The goal of the proposed research is to develop a tissue-engineered osteochondral construct that will result in functional resurfacing of the entire articular surface of the patella in dogs. Our long-term objective is to develop a clinically applicable biologic arthroplasty approach for treating articular cartilage loss due to injury or osteoarthritis in humans. The natural response of articular cartilage to insult and injury is variable and, at best, unsatisfactory. Current surgical approaches for addressing this unsatisfactory response involve synthetic arthroplasty, autogenous or allogeneic grafts, and tissue stimulation techniques. Unfortunately, current treatment options are limited by prosthetic wear, loosening, and infection, availability, poor integration, and poor anatomic size and shape matching. These limitations results in dysfunction, disability, morbidity, and financial and emotional costs to patients, the health-care industry, government agencies, and tax-payers. A potential means for overcoming these issues is to develop tissue-engineered osteochondral constructs matched to patients that will resurface the entire articular surface(s) affected. Initial work through our group's collaborative partnership suggests that functional osteochondral constructs can be created using advanced imaging, established chondrocyte culture techniques, and in vitro tissue engineering methodology. Further, these constructs can be created using allogeneic chondrocytes and be successfully implanted into articular cartilage defects in the knees of dogs, resulting in tissue viability and integration. Based on these data, we hypothesized that tissue-engineered osteochondral constructs can be created that will allow for functional resurfacing of the entire articular surface of the patella in dogs as assessed by lameness scoring, clinical imaging, biochemical, biomechanical, and histologic outcome measures. In testing this hypothesis, our specific aims are to: 1) Optimize in vitro culture of canine osteochondral constructs using a well-defined culture medium and growth factor supplementation for in vivo cartilage resurfacing of the patella, and 2) Assess in vivo implantation of engineered patellar osteochondral constructs implanted into knees of adult dogs. Completion of these aims will provide the basis for pursuing our stated long-term objective, which will have the potential for providing a clinical tool for repair of large articular cartilage defects in patients thereby delaying, or even eliminating, the need for artificial joint arthoplasty. ? ? ?
