Unicondylar Resurfacing in an Ovine Osteoarthritis Disease Model

AbstractThe treatment of large cartilage lesions is a difficult clinical problem for which there are few good
solutionsLeft untreatedthese lesions tend to degenerate to chronic pain and osteoarthritisOAultimately
requiring a total joint replacementFor patients suffering from knee OAandin particularunicompartmental
OAunicondylar knee arthroplastyUKAis an available first line treatment option that provides many potential
advantages over more common total knee replacement proceduresHoweverthis approach remains
controversial due to variable clinical results and high rates of revision associated with current implant designsTo overcome the pitfalls associated with current implant designswe have developed a novel tissue
engineering therapy for unicondylar resurfacing for knee OAThe overall goals of this study are two foldPhase Ito repair large osteochondral defects in the kneefor which current treatment paradigms are currently
contraindicatedandPhase IIto resurface a diseased femoral condyle in an ovine model of unicompartmental
OAOur approach for both phases is based on a high performance three dimensionallyDwoven scaffold
that mimics the biomechanical properties of native articular cartilage at the initial time of cell seedingthus
providing a highly functional implantIts unique woven architecture forms to the anatomical curvature of the
condyleprovides an environment that encourages cell growth and differentiationand is capable of integrating
with subchondral boneIn Phase Iefficacy of the technology will be evaluated in a largefull thickness
cartilage defect located in the medial condyle of the kneeThe following groups will be evaluateda defect
only control groupan acellular scaffold treatment groupautologous mesenchyme derived stem cellMSCseeded scaffold groupanda tissue engineered treatment groupex vivo cultured scaffold with
autologous MSCsAtmonthsthe regenerative response of all groups will be evaluated histologically and
biomechanicallyThe most successful treatment will then be translated to Phase II where an anatomically
condyle shaped implant will be used to treat OAAll animals in Phase II will be evaluated atandmonths following repairFunctional measurements will be taken preand postoperatively to evaluate joint
function and comfortwhile sequential radiographs and MRI will be used to assess any morphological changesHistological and biomechanical properties of the joint tissues collected from the treated joint will be compared
to those from the contralateral limbnegative controlto quantify degradative changesSerumsynovial fluidand synovium will be analyzed for biomarkers of OAas well as for adverse inflammatory reactions and to test
for wear debris in the jointThis study will primarily provide valuable data on the ability of out technology to
treat a range of cartilage pathologyranging from large cartilaginous defects to unicompartmental OASecondarilythe findings of the study will provide insight into clinicalimagingand serum synovial fluid
biomarkers that may provide additional information on the predictive validity of such measures in knee OA