gurtner, G. C. 2021; 12 (1): 5256

    Abstract

    Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.

    View details for DOI 10.1038/s41467-021-25410-z

    View details for PubMedID 34489407

  • Aged skeletal stem cells generate an inflammatory degenerative niche. Nature Ambrosi, T. H., Marecic, O., McArdle, A., Sinha, R., Gulati, G. S., Tong, X., Wang, Y., Steininger, H. M., Hoover, M. Y., Koepke, L. S., Murphy, M. P., Sokol, J., Seo, E. Y., Tevlin, R., Lopez, M., Brewer, R. E., Mascharak, S., Lu, L., Ajanaku, O., Conley, S. D., Seita, J., Morri, M., Neff, N. F., Sahoo, D., Yang, F., Weissman, I. L., Longaker, M. T., Chan, C. K. 2021

    Abstract

    Loss of skeletal integrity during ageing and disease is associated with an imbalance in the opposing actions of osteoblasts and osteoclasts1. Here we show that intrinsic ageing of skeletal stem cells (SSCs)2 in mice alters signalling in the bone marrow niche and skews the differentiation of bone and blood lineages, leading to fragile bones that regenerate poorly. Functionally, aged SSCs have a decreased bone- and cartilage-forming potential but produce more stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell RNA-sequencing studies link the functional loss to a diminished transcriptomic diversity of SSCs in aged mice, which thereby contributes to the transformation of the bone marrow niche. Exposure to a youthful circulation through heterochronic parabiosis or systemic reconstitution with young haematopoietic stem cells did not reverse the diminished osteochondrogenic activity of aged SSCs, or improve bone mass or skeletal healing parameters in aged mice. Conversely, the aged SSC lineage promoted osteoclastic activity and myeloid skewing by haematopoietic stem and progenitor cells, suggesting that the ageing of SSCs is a driver of haematopoietic ageing. Deficient bone regeneration in aged mice could only be returned to youthful levels by applying a combinatorial treatment of BMP2 and a CSF1 antagonist locally to fractures, which reactivated aged SSCs and simultaneously ablated the inflammatory, pro-osteoclastic milieu. Our findings provide mechanistic insights into the complex, multifactorial mechanisms that underlie skeletal ageing and offer prospects for rejuvenating the aged skeletal system.

    View details for DOI 10.1038/s41586-021-03795-7

    View details for PubMedID 34381212

  • Immediate targeted nipple-areolar complex re-innervation: Improving outcomes in immediate autologous breast reconstruction. Journal of plastic, reconstructive & aesthetic surgery : JPRAS Tevlin, R. n., Brazio, P. n., Tran, N. n., Nguyen, D. n. 2020

    Abstract

    Breast reconstruction often renders the chest skin and nipple areolar complex (NAC) insensate. We propose a new technique of preserving the intercostal nerves during mastectomy and using them to reinnervate the NAC following mastectomy and immediate autologous tissue reconstruction. The technique involves preservation of the lateral intercostal nerves during mastectomy, dissection of the lateral intercostal nerves to length, coaptation of the intercostal nerves to a nerve graft which is then tunneled through the free flap and the distal nerve graft is then coapted to the nerve stumps at the base of the NAC. We performed a retrospective analysis of 14 breasts, which underwent nipple reinnervation during immediate autologous breast reconstruction. Mean age was 49 years (range: 32-61 years). Sensory outcomes, as tested with Semmes-Weinstein monofilaments, were compared to a cohort of breasts that underwent nipple sparing mastectomy without neurotization. Compared to control patients, there was no statistically significant difference (p = 0.0969) in sensation between pre-operative and post-operative nipple sensation at final follow-up. This proof-of-concept study suggests that immediate re-innervation of the NAC in the setting of immediate breast reconstruction enhances recovery of the NAC sensation.

    View details for DOI 10.1016/j.bjps.2020.11.021

    View details for PubMedID 33341386

  • Pharmacological rescue of diabetic skeletal stem cell niches. Science translational medicine Tevlin, R., Seo, E. Y., Marecic, O., McArdle, A., Tong, X., Zimdahl, B., Malkovskiy, A., Sinha, R., Gulati, G., Li, X., Wearda, T., Morganti, R., Lopez, M., Ransom, R. C., Duldulao, C. R., Rodrigues, M., Nguyen, A., Januszyk, M., Maan, Z., Paik, K., Yapa, K., Rajadas, J., Wan, D. C., Gurtner, G. C., Snyder, M., Beachy, P. A., Yang, F., Goodman, S. B., Weissman, I. L., Chan, C. K., Longaker, M. T. 2017; 9 (372)

    Abstract

    Diabetes mellitus (DM) is a metabolic disease frequently associated with impaired bone healing. Despite its increasing prevalence worldwide, the molecular etiology of DM-linked skeletal complications remains poorly defined. Using advanced stem cell characterization techniques, we analyzed intrinsic and extrinsic determinants of mouse skeletal stem cell (mSSC) function to identify specific mSSC niche-related abnormalities that could impair skeletal repair in diabetic (Db) mice. We discovered that high serum concentrations of tumor necrosis factor-α directly repressed the expression of Indian hedgehog (Ihh) in mSSCs and in their downstream skeletogenic progenitors in Db mice. When hedgehog signaling was inhibited during fracture repair, injury-induced mSSC expansion was suppressed, resulting in impaired healing. We reversed this deficiency by precise delivery of purified Ihh to the fracture site via a specially formulated, slow-release hydrogel. In the presence of exogenous Ihh, the injury-induced expansion and osteogenic potential of mSSCs were restored, culminating in the rescue of Db bone healing. Our results present a feasible strategy for precise treatment of molecular aberrations in stem and progenitor cell populations to correct skeletal manifestations of systemic disease.

    View details for DOI 10.1126/scitranslmed.aag2809

    View details for PubMedID 28077677

  • Identification and characterization of an injury-induced skeletal progenitor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Marecic, O., Tevlin, R., McArdle, A., Seo, E. Y., Wearda, T., Duldulao, C., Walmsley, G. G., Nguyen, A., Weissman, I. L., Chan, C. K., Longaker, M. T. 2015; 112 (32): 9920-9925

    Abstract

    The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized that skeletal progenitor cells active during these disparate phases are genetically and phenotypically distinct. We identified a highly potent regenerative cell type that we term the fracture-induced bone, cartilage, stromal progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses significantly enhanced skeletogenic potential compared with BCSPs harvested from uninjured bone. It also recapitulates many gene expression patterns involved in perinatal skeletogenesis. Our results indicate that the skeletal progenitor population is functionally stratified, containing distinct subsets responsible for growth, regeneration, and repair. Furthermore, our findings suggest that injury-induced changes to the skeletal stem and progenitor microenvironments could activate these cells and enhance their regenerative potential.

    View details for DOI 10.1073/pnas.1513066112

    View details for PubMedID 26216955

  • Identification and specification of the mouse skeletal stem cell. Cell Chan, C. K., Seo, E. Y., Chen, J. Y., Lo, D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T., Lu, W., Senarath-Yapa, K., Chung, M. T., Marecic, O., Tran, M., Yan, K. S., Upton, R., Walmsley, G. G., Lee, A. S., Sahoo, D., Kuo, C. J., Weissman, I. L., Longaker, M. T. 2015; 160 (1-2): 285-298

    Abstract

    How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs in situ, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

    View details for DOI 10.1016/j.cell.2014.12.002

    View details for PubMedID 25594184

  • Single-Cell RNA-Sequencing Identifies Modulator of Foreign Body Response with Use of Acellular Dermal Matrix in Breast Reconstruction Liang, N., Tevlin, R., Griffin, M., Parker, J. B., Henn, D., Navarro, R. S., Dung Nguyen, Momeni, A., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2023: S389-S390
  • Technical Tips to Reduce Implant Rippling in Staged Pre-pectoral Breast Reconstruction. Aesthetic plastic surgery Tevlin, R., Sharma, A. D., Griffin, M., Wan, D., Momeni, A. 2023

    Abstract

    INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) is becoming increasingly popular, permitting optimal implant positioning on the chest wall, prevention of animation deformity, and reduced patient discomfort. There are, however, concerns related to increased rates of breast implant rippling in pre-pectoral (versus submuscular) IBR, which can prompt a patient to seek revisionary surgery. The aim of this study is to identify factors that can be implemented to reduce implant rippling in the setting of pre-pectoral IBR.METHODS: A literature review was conducted using the PubMed database to determine the rate of rippling in pre-pectoral IBR. Clinical studies in English were included. Further review was then performed to explore technical strategies associated with reduced rates of rippling in pre-pectoral two-stage breast reconstruction.RESULTS: Implant rippling has been reported with a rate varying from 0 to 53.8% in 25 studies of pre-pectoral IBR (including both direct-to-implant and two-stage IBR). The majority of studies reviewed did not demonstrate a significant association between BMI and rippling, suggesting that other factors, likely technical and device-related, contribute to the manifestation of implant rippling. Hence, we explored whether specific technical modifications could be implemented that would reduce the risk of rippling in patients undergoing pre-pectoral IBR. Specifically, we highlight the need for close attention to expansion protocol and pocket dimension, expander fill medium and implant characteristics, and the rationale behind adjunctive procedures to reduce implant rippling.CONCLUSION: Surgical modifications may reduce the incidence of rippling in pre-pectoral breast reconstruction.LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

    View details for DOI 10.1007/s00266-023-03616-4

    View details for PubMedID 37704858

  • Large Language Models and Artificial Intelligence: A Primer for Plastic Surgeons on the Demonstrated & Potential Applications, Promises, and Limitations of ChatGPT. Aesthetic surgery journal Abi-Rafeh, J., Xu, H. H., Kazan, R., Tevlin, R., Furnas, H. 2023

    Abstract

    BACKGROUND: The rapidly evolving field of artificial intelligence (AI) holds great potential for plastic surgeons. ChatGPT, a recently released AI large language model (LLM), promises application across many disciplines, including healthcare.OBJECTIVES: The aim of this article is to provide a plastic surgeon's primer on AI, LLM, and ChatGPT, including an analysis of current demonstrated and proposed clinical applications.METHODS: A systematic review was performed identifying medical and surgical literature on ChatGPT's proposed clinical applications. Variables assessed included applications investigated, command tasks provided, user input information, AI-emulated human skills, output validation, and reported limitations.RESULTS: The analysis included 175 articles reporting on 13 plastic surgery applications and 116 additional clinical applications, categorized by field and purpose. Thirty-four plastic surgery applications were varied in their target audience, including attending plastic surgeons (n=17, 50%), trainees/educators (n=8, 24.0%), researchers/scholars (n=7, 21%), and patients (n=2, 6%). The 15 identified limitations of ChatGPT were categorized by training data, algorithm, and ethical considerations.CONCLUSIONS: Widespread use of ChatGPT in plastic surgery will depend on rigorous research of proposed applications to validate performance and address limitations. This systemic review aims to guide research, development, and regulation to safely adopt AI in plastic surgery.

    View details for DOI 10.1093/asj/sjad260

    View details for PubMedID 37562022

  • Developing a Mouse Model to Evaluate Tibial Distraction Osteogenesis DiIorio, S., Tevlin, R., Shah, H. N., Salhotra, A., Griffin, M., Januszyk, M., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2023: S90
  • An Inexpensive 3D Printed Mouse Model of Successful, Complication-free Long Bone Distraction Osteogenesis. Plastic and reconstructive surgery. Global open Tevlin, R., Shah, H. N., Salhotra, A., Di Iorio, S. E., Griffin, M., Januszyk, M., Wan, D. C., Longaker, M. T. 2023; 11 (2): e4674

    Abstract

    Distraction osteogenesis (DO) is used for skeletal defects; however, up to 50% of cases exhibit complications. Previous mouse models of long bone DO have been anecdotally hampered by postoperative complications, expense, and availability. To improve clinical techniques, cost-effective, reliable animal models are needed. Our focus was to develop a new mouse tibial distractor, hypothesized to result in successful, complication-free DO.A lightweight tibial distractor was developed using CAD and 3D printing. The device was fixed to the tibia of C57Bl/6J mice prior to osteotomy. Postoperatively, mice underwent 5 days latency, 10 days distraction (0.15 mm every 12 hours), and 28 days consolidation. Bone regeneration was examined on postoperative day 43 using micro-computed tomography (μCT) and Movat's modified pentachrome staining on histology (mineralized volume fraction and pixels, respectively). Costs were recorded. We compared cohorts of 11 mice undergoing sham, DO, or acute lengthening (distractor acutely lengthened 3.0 mm).The histological bone regenerate was significantly increased in DO (1,879,257 ± 155,415 pixels) compared to acute lengthening (32847 ± 1589 pixels) (P < 0.0001). The mineralized volume fraction (bone/total tissue volume) of the regenerate was significantly increased in DO (0.9 ± 0.1) compared to acute lengthening (0.7 ± 0.1) (P < 0.001). There was no significant difference in bone regenerate between DO and sham. The distractor was relatively low cost ($11), with no complications.Histology and µCT analysis confirmed that the proposed tibial DO model resulted in successful bone formation. Our model is cost-effective and reproducible, enabling implementation in genetically dissectible transgenic mice.

    View details for DOI 10.1097/GOX.0000000000004674

    View details for PubMedID 36798717

    View details for PubMedCentralID PMC9925097

  • Investigating the Severity of Complications following Nipple-sparing Mastectomy and Immediate Prepectoral Implant-based vs. Autologous Reconstruction - A Single-Surgeon Experience. Plastic and reconstructive surgery Pedreira, R., Tevlin, R., Griffin, M., Wan, D., Momeni, A. 2022

    Abstract

    Several clinical studies have reported autologous breast reconstruction (ABR) to be associated with a higher postoperative complication rate; however, few have investigated the impact of reconstructive modality on complication severity. This study examines the impact of reconstructive modality on complication severity in a matched cohort of patients who underwent ABR versus implant-based breast reconstruction (IBR).A retrospective study of patients who underwent nipple-sparing mastectomy with immediate reconstruction was performed. Propensity score matching (PSM) ensured adequate matching of patients who underwent ABR and staged prepectoral IBR, respectively. Patient demographics, breast measurements and postoperative outcomes, including the incidence and severity of complications were analyzed. Multivariable logistic regression analysis was performed. A P-value of <0.05 was considered significant.128 patients (214 breast reconstructions) were included for analysis (ABR n = 64; IBR n = 64). No difference in overall complication rate was noted (p = 0.61). However, a significant association of IBR with major complications was noted (p = 0.02). In contrast, minor complications were significantly more frequent following ABR (p = 0.04).While the reconstructive modality did not appear to have an effect on the overall complication rate, it did significantly affect the severity of postoperative complications with major and minor complications being associated with IBR and ABR, respectively. These findings are relevant to patient-centered decision-making as they provide further granularity regarding postoperative complications and address the issue of complication severity.

    View details for DOI 10.1097/PRS.0000000000009827

    View details for PubMedID 36332003

  • Denervation During Mouse and Human Mandibular Distraction Osteogenesis Results in Impaired Osteogenesis Tevlin, R., Griffin, M., Chen, K., Januszyk, M., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2022: S202
  • Peripheral Nerve Injury After Upper-Extremity Surgery Performed Under Regional Anesthesia: A Systematic Review. Journal of hand surgery global online Silverstein, M. L., Tevlin, R., Higgins, K. E., Pedreira, R., Curtin, C. 2022; 4 (4): 201-207

    Abstract

    Purpose: Peripheral nerve injury (PNI) is a known adverse event following upper-limb surgery performed under brachial plexus regional anesthesia (RA). When PNI is noted after surgery, patients and providers often have questions about which factors might have contributed to this complication. This systematic review evaluates the literature on hand and shoulder surgeries performed under ultrasound-guided, plexus RA to identify factors potentially associated with PNI, including the surgery location and block type. We hypothesized that shoulder surgery might be associated with an increased risk of PNI compared to hand surgery.Methods: A systematic review of the relevant literature was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only prospective studies on the use of ultrasound-guided, preoperative, brachial plexus RA for hand or shoulder surgery on adult patients were included. Study groups were categorized according to surgery location and block type and compared across a number of factors via univariate and multivariate analyses.Results: A total of 3,037 abstracts were screened; 192 full-text articles were independently reviewed by 2 of the authors; and 53 studies were included in the systematic review analysis. Following hand surgery, PNI was reported at an average rate of 1.35% ± 3.21% across 836 subjects in 40 study groups; after shoulder surgery, the average rate was 0.50% ± 1.57% across 3,383 subjects in 15 study groups. There was no statistically significant correlation between the incidence of PNI and surgery location (P=.70) or any of the most common approaches for brachial plexus anesthesia in the multivariate analysis.Conclusions: This systematic review of over 50 articles on upper-limb surgery performed under RA shows no association between the incidence of PNI and the location of surgery or type of brachial plexus block.Type of study/level of evidence: Diagnostic II.

    View details for DOI 10.1016/j.jhsg.2022.04.011

    View details for PubMedID 35880155

  • Smooth versus textured tissue expanders in breast reconstruction - A retrospective review of post-operative surgical site infections. Journal of plastic, reconstructive & aesthetic surgery : JPRAS Tevlin, R., Cemaj, S. L., Azad, A. D., Borrelli, M. R., Silverstein, M. L., Posternak, V., Nguyen, D., Lee, G. K., Nazerali, R. S. 2022

    Abstract

    Textured tissue expanders (TTEs) were introduced to limit migration and reduce capsular contracture, which were inherent to smooth tissue expanders (STEs). Previous reports suggest that textured devices have increased rates of bacterial contamination and biofilm formation in comparison with smooth devices. Recently, the relative increased association of anaplastic large cell lymphoma (ALCL) with textured versus smooth devices has led to increased adoption of smooth devices. The aim of our study is to evaluate the post-operative surgical site infection (SSI) rates of STEs versus TTEs.A retrospective case series was conducted at a single academic teaching hospital from April 2016 to December 2019. The primary outcome variable was the development of a post-operative SSI.One hundred seventy-seven breasts underwent reconstruction with TTEs and 109 breasts underwent reconstruction with STE. In total, 54 SSIs were recorded (n = 34 TTE; n = 20 STE), with the majority of infections occurring within the first 30 post-operative days (TTE 65%, STE 70%). There was no statistically significant difference in overall post-operative infection rates between TTE and STE groups when broken down into the following time points: <30 day, 30-60 days, and >90 days (p = 0.924). There was no statistically significant difference between infection type (superficial vs. deep, p = 0.932), infection management (medical, surgical, or both, p = 0.409) or salvage results (p = 0.078) seen in STE versus TTE cohort. On multivariate analysis, seroma history was associated with SSI development (OR 3.18, p = 0.041).There was no significant difference in the rate of post-operative SSI following breast reconstruction with STE relative to TTE.

    View details for DOI 10.1016/j.bjps.2022.04.087

    View details for PubMedID 35768293

  • Air versus Saline: The Effect of Tissue Expander Fill on Outcomes of Prepectoral Breast Reconstruction. Plastic and reconstructive surgery Yesantharao, P. S., Rizk, N., Martin, S. A., Tevlin, R., Lee, G. K., Nazerali, R. S. 2022

    Abstract

    BACKGROUND: Traditionally, saline is used for intraoperative/postoperative expansion in two-stage alloplastic breast reconstruction. Recently, intraoperative expansion with air has been proposed, to reduce pressure on the mastectomy skin flap in the immediate postoperative setting. The authors examined whether the intraoperative tissue expansion medium (i.e., air versus saline) affected postmastectomy complications in two-stage prepectoral reconstruction.METHODS: This was a retrospective cohort study of 87 patients (144 breasts) undergoing prepectoral breast reconstruction at the authors' institution. Patient data were abstracted from medical records. Stepwise, multivariable-adjusted logistic regression using robust variances was used to identify predictors of postmastectomy complications. Statistical and power analyses were completed.RESULTS: Of the 87 study patients, 29 (33.3 percent) received intraoperative saline fill and 58 (66.7 percent) received air fill. Demographic/clinical data were well-matched between cohorts. Median follow-up was 165 days, and average patient age was 46.7 years. Initial tissue expander fill volumes were similar between study cohorts (p = 0.2). The crude association between air versus saline fill on overall complication rates suggested that air-filled tissue expanders may be protective (OR = 0.4; p = 0.03), and the suggested protective effect was maintained with borderline significance even after potential confounders (i.e., American Society of Anesthesiologists class III or higher, body mass index, diabetes, mastectomy specimen weight, smoking status) were added to the model (OR = 0.4; p = 0.05). In addition, fewer complications requiring salvage reoperation were observed with air-filled tissue expanders (adjusted OR = 0.3; p = 0.02).CONCLUSIONS: The medium used for immediate intraoperative tissue expansion impacted postmastectomy outcomes in patients undergoing two-stage prepectoral breast reconstruction. The results demonstrated that air-filled tissue expanders were associated with fewer postoperative complications/salvage reoperations relative to saline-filled tissue expanders.CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

    View details for DOI 10.1097/PRS.0000000000009191

    View details for PubMedID 35499585

  • Impact of Incision Placement on Ischemic Complications in Microsurgical Breast Reconstruction. Plastic and reconstructive surgery Tevlin, R., Griffin, M., Karin, M., Wapnir, I., Momeni, A. 1800; 149 (2): 316-322

    Abstract

    BACKGROUND: Nipple-sparing mastectomy is associated with greater patient satisfaction than non-nipple-sparing approaches. Although various nipple-sparing mastectomy incisions have been described, the authors hypothesized that incision location would impact the rate and location of ischemic complications to the mastectomy skin flap.METHODS: A prospectively maintained database was queried to identify patients who underwent nipple-sparing mastectomy with immediate microsurgical reconstruction with a minimum postoperative follow-up of 12 months. The impact of incision location on postoperative ischemic complications was investigated. Major complications were defined as those that required reexploration in the operating room or inpatient management; minor complications were amenable to outpatient management. Multivariable logistic and linear regression were performed to investigate risk factors for postoperative complications following breast reconstruction.RESULTS: Eighty-seven patients met inclusion criteria. The following nipple-sparing mastectomy incisions were used: radial with a periareolar extension (39 percent), inframammary fold (31 percent), vertical with a periareolar extension (22 percent), vertical (6 percent), and radial (2 percent). Seven patients (8 percent) had major complications, whereas twenty-six patients (29.9 percent) developed minor postoperative complications. Inframammary fold incisions were associated with significantly greater rates of mastectomy skin flap necrosis (p = 0.002), whereas periareolar incisions were associated with significantly greater rates of postoperative nipple-areola complex necrosis (p = 0.04).CONCLUSIONS: The authors report a significant association between incision location and ischemic complications to the breast skin envelope in microsurgical breast reconstruction. The authors observed a significant association of inframammary fold and periareolar incisions with mastectomy skin flap and nipple-areola complex necrosis, respectively.CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

    View details for DOI 10.1097/PRS.0000000000008770

    View details for PubMedID 35077404

  • Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity Across Mouse and Human Embryonic Origins Griffin, M., King, M. W., Guardino, N., Tevlin, R., Fahy, E. J., Mascharak, S., Abbas, D., Lavin, C. V., Wan, D., Longaker, M. ELSEVIER SCIENCE INC. 2021: S201-S202
  • The Impact of Reconstructive Modality on the Severity of Postoperative Complications in Breast Reconstruction Pedreira, R., Tevlin, R., Griffin, M., Wan, D., Momeni, A. ELSEVIER SCIENCE INC. 2021: S211-S212
  • Acellular Dermal Matrix Modulation of the Peri-Prosthetic Breast Microenvironment During Breast Reconstruction Tevlin, R., Januszyk, M., Griffin, M., Shefren, K., Chan, C. F., Momeni, A., Wan, D. C., Longaker, M. T. ELSEVIER SCIENCE INC. 2021: S195-S196
  • Denervation During Mandibular Distraction Osteogenesis Results in Impaired Osteogenesis Tevlin, R., Januszyk, M., Griffin, M., Salhotra, A., Wan, D. C., Chan, C. F., Longaker, M. T. ELSEVIER SCIENCE INC. 2021: S196-S197
  • Deferoxamine to minimize fibrosis during radiation therapy. Advances in wound care Tevlin, R., Longaker, M. T., Wan, D. 2021

    Abstract

    Significance By 2030, there will be over 4 million radiation-treated cancer survivors living in the US. Irradiation triggers inflammation, fibroblast activation, and extracellular matrix deposition in addition to reactive oxygen species (ROS) generation, leading to a chronic inflammatory response. Radiation-induced fibrosis (RIF) is a progressive pathology resulting in skin pigmentation, reduced elasticity, ulceration and dermal thickening, cosmetic deformity, pain, and the need for reconstructive surgery. Recent Advances Deferoxamine (DFO) is an FDA-approved iron chelator for blood dyscrasia management, which has been found to be pro-angiogenic, to decrease free radical formation, and reduce cell death. DFO has shown great promise in the treatment and prophylaxis of RIF in preclinical studies. Critical Issues Systemic DFO has a short half-life and is cumbersome to deliver to patients intravenously. Transdermal DFO delivery is complicated by its high atomic mass and hydrophilicity, preventing stratum corneum penetration. A transdermal drug delivery system was developed to address these challenges, in addition to a strategy for topical administration. Future Directions DFO has great potential to translate from bench to bedside. An important step in translation of DFO for RIF prophylaxis is to ensure that DFO treatment does not affect the efficacy of radiation therapy. Furthermore, following an initial plethora of studies reporting DFO treatment by intravenous and subcutaneous routes, a significant advantage of recent studies is the success of transdermal and topical delivery. Given the strong foundation of basic scientific research supporting the use of DFO treatment on RIF, clinicians will be closely following the results of the ongoing human studies.

    View details for DOI 10.1089/wound.2021.0021

    View details for PubMedID 34074152

  • Autologous Fat Grafting and the Occurrence of Radiation-Induced Capsular Contracture. Annals of plastic surgery Martin, S., Cai, L., Beniwal, A., Tevlin, R., Lee, G., Nazerali, R. S. 2021

    Abstract

    INTRODUCTION: Radiation therapy is a known risk factor for capsular contracture formation after implant-based breast reconstruction. Although autologous fat grafting (AFG) has been shown to reverse radiation-induced tissue fibrosis, its use as a prophylactic agent against capsular contraction has not been assessed in the clinical setting. In the setting of 2-stage implant-based reconstruction and postmastectomy radiation therapy, we explored the effect AFG has on the prevalence of capsular contracture.MATERIALS AND METHODS: A retrospective chart review of patients who underwent immediate tissue expander (TE) placement followed by postmastectomy radiation therapy and secondary implant-based reconstruction at our institution between January 2012 and December 2019 was performed. Patients were divided into 2 cohorts based on whether or not AFG was performed at the time of secondary reconstruction. The primary outcome of interest was the occurrence of capsular contracture after TE exchange.RESULTS: Overall 57 patients (57 breasts) were included, 33 of whom received AFG at the time of TE exchange. All but 1 patient underwent submuscular implant placement, and the mean follow-up was 1.96 years. There was no significant difference in the prevalence of medical comorbidities between the study groups.Capsular contracture occurred in 24 patients (42.1%). Seventeen of these patients had undergone AFG at the time of TE exchange (17/33 patients, 51.5%), and 7 of these patients had not (7/24 patients, 29.2%). Most of the capsular contracture cases were Baker grades III or IV (14 patients, 58.3%), and 50% of patients with capsular contracture of any grade ultimately required operative intervention. Multivariate logistic regression analysis demonstrated that AFG did not significantly influence the occurrence or severity of capsular contracture, or did not impact the need for operative intervention in this patient population.CONCLUSIONS: Implant-based reconstruction of the irradiated breast is associated with high postoperative capsular contracture rates. Although AFG has shown promise in reversing radiation-induced dermal fibrosis, no protective effect on the development of capsular contracture after stage 2 reconstruction was observed in this study population. Further investigation in the form of randomized, prospective studies is needed to better assess the utility of AFG in preventing capsular contracture in irradiated patients.

    View details for DOI 10.1097/SAP.0000000000002817

    View details for PubMedID 33833172

  • Skeletal Stem Cells-A Paradigm Shift in the Field of Craniofacial Bone Tissue Engineering. Frontiers in dental medicine Tevlin, R., Longaker, M. T., Wan, D. C. 2020; 1

    Abstract

    Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace "like with like." With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation in vivo can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level in vivo without prior in vitro culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated in situ with broad potential applications in craniofacial tissue engineering.

    View details for DOI 10.3389/fdmed.2020.596706

    View details for PubMedID 35664558

    View details for PubMedCentralID PMC9161996

  • Immediate Targeted Nipple-Areolar Complex Re-Innervation: Improving Outcomes in Immediate Autologous Breast Reconstruction Tevlin, R., Wapnir, I., Nguyen, D. ELSEVIER SCIENCE INC. 2020: S226–S227
  • Air vs Saline: Effect of Tissue Expander Fill Prepectoral Breast Reconstruction Postoperative Complication Rizk, N., Martin, S., Tevlin, R., Lee, G., Nazerali, R. ELSEVIER SCIENCE INC. 2020: E81
  • Neonatal Compartment Syndrome and Compound Presentation at Birth. Journal of hand surgery global online Shen, A. H., Tevlin, R., Kwan, M. D., Ho, O. H., Fox, P. M. 2020; 2 (3): 166-170

    Abstract

    Neonatal compartment syndrome is a rare condition. Early diagnosis and timely surgical intervention are paramount to optimize outcome. Time to fasciotomy is the most important prognostic factor. The purposes of this study were to describe a case presentation of neonatal compartment syndrome associated with a compound birth presentation and to perform a literature review. In this case, the neonate's fingers were noted to be present on maternal cervical examination 24 hours before delivery. The patient then was noted to have a sentinel skin lesion. A diagnosis of neonatal compartment syndrome was suspected, and she underwent urgent fasciotomy. Literature review identified a total of 60 patients from 26 studies. Most patients were managed operatively. All patients presented with a sentinel skin lesion, emphasizing the importance of this clinical sign in diagnosis. Manometry is not routinely performed and no standards are available for acceptable pressure gradients.

    View details for DOI 10.1016/j.jhsg.2020.04.001

    View details for PubMedID 35415493

    View details for PubMedCentralID PMC8991503

  • Should free deep inferior epigastric artery perforator flaps be considered a quality indicator in breast reconstruction? Journal of plastic, reconstructive & aesthetic surgery : JPRAS Tevlin, R., Wan, D. C., Momeni, A. 2019

    Abstract

    Over the past several decades, technical advances in breast reconstruction have resulted in the development of flaps that are aimed at progressively decreasing abdominal wall morbidity. There is, however, ongoing controversy related to the superiority of deep inferior epigastric perforator (DIEP) flaps over muscle-sparing TRAM (MS-TRAM) flaps. Hence, the question remains unanswered as to which approach should be considered the standard of care, and more importantly, whether the rate of DIEP flap utilization should be considered a quality metric in breast reconstruction. In this review article, we examine the literature pertaining to abdominal free tissue transfer in breast reconstruction from both donor site and flap characteristics as well as the resultant complications and morbidity. The impact on the donor site remains a prevailing principle for autologous breast reconstruction; thus, must be adequately respected when classifying what is left behind following flap harvest. The most commonly used nomenclature is too simplistic. This, in turn, leads to inadequate incorporation of critical variables, such as degree of muscular preservation, fascial involvement, mesh implantation, and segmental nerve anatomy. Currently, there is insufficient evidence to support DIEP flap harvest as a quality indicator in breast reconstruction, as DIEP flap outcomes are not clearly superior when compared with MS-TRAM flaps.

    View details for DOI 10.1016/j.bjps.2019.08.005

    View details for PubMedID 31570216

  • Acellular Dermal Matrix Reduces Myofibroblast Presence in the Breast Capsule. Plastic and reconstructive surgery. Global open Tevlin, R., Borrelli, M. R., Irizarry, D., Nguyen, D., Wan, D. C., Momeni, A. 2019; 7 (5): e2213

    Abstract

    Background: Capsular contracture remains a common complication after implant-based breast reconstruction. Previous work has suggested that the use of acellular dermal matrix (ADM) reduces the rate of capsular contracture, though little is understood about the underlying mechanism. As myofibroblasts are believed to be the key cells implicated in contracture formation, we hypothesized that ADM would result in a reduction in periprosthetic myofibroblast concentration.Methods: Five patients who underwent immediate prepectoral tissue expander placement with anterior ADM coverage and an inferior cuff were included. At the second stage, tissue samples were obtained of both ADM and capsule from each reconstructed breast. Samples were then prepared for hematoxylin and eosin staining and immunohistochemistry for myofibroblast identification (alpha smooth muscle actin and vimentin positive and desmin negative) and analysis. Experimental values are presented as mean ± SD unless otherwise stated. Statistical significance was determined using unpaired t test.Results: Successful incorporation of ADM was noted in all cases. A significant reduction in myofibroblast concentration was noted in the ADM versus the capsule (P = 0.0018). This was paralleled by significantly thicker periprosthetic capsule formation overlying the formerly raw pectoralis major muscle, that is, not covered by ADM (P < 0.0001).Conclusions: In the presence of ADM, there are significantly fewer myofibroblasts in breast capsules and thinner capsules on histology. Given the central role of myofibroblasts in the development of clinically significant capsular contracture, this study unmasks a possible mechanism for the protective effect of ADM with respect to capsular contracture development.

    View details for DOI 10.1097/GOX.0000000000002213

    View details for PubMedID 31333946

  • Preoperative Computed Tomography Angiography in Autologous Breast Reconstruction-Incidence and Impact of Incidentalomas PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN Tevlin, R., Borrelli, M. R., Dung Nguyen, Momeni, A. 2018; 6 (12): e2019

    Abstract

    Incidentalomas are lesions found coincidentally during examination, imaging, or surgical procedures. Preoperative computed tomography angiography (CTA) before abdominal flap harvest for breast reconstruction can lead to identification of incidentalomas leading to the need for further investigations. The aim of this study was to examine the prevalence of incidental findings on preoperative CTA and to determine their impact on management.A retrospective chart review was performed at a single tertiary institution. CTA reports were analyzed for the presence of incidental findings and details of follow-up were studied. Logistic regression was used to identify factors associated with incidental findings.One hundred eighteen patients with a mean age of 49 years were included in the study. The majority of patients underwent bilateral reconstruction (65%, n = 77) in the immediate setting (70%, n = 83). Fifty-six percentage had an incidental finding on CTA, with hepatic (20%), renal (14%), and osseous (11%) abnormalities being most common. Additional imaging including ultrasound, CT, and magnetic resonance imaging were recommended in 19 cases (16%). Additional consultations were sought for 3 patients before reconstruction (with suspicion of bone metastases, an intraabdominal mass, and suspicion of colonic malignancy, respectively). No significant surgical delay secondary to CT findings was noted.Incidentalomas following preoperative CTA of the abdomen/pelvis are common (56%). However, unlike previous reports, we did not observe a change in reconstructive plan following incidentaloma discovery. We recommend that all patients are counseled pre-CTA regarding the possibilities of incidentaloma detection and need for additional imaging.

    View details for PubMedID 30656111

  • Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds. Advances in wound care Hu, M. S., Hong, W. X., Januszyk, M., Walmsley, G. G., Luan, A., Maan, Z. N., Moshrefi, S., Tevlin, R., Wan, D. C., Gurtner, G. C., Longaker, M. T., Lorenz, H. P. 2018; 7 (8): 262-275

    Abstract

    Objective: In early gestation, fetal wounds heal without fibrosis in a process resembling regeneration. Elucidating this remarkable mechanism can result in tremendous benefits to prevent scarring. Fetal mouse cutaneous wounds before embryonic day (E)18 heal without scar. Herein, we analyze expression profiles of fetal and postnatal wounds utilizing updated gene annotations and pathway analysis to further delineate between repair and regeneration. Approach: Dorsal wounds from time-dated pregnant BALB/c mouse fetuses and adult mice at various time points were collected. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was utilized to select genes with >2-fold expression differences with a false discovery rate of <2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways. Results: Our analysis identified 471 differentially expressed genes in fetal versus adult wounds following injury. Utilizing enrichment analysis of significant genes, we identified the top 20 signaling pathways that were upregulated and downregulated at 1 and 12 h after injury. At 24 h after injury, we discovered 18 signaling pathways upregulated in adult wounds and 11 pathways upregulated in fetal wounds. Innovation: These novel target genes and pathways may reveal repair mechanisms of the early fetus that promote regeneration over fibrosis. Conclusion: Our microarray analysis recognizes hundreds of possible genes as candidates for regulators of scarless versus scarring wound repair. Enrichment analysis reveals 109 signaling pathways related to fetal scarless wound healing.

    View details for DOI 10.1089/wound.2017.0779

    View details for PubMedID 30087802

    View details for PubMedCentralID PMC6080120

  • Pathway Analysis of Gene Expression in Murine Fetal and Adult Wounds ADVANCES IN WOUND CARE Hu, M. S., Hong, W., Januszyk, M., Walmsley, G. G., Luan, A., Maan, Z. N., Moshrefi, S., Tevlin, R., Wan, D. C., Gurtner, G. C., Longaker, M. T., Lorenz, H. 2018
  • Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts ADVANCES IN WOUND CARE Hu, M. S., Borrelli, M. R., Januszyk, M., Luan, A., Malhotra, S., Walmsley, G. G., Hong, W., Tevlin, R., Gurtner, G. C., Longaker, M. T., Lorenz, H. P. 2018; 7 (1): 1–10

    Abstract

    Objective: Fetuses early in gestation heal skin wounds without forming scars. The biological mechanisms behind this process are largely unknown. Fibroblasts, however, are cells known to be intimately involved in wound healing and scar formation. We examined fibroblasts in different stages of development to characterize differences in gene expression that may result in the switch from regenerative wound repair to repair with scarring. Approach: Fibroblasts were isolated and cultured from the back skin of BALB/c wild-type mouse fetuses at embryonic day (E)14 and E18 (n = 10). The fibroblast total RNA was extracted, and microarray analysis was conducted using chips containing 42,000 genes. Significance analysis of microarrays was performed to identify genes with greater than twofold expression difference and a false discovery rate of less than two. Identified genes subsequently underwent enrichment analysis to detect differentially expressed pathways. Results: Two hundred seventy-five genes were differentially expressed between E14 and E18 in fetal fibroblasts. Thirty genes were significantly downregulated and 245 genes were significantly upregulated at E18 compared with E14. Ingenuity pathway analysis identified the top 20 signaling pathways differentially activated in fetal fibroblasts between the E18 and E14 time points. Innovation: To our knowledge, this work represents the first instance where differentially expressed genes and signaling pathways between fetal fibroblasts at E14 and E18 have been studied. Conclusion: The genes and pathways identified here potentially underlie the mechanism behind the transition from fetal wound healing via regeneration to wound healing by repair, and may prove to be key targets for future therapeutics.

    View details for PubMedID 29344429

  • Shifting Skeletal Stem Cell Dynamics Underlie Skeletal Aging in Mice Marecic, O., McArdle, A., Seo, E., Tevlin, R., Gulati, G. S., Murphy, M. P., Lopez, M., Weissman, I. L., Chan, C. K., Longaker, M. T. ELSEVIER SCIENCE INC. 2017: S166
  • Pharmacological rescue of diabetic skeletal stem cell niches SCIENCE TRANSLATIONAL MEDICINE Tevlin, R., Seo, E., Marecic, O., McArdle, A., Tong, X., Zimdahl, B., Malkovskiy, A., Sinha, R., Gulati, G., Li, X., Wearda, T., Morganti, R., Lopez, M., Ransom, R. C., Duldulao, C. R., Rodrigues, M., Nguyen, A., Januszyk, M., Maan, Z., Paik, K., Yapa, K., Rajadas, J., Wan, D. C., Gurtner, G. C., Snyder, M., Beachy, P. A., Yang, F., Goodman, S. B., Weissman, I. L., Chan, C. F., Longaker, M. T. 2017; 9 (372)
  • Human Adipose-Derived Stromal Cell Isolation Methods and Use in Osteogenic and Adipogenic In Vivo Applications. Current protocols in stem cell biology Brett, E., Tevlin, R., McArdle, A., Seo, E. Y., Chan, C. K., Wan, D. C., Longaker, M. T. 2017; 43

    Abstract

    Adipose tissue represents an abundant and easily accessible source of multipotent cells, which may serve as excellent building blocks for tissue engineering. This article presents a newly described protocol for isolating adipose-derived stromal cells (ASCs) from human lipoaspirate, compared to the standard protocol for harvesting ASCs established in 2001. Human ASC isolation is performed using two methods, and resultant cells are compared through cell yield, cell viability, cell proliferation and regenerative potential. The osteogenic and adipogenic potential of ASCs isolated using both protocols are assessed invitro and gene expression analysis is performed. The focus of this series of protocols is the regenerative potential of both cell populations in vivo. As such, the two in vivo animal models described are fat graft retention (soft tissue reconstruction) and calvarial defect healing (bone regeneration). The techniques described comprise fat grafting with cell assisted lipotransfer, and calvarial defect creation healed with cell-seeded scaffolds. © 2017 by John Wiley & Sons, Inc.

    View details for PubMedID 29140567

  • A Novel Method of Human Adipose-Derived Stem Cell Isolation with Resultant Increased Cell Yield PLASTIC AND RECONSTRUCTIVE SURGERY Tevlin, R., McArdle, A., Brett, E., Chung, M. T., Paik, K., Seo, E. Y., Walmsley, G. G., Duldulao, C. R., Atashroo, D., Zielins, E., Vistnes, S., Chan, C. K., Wan, D. C., Longaker, M. T. 2016; 138 (6): 983E-996E

    Abstract

    The authors have developed a novel protocol for isolating adipose-derived stem cells from human lipoaspirate. In this study, they compare their new method to a previously published standard protocol.Human adipose-derived stem cell isolation was performed using two methods to compare cell yield, cell viability, cell proliferation, and regenerative potential. The new and conventional isolation methods differ in two key areas: the collagenase digestion buffer constituents and the use of an orbital shaker. The osteogenic and adipogenic potential of adipose-derived stem cells isolated using both protocols was assessed in vitro, and gene expression analysis was performed. To assess the ability of the isolated cells to generate bone in vivo, the authors created critical-size calvarial defects in mice, which were treated with adipose-derived stem cells loaded onto hydroxyapatite-coated poly(lactic-co-glycolic acid) scaffolds. To test the ability of the isolated cells to enhance adipogenesis, the cells were added to lipoaspirate and placed beneath the scalp of immunocompromised mice. Fat graft volume retention was subsequently assessed by serial computed tomographic volumetric scanning.The new method resulted in a 10-fold increased yield of adipose-derived stem cells compared with the conventional method. Cells harvested using the new method demonstrated significantly increased cell viability and proliferation in vitro (p < 0.05). New method cells also demonstrated significantly enhanced osteogenic and adipogenic differentiation capacity in vitro (p < 0.05) in comparison with the conventional method cells. Both cell groups demonstrated equivalent osteogenic and adipogenic regenerative potential in mice.The authors have developed a protocol that maximizes the yield of adipose-derived stem cells derived from lipoaspirate. The new method cells have increased osteogenic and adipogenic potential in vitro and are not inferior to conventional method cells in terms of their ability to generate bone and fat in vivo.Therapeutic, V.

    View details for DOI 10.1097/PRS.0000000000002790

    View details for PubMedID 27537222

  • Stem and progenitor cells: advancing bone tissue engineering. Drug delivery and translational research Tevlin, R., Walmsley, G. G., Marecic, O., Hu, M. S., Wan, D. C., Longaker, M. T. 2016; 6 (2): 159-173

    Abstract

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone-the best option-is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

    View details for DOI 10.1007/s13346-015-0235-1

    View details for PubMedID 25990836

    View details for PubMedCentralID PMC4654714

  • Murine Dermal Fibroblast Isolation by FACS. Journal of visualized experiments : JoVE Walmsley, G. G., Maan, Z. N., Hu, M. S., Atashroo, D. A., Whittam, A. J., Duscher, D., Tevlin, R., Marecic, O., Lorenz, H. P., Gurtner, G. C., Longaker, M. T. 2016

    Abstract

    Fibroblasts are the principle cell type responsible for secreting extracellular matrix and are a critical component of many organs and tissues. Fibroblast physiology and pathology underlie a spectrum of clinical entities, including fibroses in multiple organs, hypertrophic scarring following burns, loss of cardiac function following ischemia, and the formation of cancer stroma. However, fibroblasts remain a poorly characterized type of cell, largely due to their inherent heterogeneity. Existing methods for the isolation of fibroblasts require time in cell culture that profoundly influences cell phenotype and behavior. Consequently, many studies investigating fibroblast biology rely upon in vitro manipulation and do not accurately capture fibroblast behavior in vivo. To overcome this problem, we developed a FACS-based protocol for the isolation of fibroblasts from the dorsal skin of adult mice that does not require cell culture, thereby preserving the physiologic transcriptional and proteomic profile of each cell. Our strategy allows for exclusion of non-mesenchymal lineages via a lineage negative gate (Lin(-)) rather than a positive selection strategy to avoid pre-selection or enrichment of a subpopulation of fibroblasts expressing specific surface markers and be as inclusive as possible across this heterogeneous cell type.

    View details for DOI 10.3791/53430

    View details for PubMedID 26780559

    View details for PubMedCentralID PMC4781205

  • Murine Dermal Fibroblast Isolation by FACS JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Walmsley, G. G., Maan, Z. N., Hu, M. S., Atashroo, D. A., Whittam, A. J., Duscher, D., Tevlin, R., Marecic, O., Lorenz, H. P., Gurtner, G. C., Longaker, M. T. 2016

    Abstract

    Fibroblasts are the principle cell type responsible for secreting extracellular matrix and are a critical component of many organs and tissues. Fibroblast physiology and pathology underlie a spectrum of clinical entities, including fibroses in multiple organs, hypertrophic scarring following burns, loss of cardiac function following ischemia, and the formation of cancer stroma. However, fibroblasts remain a poorly characterized type of cell, largely due to their inherent heterogeneity. Existing methods for the isolation of fibroblasts require time in cell culture that profoundly influences cell phenotype and behavior. Consequently, many studies investigating fibroblast biology rely upon in vitro manipulation and do not accurately capture fibroblast behavior in vivo. To overcome this problem, we developed a FACS-based protocol for the isolation of fibroblasts from the dorsal skin of adult mice that does not require cell culture, thereby preserving the physiologic transcriptional and proteomic profile of each cell. Our strategy allows for exclusion of non-mesenchymal lineages via a lineage negative gate (Lin(-)) rather than a positive selection strategy to avoid pre-selection or enrichment of a subpopulation of fibroblasts expressing specific surface markers and be as inclusive as possible across this heterogeneous cell type.

    View details for DOI 10.3791/53430

    View details for Web of Science ID 000368577400023

    View details for PubMedCentralID PMC4781205

  • Delivery of Macrophages in a Biomimetic Scaffold Accelerates Diabetic Wound Healing Through Enhanced Angiogenesis Walmsley, G. G., Hu, M. S., Duscher, D., Januszyk, M., Maan, Z. N., Senarath-Yapa, K., Tevlin, R., Zielins, E. R., Gurtner, G. C., Longaker, M. T. ELSEVIER SCIENCE INC. 2015: S113–S114
  • Impairment in Fracture Healing in a Mouse Model of Type 2 Diabetes Is Driven by Skeletal Stem Cell Niche Dysregulation Tevlin, R., Seo, E., Mc Ardle, A., Tong, X., Januszyk, M., Yang, F., Gurtner, G. C., Chan, C. F., Weissman, I. L., Longaker, M. T. ELSEVIER SCIENCE INC. 2015: S115
  • High-Throughput Screening of Surface Marker Expression on Undifferentiated and Differentiated Human Adipose-Derived Stromal Cells TISSUE ENGINEERING PART A Walmsley, G. G., Atashroo, D. A., Maan, Z. N., Hu, M. S., Zielins, E. R., Tsai, J. M., Duscher, D., Paik, K., Tevlin, R., Marecic, O., Wan, D. C., Gurtner, G. C., Longaker, M. T. 2015; 21 (15-16): 2281-2291

    Abstract

    Adipose tissue contains an abundant source of multipotent mesenchymal cells termed "adipose-derived stromal cells" (ASCs) that hold potential for regenerative medicine. However, the heterogeneity inherent to ASCs harvested using standard methodologies remains largely undefined, particularly in regards to differences across donors. Identifying the subpopulations of ASCs predisposed toward differentiation along distinct lineages holds value for improving graft survival, predictability, and efficiency. Human ASCs (hASCs) from three different donors were independently isolated by density-based centrifugation from adipose tissue and maintained in culture or differentiated along either adipogenic or osteogenic lineages using differentiation media. Undifferentiated and differentiated hASCs were then analyzed for the presence of 242 human surface markers by flow cytometry analysis. By comprehensively characterizing the surface marker profile of undifferentiated hASCs using flow cytometry, we gained novel insights into the heterogeneity underlying protein expression on the surface of cultured undifferentiated hASCs across different donors. Comparison of the surface marker profile of undifferentiated hASCs with hASCs that have undergone osteogenic or adipogenic differentiation allowed for the identification of surface markers that were upregulated and downregulated by osteogenic or adipogenic differentiation. Osteogenic differentiation induced upregulation of CD164 and downregulation of CD49a, CD49b, CD49c, CD49d, CD55, CD58, CD105, and CD166 while adipogenic differentiation induced upregulation of CD36, CD40, CD146, CD164, and CD271 and downregulation of CD49b, CD49c, CD49d, CD71, CD105, and CD166. These results lend support to the notion that hASCs isolated using standard methodologies represent a heterogeneous population and serve as a foundation for future studies seeking to maximize their regenerative potential through fluorescence-activated cell sorting-based selection before therapy.

    View details for DOI 10.1089/ten.tea.2015.0039

    View details for Web of Science ID 000359812700014

    View details for PubMedID 26020286

    View details for PubMedCentralID PMC4529076

  • Nanotechnology in bone tissue engineering NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE Walmsley, G. G., McArdle, A., Tevlin, R., Momeni, A., Atashroo, D., Hu, M. S., Feroze, A. H., Wong, V. W., Lorenz, P. H., Longaker, M. T., Wan, D. C. 2015; 11 (5): 1253-1263

    Abstract

    Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases.Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field.

    View details for DOI 10.1016/j.nano.2015.02.013

    View details for Web of Science ID 000363967100022

    View details for PubMedID 25791811

    View details for PubMedCentralID PMC4476906

  • Scarless wound healing: chasing the holy grail. Plastic and reconstructive surgery Walmsley, G. G., Maan, Z. N., Wong, V. W., Duscher, D., Hu, M. S., Zielins, E. R., Wearda, T., Muhonen, E., McArdle, A., Tevlin, R., Atashroo, D. A., Senarath-Yapa, K., Lorenz, H. P., Gurtner, G. C., Longaker, M. T. 2015; 135 (3): 907-917

    Abstract

    Over 100 million patients acquire scars in the industrialized world each year, primarily as a result of elective operations. Although undefined, the global incidence of scarring is even larger, extending to significant numbers of burn and other trauma-related wounds. Scars have the potential to exert a profound psychological and physical impact on the individual. Beyond aesthetic considerations and potential disfigurement, scarring can result in restriction of movement and reduced quality of life. The formation of a scar following skin injury is a consequence of wound healing occurring through reparative rather than regenerative mechanisms. In this article, the authors review the basic stages of wound healing; differences between adult and fetal wound healing; various mechanical, genetic, and pharmacologic strategies to reduce scarring; and the biology of skin stem/progenitor cells that may hold the key to scarless regeneration.

    View details for DOI 10.1097/PRS.0000000000000972

    View details for PubMedID 25719706

  • The role and regulation of osteoclasts in normal bone homeostasis and in response to injury. Plastic and reconstructive surgery McArdle, A., Marecic, O., Tevlin, R., Walmsley, G. G., Chan, C. K., Longaker, M. T., Wan, D. C. 2015; 135 (3): 808-816

    Abstract

    Bone is a dynamic tissue, with a range of diverse functions, including locomotion, protection of internal organs, and hematopoiesis. Optimum treatment of fractures and/or bone defects requires knowledge of the complex cellular interactions involved with bone healing and remodeling. Emerging data have underscored the importance of osteoclasts in this process, playing a key role both in normal bone turnover and in facilitating bone regeneration. In this review, the authors discuss the basic principles of osteoclast biology, including its cellular origins, its function, and key regulatory mechanisms, in addition to conditions that arise when osteoclast function is altered.

    View details for DOI 10.1097/PRS.0000000000000963

    View details for PubMedID 25719699

  • Impact of surgical innovation on tissue repair in the surgical patient. British journal of surgery Tevlin, R., Atashroo, D., Duscher, D., Mc Ardle, A., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2015; 102 (2): e41-55

    Abstract

    Throughout history, surgeons have been prolific innovators, which is hardly surprising as most surgeons innovate daily, tailoring their intervention to the intrinsic uniqueness of each operation, each patient and each disease. Innovation can be defined as the application of better solutions that meet new requirements, unarticulated needs or existing market needs. In the past two decades, surgical innovation has significantly improved patient outcomes, complication rates and length of hospital stay. There is one key area that has great potential to change the face of surgical practice and which is still in its infancy: the realm of regenerative medicine and tissue engineering.A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key surgical innovations influencing regenerative medicine, with a focus on osseous, cutaneous and soft tissue reconstruction.This review describes recent advances in regenerative medicine, documenting key innovations in osseous, cutaneous and soft tissue regeneration that have brought regenerative medicine to the forefront of the surgical imagination.Surgical innovation in the emerging field of regenerative medicine has the ability to make a major impact on surgery on a daily basis.

    View details for DOI 10.1002/bjs.9672

    View details for PubMedID 25627135

  • Assessment of viability of human fat injection into nude mice with micro-computed tomography. Journal of visualized experiments : JoVE Atashroo, D. A., Paik, K. J., Chung, M. T., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C. R., Walmsley, G. G., Wearda, T., Marecic, O., Longaker, M. T., Wan, D. C. 2015

    View details for DOI 10.3791/52217

    View details for PubMedID 25590561

  • Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis. Journal of visualized experiments : JoVE Zielins, E. R., Tevlin, R., Hu, M. S., Chung, M. T., McArdle, A., Paik, K. J., Atashroo, D., Duldulao, C. R., Luan, A., Senarath-Yapa, K., Walmsley, G. G., Wearda, T., Longaker, M. T., Wan, D. C. 2015

    View details for DOI 10.3791/52181

    View details for PubMedID 25650785

  • Impact of surgical innovation on tissue repair in the surgical patient. British journal of surgery Tevlin, R., Atashroo, D., Duscher, D., Mc Ardle, A., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2015; 102 (2): e41-55

    View details for DOI 10.1002/bjs.9672

    View details for PubMedID 25627135

  • Isolation and enrichment of human adipose-derived stromal cells for enhanced osteogenesis. Journal of visualized experiments : JoVE Zielins, E. R., Tevlin, R., Hu, M. S., Chung, M. T., McArdle, A., Paik, K. J., Atashroo, D., Duldulao, C. R., Luan, A., Senarath-Yapa, K., Walmsley, G. G., Wearda, T., Longaker, M. T., Wan, D. C. 2015: 52181-?

    Abstract

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are considered the gold standard for stem cell-based tissue engineering applications. However, the process by which they must be harvested can be associated with significant donor site morbidity. In contrast, adipose-derived stromal cells (ASCs) are more readily abundant and more easily harvested, making them an appealing alternative to BM-MSCs. Like BM-MSCs, ASCs can differentiate into osteogenic lineage cells and can be used in tissue engineering applications, such as seeding onto scaffolds for use in craniofacial skeletal defects. ASCs are obtained from the stromal vascular fraction (SVF) of digested adipose tissue, which is a heterogeneous mixture of ASCs, vascular endothelial and mural cells, smooth muscle cells, pericytes, fibroblasts, and circulating cells. Flow cytometric analysis has shown that the surface marker profile for ASCs is similar to that for BM-MSCs. Despite several published reports establishing markers for the ASC phenotype, there is still a lack of consensus over profiles identifying osteoprogenitor cells in this heterogeneous population. This protocol describes how to isolate and use a subpopulation of ASCs with enhanced osteogenic capacity to repair critical-sized calvarial defects.

    View details for DOI 10.3791/52181

    View details for PubMedID 25650785

  • Assessment of viability of human fat injection into nude mice with micro-computed tomography. Journal of visualized experiments : JoVE Atashroo, D. A., Paik, K. J., Chung, M. T., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C. R., Walmsley, G. G., Wearda, T., Marecic, O., Longaker, M. T., Wan, D. C. 2015

    Abstract

    Lipotransfer is a vital tool in the surgeon's armamentarium for the treatment of soft tissue deficits of throughout the body. Fat is the ideal soft tissue filler as it is readily available, easily obtained, inexpensive, and inherently biocompatible.(1) However, despite its burgeoning popularity, fat grafting is hampered by unpredictable results and variable graft survival, with published retention rates ranging anywhere from 10-80%. (1-3) To facilitate investigations on fat grafting, we have therefore developed an animal model that allows for real-time analysis of injected fat volume retention. Briefly, a small cut is made in the scalp of a CD-1 nude mouse and 200-400 µl of processed lipoaspirate is placed over the skull. The scalp is chosen as the recipient site because of its absence of native subcutaneous fat, and because of the excellent background contrast provided by the calvarium, which aids in the analysis process. Micro-computed tomography (micro-CT) is used to scan the graft at baseline and every two weeks thereafter. The CT images are reconstructed, and an imaging software is used to quantify graft volumes. Traditionally, techniques to assess fat graft volume have necessitated euthanizing the study animal to provide just a single assessment of graft weight and volume by physical measurement ex vivo. Biochemical and histological comparisons have likewise required the study animal to be euthanized. This described imaging technique offers the advantage of visualizing and objectively quantifying volume at multiple time points after initial grafting without having to sacrifice the study animal. The technique is limited by the size of the graft able to be injected as larger grafts risk skin and fat necrosis. This method has utility for all studies evaluating fat graft viability and volume retention. It is particularly well-suited to providing a visual representation of fat grafts and following changes in volume over time.

    View details for DOI 10.3791/52217

    View details for PubMedID 25590561

  • Biomaterials for Craniofacial Bone Engineering JOURNAL OF DENTAL RESEARCH Tevlin, R., Mcardle, A., Atashroo, D., Walmsley, G. G., Senarath-Yapa, K., Zielins, E. R., Paik, K. J., Longaker, M. T., Wan, D. C. 2014; 93 (12): 1187-1195
  • The Optimal Fat Graft: Evaluating the Biomechanical Effects of Diameter, Length, and Flow Rate during Fat Placement Atashroo, D., Wearda, T., Raphel, J., Paik, K., Zielins, E. R., Walmsley, G. G., Tevlin, R., Wan, D. C., Heilshorn, S., Longaker, M. T. ELSEVIER SCIENCE INC. 2014: S90
  • Impaired Angiogenesis: A Critical Contributor to Problematic Fracture Healing in Diabetes Tevlin, R., Mc Ardle, A., Senarath-Yapa, K., Rodrigues, M., Maan, Z. N., Li, S., Chan, C. K., Brunski, J., Gurtner, G. C. ELSEVIER SCIENCE INC. 2014: S83
  • Diminished Recruitment of Resident Skeletal Progenitor Cells in Diabetic Fracture Healing Tevlin, R., Seo, E., McArdle, A., Marecic, O., Wearda, T., Senarath-Yapa, K., Zielins, E. R., Chan, C. K., Weissman, I. L., Longaker, M. T. ELSEVIER SCIENCE INC. 2014: S82
  • Heterochronic Parabiosis Rejuvenates Aged Bones McArdle, A., Tevlin, R., Marecic, O., Wearda, T., Senarath-Yapa, K., Walmsley, G. G., Snyder, M. P., Weissman, I. L., Chan, C. K., Longaker, M. T. ELSEVIER SCIENCE INC. 2014: S82–S83
  • Response of Skeletal Progenitor Cells to Fracture Injury in a Mouse Model Marecic, O., McArdle, A., Seo, E., Tevlin, R., Duldulao, C., Wearda, T., Chan, C., Weissman, I. L., Longaker, M. T. ELSEVIER SCIENCE INC. 2014: S86
  • The role of stem cells in aesthetic surgery: fact or fiction? Plastic and reconstructive surgery McArdle, A., Senarath-Yapa, K., Walmsley, G. G., Hu, M., Atashroo, D. A., Tevlin, R., Zielins, E., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (2): 193-200

    Abstract

    Stem cells are attractive candidates for the development of novel therapies, targeting indications that involve functional restoration of defective tissue. Although most stem cell therapies are new and highly experimental, there are clinics around the world that exploit vulnerable patients with the hope of offering supposed stem cell therapies, many of which operate without credible scientific merit, oversight, or other patient protection.We review the potential, as well as drawbacks, for incorporation of stem cells in cosmetic procedures. A review of FDA-approved indications and ongoing clinical trials with adipose stem cells is provided. Furthermore, a "snapshot" analysis of websites using the search terms "stem cell therapy" or "stem cell treatment" or "stem cell facelift" was performed.Despite the protective net cast by regulatory agencies such as the FDA and professional societies such as the American Society of Plastic Surgeons, we are witnessing worrying advertisements for procedures such as stem cell facelifts, stem cell breast augmentations, and even stem cell vaginal rejuvenation. The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence in the majority of cases.Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk. With plastic surgeons at the forefront of stem cell-based regenerative medicine, it is critically important that we provide an example of a rigorous approach to research, data collection, and advertising of stem cell therapies.

    View details for DOI 10.1097/PRS.0000000000000404

    View details for PubMedID 24732654

  • Studies in fat grafting: Part I. Effects of injection technique on in vitro fat viability and in vivo volume retention. Plastic and reconstructive surgery Chung, M. T., Paik, K. J., Atashroo, D. A., Hyun, J. S., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Hu, M. S., Walmsley, G. G., Parisi-Amon, A., Momeni, A., Rimsa, J. R., Commons, G. W., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (1): 29-38

    Abstract

    Fat grafting has become increasingly popular for the correction of soft tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, we compare the biologic properties of fat following injection using two methods.Lipoaspiration samples were obtained from five female donors and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over twelve weeks following injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically.Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at 4, 6, 8, and 12 week time points. This corresponded with significantly greater histological scores for healthy fat and lower scores for injury following injection with the device.Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and our in vitro and in vivo data both support the use of the automated, low shear devices compared to the modified Coleman technique.

    View details for DOI 10.1097/PRS.0000000000000290

    View details for PubMedID 24622574

  • Studies in Fat Grafting: Part II. Effects of Injection Mechanics on Material Properties of Fat PLASTIC AND RECONSTRUCTIVE SURGERY Atashroo, D., Raphel, J., Chung, M. T., Paik, K. J., Parisi-Amon, A., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Walmsley, G. G., Hu, M. S., Momeni, A., Domecus, B., Rimsa, J. R., Greenberg, L., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2014; 134 (1): 39-46

    Abstract

    Although fat grafting can address many soft-tissue deficits, results remain inconsistent. In this study, the authors compared physical properties of fat following injection using an automated, low-shear device or the modified Coleman technique.Lipoaspirate was obtained from nine patients and processed for injection using either a modified Coleman technique or an automated, low-shear device. Fat was passed through a 2-mm cannula and compared with minimally processed fat. A rheometer was used to measure the storage modulus and shear rate at which tissues began to lose their solid-like properties. Viscosity was also measured, and gross properties of treatment groups were evaluated qualitatively with a glass slide test.Fat injected through an automated, low-shear device closely matched physical properties of minimally processed fat. The storage modulus (G') of fat for the device group was greater than for the modified Coleman group, and the onset of breakdown was delayed. Similarly, viscosity measurement of fat from the automated device closely matched minimally processed fat and was greater than that of othe modified Coleman group.The physical properties of lipoaspirate processed using an automated, low-shear device with a 2-mm cannula preserved the intactness of fat more than the modified Coleman technique. The authors' rheologic data demonstrate less damage using an automated device compared with the modified Coleman technique and potentially support its use for improved fat graft integrity.

    View details for DOI 10.1097/PRS.0000000000000289

    View details for Web of Science ID 000338116400043

    View details for PubMedCentralID PMC4101917

  • Studies in fat grafting: Part II. Effects of injection mechanics on material properties of fat. Plastic and reconstructive surgery Atashroo, D., Raphel, J., Chung, M. T., Paik, K. J., Parisi-Amon, A., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Walmsley, G. G., Hu, M. S., Momeni, A., Domecus, B., Rimsa, J. R., Greenberg, L., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2014; 134 (1): 39-46

    Abstract

    Although fat grafting can address many soft-tissue deficits, results remain inconsistent. In this study, the authors compared physical properties of fat following injection using an automated, low-shear device or the modified Coleman technique.Lipoaspirate was obtained from nine patients and processed for injection using either a modified Coleman technique or an automated, low-shear device. Fat was passed through a 2-mm cannula and compared with minimally processed fat. A rheometer was used to measure the storage modulus and shear rate at which tissues began to lose their solid-like properties. Viscosity was also measured, and gross properties of treatment groups were evaluated qualitatively with a glass slide test.Fat injected through an automated, low-shear device closely matched physical properties of minimally processed fat. The storage modulus (G') of fat for the device group was greater than for the modified Coleman group, and the onset of breakdown was delayed. Similarly, viscosity measurement of fat from the automated device closely matched minimally processed fat and was greater than that of othe modified Coleman group.The physical properties of lipoaspirate processed using an automated, low-shear device with a 2-mm cannula preserved the intactness of fat more than the modified Coleman technique. The authors' rheologic data demonstrate less damage using an automated device compared with the modified Coleman technique and potentially support its use for improved fat graft integrity.

    View details for DOI 10.1097/PRS.0000000000000289

    View details for PubMedID 25028817

  • Studies in Fat Grafting: Part I. Effects of Injection Technique on In Vitro Fat Viability and In Vivo Volume Retention PLASTIC AND RECONSTRUCTIVE SURGERY Chung, M. T., Paik, K. J., Atashroo, D. A., Hyun, J. S., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Hu, M. S., Walmsley, G. G., Parisi-Amon, A., Momeni, A., Rimsa, J. R., Commons, G. W., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (1): 29-38

    Abstract

    Fat grafting has become increasingly popular for the correction of soft tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, we compare the biologic properties of fat following injection using two methods.Lipoaspiration samples were obtained from five female donors and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over twelve weeks following injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically.Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at 4, 6, 8, and 12 week time points. This corresponded with significantly greater histological scores for healthy fat and lower scores for injury following injection with the device.Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and our in vitro and in vivo data both support the use of the automated, low shear devices compared to the modified Coleman technique.

    View details for DOI 10.1097/PRS.0000000000000290

    View details for Web of Science ID 000338116400042

  • Abstract 151: short hairpin RNA interference therapy for diabetic murine wound closure and hindlimb ischemia. Plastic and reconstructive surgery Paik, K. J., Rennert, R., Chung, M. T., Sorkin, M., Duscher, D., Atashroo, D., Chen, H., Morrison, S. D., Zimmermann, A., Nauta, A., Ko, S., Tevlin, R., Zielins, E., Hu, M. S., McArdle, A., Walmsley, G., Senarath-Yapa, K., Hong, W. X., Garza, R. M., Duldulao, C., Wearda, T., Momeni, A., Wu, J. C., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2014; 133 (3): 167-168

    View details for DOI 10.1097/01.prs.0000444979.14443.08

    View details for PubMedID 25942261

  • Abstract 165: Enhanced Adipose-Derived Stromal Cell Osteogenesis through Surface Marker Enrichment and BMP Modulation using Magnet-assisted Transfection. Plastic and reconstructive surgery Chung, M. T., Morrison, S. D., Paik, K. J., McArdle, A., Walmsley, G., Senarath-Yapa, K., Hu, M. S., Tevlin, R., Zielins, E., Atashroo, D., Hong, W. X., Duldulao, C., Wearda, T., Garza, R. M., Momeni, A., Longaker, M. T., Wan, D. C. 2014; 133 (3): 181-182

    View details for DOI 10.1097/01.prs.0000444994.28797.34

    View details for PubMedID 25942275

  • Abstract 161: identification of cell-intrinsic mechanisms and differentially regulated genetic pathways responsible for the age-related functional decline in aged skeletal stem cells. Plastic and reconstructive surgery McArdle, A., Chan, C., Seita, J., Senarath-Yapa, K., Hu, M., Walmsley, G. G., Zielins, E., Atashroo, D., Tevlin, R., Weissman, I., Longaker, M. T. 2014; 133 (3): 178-?

    View details for DOI 10.1097/01.prs.0000444990.75431.f1

    View details for PubMedID 25942271

  • Wound healing: an update REGENERATIVE MEDICINE Zielins, E. R., Atashroo, D. A., Maan, Z. N., Duscher, D., Walmsley, G. G., Marecic, O., Hu, M., Senarath-Yapa, K., McArdle, A., Tevlin, R., Wearda, T., Paik, K. J., Duldulao, C., Hong, W. X., Gurtner, G. C., Longaker, M. T. 2014; 9 (6): 817-830

    Abstract

    Wounds, both chronic and acute, continue to be a tremendous socioeconomic burden. As such, technologies drawn from many disciplines within science and engineering are constantly being incorporated into innovative wound healing therapies. While many of these therapies are experimental, they have resulted in new insights into the pathophysiology of wound healing, and in turn the development of more specialized treatments for both normal and abnormal wound healing states. Herein, we review some of the emerging technologies that are currently being developed to aid and improve wound healing after cutaneous injury.

    View details for DOI 10.2217/RME.14.54

    View details for Web of Science ID 000345620600012

  • Osteoclast derivation from mouse bone marrow. Journal of visualized experiments : JoVE Tevlin, R., McArdle, A., Chan, C. K., Pluvinage, J., Walmsley, G. G., Wearda, T., Marecic, O., Hu, M. S., Paik, K. J., Senarath-Yapa, K., Atashroo, D. A., Zielins, E. R., Wan, D. C., Weissman, I. L., Longaker, M. T. 2014

    Abstract

    Osteoclasts are highly specialized cells that are derived from the monocyte/macrophage lineage of the bone marrow. Their unique ability to resorb both the organic and inorganic matrices of bone means that they play a key role in regulating skeletal remodeling. Together, osteoblasts and osteoclasts are responsible for the dynamic coupling process that involves both bone resorption and bone formation acting together to maintain the normal skeleton during health and disease. As the principal bone-resorbing cell in the body, changes in osteoclast differentiation or function can result in profound effects in the body. Diseases associated with altered osteoclast function can range in severity from lethal neonatal disease due to failure to form a marrow space for hematopoiesis, to more commonly observed pathologies such as osteoporosis, in which excessive osteoclastic bone resorption predisposes to fracture formation. An ability to isolate osteoclasts in high numbers in vitro has allowed for significant advances in the understanding of the bone remodeling cycle and has paved the way for the discovery of novel therapeutic strategies that combat these diseases. Here, we describe a protocol to isolate and cultivate osteoclasts from mouse bone marrow that will yield large numbers of osteoclasts.

    View details for DOI 10.3791/52056

    View details for PubMedID 25407120

  • Osteoclast derivation from mouse bone marrow. Journal of visualized experiments : JoVE Tevlin, R., McArdle, A., Chan, C. K., Pluvinage, J., Walmsley, G. G., Wearda, T., Marecic, O., Hu, M. S., Paik, K. J., Senarath-Yapa, K., Atashroo, D. A., Zielins, E. R., Wan, D. C., Weissman, I. L., Longaker, M. T. 2014

    View details for DOI 10.3791/52056

    View details for PubMedID 25407120

  • Wound healing: an update. Regenerative medicine Zielins, E. R., Atashroo, D. A., Maan, Z. N., Duscher, D., Walmsley, G. G., Hu, M., Senarath-Yapa, K., McArdle, A., Tevlin, R., Wearda, T., Paik, K. J., Duldulao, C., Hong, W. X., Gurtner, G. C., Longaker, M. T. 2014; 9 (6): 817-830

    Abstract

    Wounds, both chronic and acute, continue to be a tremendous socioeconomic burden. As such, technologies drawn from many disciplines within science and engineering are constantly being incorporated into innovative wound healing therapies. While many of these therapies are experimental, they have resulted in new insights into the pathophysiology of wound healing, and in turn the development of more specialized treatments for both normal and abnormal wound healing states. Herein, we review some of the emerging technologies that are currently being developed to aid and improve wound healing after cutaneous injury.

    View details for DOI 10.2217/rme.14.54

    View details for PubMedID 25431917