The overall goal of the present study is to resurface a diseased femoral condyle in an ovine model of unicompartmental osteoarthritis (OA). For patients suffering from unicompartmental OA of the knee, 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, which use only synthetic materials. To overcome these deficiencies, we have developed a tissue-sparing technique that involves a novel tissue engineering therapy for unicondylar resurfacing. Our approach is based on a multifunctional, hybrid implant that has 2 components: a high-performance three-dimensionally (3D) woven scaffold that mimics the biomechanical properties of native articular cartilage and a novel cartilage inducing bioactive biomaterial derived solely from articular cartilage, or cartilage derived matrix (CDM). In this combination, th 3D woven architecture conforms to the anatomical curvature of the condyle and replicates many of the inhomogeneous, anisotropic, and viscoelastic mechanical properties of articular cartilage, while the CDM provides a cost effective means to potently and rapidly induce adult stem cell chondrogenesis. The following groups will be evaluated: 1) a positive osteoarthritic control group (induction of OA only), 2) an acellular treatment group (anatomically shaped scaffold only), and 3) a tissue-engineered treatment group (anatomically shaped, ex vivo cultured implant with autologous ovine mesenchyme derived stem cells or MSCs). All groups will be evaluated at 3, 6, 9, and 12-month time points following repair through clinically relevant measures of function, pain, and imaging using X-Rays and MRI. MRI will specifically be performed on each sheep 6 months after the repair procedure and after sacrifice to assess cartilage repair and total joint health. At sacrifice, the histological and biomechanical propertie 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 osteoarthritis, as well as for adverse inflammatory reactions and to test for wear debris in the joint. The findings of the study will provide insight nto clinical, imaging, and serum/synovial fluid biomarkers that may provide additional information on the predictive validity of such measures in knee OA.
The aim of this project is to study a multifunctional hybrid 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 novelty of this work involves the combination of high-performance three-dimensionally woven scaffold that is designed to withstand joint loading and a bioactive cartilage-derived matrix that is conducive to cartilage regeneration. This study will evaluate this novel multifunctional composite in a clinically relevant model of osteoarthritis.
