Musculoskeletal Transplant Foundation

Human decellularized adipose matrix (hDAM) has emerged as a promising, off-the-shelf option for soft tissue augmentation, providing a biocompatible scaffold that supports angiogenesis, adipogenesis, and volume retention with minimal immunogenicity. This systematic review synthesizes preclinical and clinical evidence on hDAM's regenerative potential, focusing on its capacity to integrate with host tissue and enhance volume retention. A comprehensive literature search was performed across multiple databases yielding 21 studies (14 preclinical, 6 clinical, and 1 combined) that met eligibility criteria. Risk of bias (RoB) was evaluated for animal and human studies using the Collaboration for the Assessment of Risks and Benefits of Anticancer Therapies (CAMARADES) and RoB In Nonrandomized Studies of Interventions (ROBINS-I) tools, respectively. Key preclinical findings indicate that hDAM supports progressive angiogenesis and adipogenesis, with significant weekly increases in vessel formation and adipocyte development. Linear mixed models were used to quantify these rates, showing an increase of 0.366% per week (p < 0.001) in the percentage of CD31+ positive area, and a 3.88% rise in perilipin-positive area per week (p < 0.001), representing angiogenesis and adipogenesis, respectively. Variability in regeneration rates underscores the influence of different hDAM preparation methods, such as enzyme-free decellularization and ultrasonication, which have been shown to improve cell compatibility and volume retention. Clinical studies demonstrate that hDAM achieves notable volume retention and patient satisfaction, particularly in facial and body contouring applications, while also improving skin texture, tone, and functionality. Compared with traditional autologous fat transfer and synthetic fillers, hDAM offers advantages in integration, resorption rates, and low complication risks, without donor site morbidity. Limitations of current studies include variability in hDAM preparation techniques, inconsistent outcome measures, and a paucity of long-term follow-up data. This review establishes hDAM as a safe and effective scaffold for soft tissue regeneration and provides a quantitative analysis of its regenerative timeline. Standardizing preparation methods and outcome measures, coupled with more randomized clinical trials, will be essential for optimizing treatment protocols. Future directions include exploring patient-specific factors and combination therapies to enhance hDAM's applicability in reconstructive and aesthetic surgery.

Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. Level IV study.

Given the possibility for disease transmission, this study was performed to determine whether there is detectable SARS-CoV-2 viral RNA in the blood of deceased tissue donors. A retrospective analysis of blood samples from eligible deceased tissue donors from Oct 2019 through June 2020 was performed. Plasma aliquots were initially tested with a SARS-CoV-2 NAT Assay; positive samples were further tested using an alternate NAT and an antibody assay. The proportion of donors with confirmed RNAemia and 95% confidence intervals were computed. Of donor samples collected in 2019, 894 yielded valid results, with 6 initially positive, none of which confirmed positive by alternate NAT. Of donor samples collected in 2020, 2562 yielded valid initial NAT results, with 21 (0.8%) initially positive. Among those, 3 were confirmed by alternate NAT, 17 were not confirmed, and 1 had an invalid alternate NAT result. The rate of SARS-CoV-2 RNAemia in deceased tissue donors is approximately 1 per 1000, and it is unknown whether this RNAemia reflects the presence of infectious virus. Given these results, the risk of transmission through tissue is thought likely to be low.

The current COVID-19 disease pandemic has delayed nonurgent orthopaedic procedures to adequately care for those affected by the severe acute respiratory syndrome coronavirus 2, resulting in a backlog in orthopaedic surgical care. As the capacity for orthopaedic surgeries expands or contracts, allocation of limited resources in a manner that adequately reflects medical necessity and urgency is paramount. An orthopaedic surgery-specific prioritization schema with proven reliability is lacking. The primary aim of this study was to assess the reliability of a newly developed prioritization list used for the phased reinstatement of orthopaedic surgical procedures during the COVID-19 pandemic and afterward. The secondary aim was to report its implementation. A consensus-based, orthopaedic surgery-specific, tiered prioritization list reflecting various levels of urgency was created by a committee of orthopaedic surgeons covering all subspecialties and representing academic, multispecialty, and private community practices. Reliability was tested for 63 randomized cases representing all orthopaedic subspecialties. Four raters evaluated the cases independently at two separate time points, at least one week apart. Fleiss kappa was used to assess intrarater and interrater agreement. Implementation were assessed by surveying both surgeons and the surgery scheduling administrative personnel at each surgical facility within a large health system for any adoption issues. Case distributions within tiers 1, 2, 3, and 4 were 35%, 14%, 27%, and 24%, respectively. Interrater agreement ranged from 0.63 (95% confidence interval [CI] 0.57 to 0.69) to 0.72 (95% CI 0.66 to 0.78) for the ratings. Intrarater reliability ranged from 0.62 to 1.0. The highest levels of agreement were in tiers 1, 4, and the subspecialties oncology and foot/ankle. The time from development to full scale adoption and implementation by all orthopaedic surgeons was rapid. This tiered prioritization list for orthopaedic procedures is both adoptable and reliable during the phased reinstatement of procedures during the COVID-19 pandemic and afterward. Further refinements may enhance utility. Reliability study: Level I (Evid Based Spine Care J 2014 October;5(2):166. doi: 10.1055/s-0034-1394106).

Abstract Background The KT Challenge program supports health care professionals to effectively implement evidence-based practices. Unlike other knowledge translation (KT) programs, this program is grounded in capacity building, focuses on health care professionals (HCPs), and uses a multi-component intervention. This study presents the evaluation of the KT Challenge program to assess the impact on uptake, KT capacity and practice change. MethodsThe evaluation used a mixed-methods, time-series design involving surveys and review of documents such as teams’ final reports. Online surveys collecting both quantitative and qualitative data were deployed at four time points (after both workshops, six months into implementation, and at the end of the two-year funded projects) to measure KT capacity ( knowledge, skills and confidence), and impact on practice change. Qualitative data was analyzed using a general inductive approach and quantitative data was analysed using non-parametric statistics. ResultsParticipants reported statistically significant increases in knowledge and confidence across both workshops, at the 6-month mark of their projects, and at the end of their projects. In addition, at the 6-month check-in, practitioners reported statistically significant improvements in their ability to implement practice changes. In the first cohort of the program, of the teams who were able to complete their projects, half were able to show demonstrable practice changes. ConclusionsThe KT Challenge was successful in improving the capacity of HCPs to implement evidence-based practice changes and has begun to show demonstrable improvements in a number of practice areas. The program is relevant to a variety of HCPs working in diverse practice settings and is relatively inexpensive to implement. Like all practice improvement programs in health care settings, a number of challenges emerged stemming from the high turnover of staff and the limited capacity of some practitioners to take on anything beyond direct patient care. Efforts to address these challenges have been added to subsequent cohorts of the KT Challenge program and ongoing evaluation will examine if they are successful. The KT Challenge program has continued to garner great interest among practitioners, even in the midst of dealing with the COVID-19 pandemic, and shows promise for organizations looking for better ways to mobilize knowledge to improve patient care and empower staff. This study contributes to the implementation science literature by providing a description and evaluation of a new model for embedding KT practice skills in health care settings.

Introduction:The fragility index (FI) is a powerful tool that can be used to assess the statistical strength of a study outcome. This metric is defined as the number of patients who would need to have an alternative outcome to convert a clinical trial result from statistically significant to not statistically significant, or vice versa. No studies to date have used the FI to evaluate surgical and procedural clinical trials in the orthopaedic oncology literature. The primary purpose of this study was to use the FI to evaluate the statistical strength of widely cited surgical and procedural clinical trials in orthopaedic oncology.Methods:We performed a PubMed search for orthopaedic oncology clinical trials in high impact orthopaedics–focused, oncology-focused, and general medicine journals. For each study included in this analysis, we calculated the FI for all identified dichotomous, categorical outcomes.Results:We identified 23 studies with 48 outcomes. Twelve of these outcomes were statistically significant, with a median FI of two. Nine studies addressed the number of patients lost to follow up, and the FI was less than the number of patients lost to follow up for most outcomes (60%) in these studies.Conclusions:The orthopaedic oncology literature has substantial statistical fragility, likely explained by a high number of patients lost to follow up and small sample sizes. More multicenter, cooperative studies are necessary to increases the robustness of clinical research in orthopaedic oncology.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O’ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O’BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man’s best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman