Unicondylar Resurfacing in an Ovine Osteoarthritis Disease Model

DESCRIPTION provided by applicant The treatment of large cartilage lesions is a difficult clinical problem for which there are few good solutions Left untreated these lesions tend to degenerate to chronic pain and osteoarthritis OA ultimately requiring a total joint replacement For patients suffering from knee OA and in particular unicompartmental OA unicondylar knee arthroplasty UKA is an available first line treatment option that provides many potential advantages over more common total knee replacement procedures However this approach remains controversial due to variable clinical results and high rates of revision associated with current implant designs To overcome the pitfalls associated with current implant designs we have developed a novel tissue engineering therapy for unicondylar resurfacing for knee OA The overall goals of this study are two fold Phase I to repair large osteochondral defects in the knee for which current treatment paradigms are currently contraindicated and Phase II to resurface a diseased femoral condyle in an ovine model of unicompartmental OA Our approach for both phases is based on a high performance three dimensionally D woven scaffold that mimics the biomechanical properties of native articular cartilage at the initial time of cell seeding thus providing a highly functional implant Its unique woven architecture forms to the anatomical curvature of the condyle provides an environment that encourages cell growth and differentiation and is capable of integrating with subchondral bone In Phase I efficacy of the technology will be evaluated in a large full thickness cartilage defect located in the medial condyle of the knee The following groups will be evaluated a defect only control group an acellular scaffold treatment group autologous mesenchyme derived stem cell MSC seeded scaffold group and a tissue engineered treatment group ex vivo cultured scaffold with autologous MSCs At months the regenerative response of all groups will be evaluated histologically and biomechanically The most successful treatment will then be translated to Phase II where an anatomically condyle shaped implant will be used to treat OA All animals in Phase II will be evaluated at and months following repair Functional measurements will be taken pre and postoperatively to evaluate joint function and comfort while sequential radiographs and MRI will be used to assess any morphological changes Histological and biomechanical properties of the joint tissues collected from the treated joint will be compared to those from the contralateral limb negative control to quantify degradative changes Serum synovial fluid and synovium will be analyzed for biomarkers of OA as well as for adverse inflammatory reactions and to test for wear debris in the joint This study will primarily provide valuable data on the ability of out technology to treat a range of cartilage pathology ranging from large cartilaginous defects to unicompartmental OA Secondarily the findings of the study will provide insight into clinical imaging and serum synovial fluid biomarkers that may provide additional information on the predictive validity of such measures in knee OA PUBLIC HEALTH RELEVANCE The aim of this project is to study a biosynthetic implant that can be used for treatment of cartilage pathologies ranging from large defects to unicompartmental knee osteoarthritis while providing significant advantages over typical knee replacement procedures The basis of this work involves the combination of bone marrow derived adult stem cells and a novel high performance three dimensionally woven scaffold that is designed to withstand joint loading and induce differentiation of the stem cells The ultimate goal of this study is to develop tissue engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases