Because chondrocytes in culture are phenotypically unstable, techniques to grow tissue-engineered cartilage for the repair of injured or arthritic joints have met with limited success. Using human donor chondroctyes, we have developed an innovative method for producing what we call neocartilage, a viable, biomechanically stable tissue that we plan to commercialize for the repair of chondral defects in knee joints. Unlike native adult cartilage, which has no capacity for continued growth or repair, the chondrocytes in our neocartilage continue to produce cartilage molecules, resulting in a cartilage tissue that has the potential to repair chondral defects resulting from trauma. In this proposal , we will optimize tissue culture techniques needed for neocartilage production. As a preface to the transplantation studies, we will optimize methods for fixation of neocartilage allografts to the host tissue. In addition, we will evaluate the structural, biochemical, and biomechanical properties of the neocartilage allografts both pre- and post- transplanation in a weight-bearing sheep model. This proposal is unique because it combines biomechanical and biochemical methods of evaluating integrative repair of cartilage defects. We anticipate that upon completion of this proposal, the necessary data will be available to design a pre-clinical study for presentation to the FDA. PROPOSED COMMERCIAL APPLICATION: Our IstoCyte neocartilage has the potential to repair damaged chondral lesions in injured joints perhaps preventing these lesions from destroying bone and cartilage. Furthermore, the neocartilage allograft can offer arthritis patients an alternative to current therapies, perhaps preventing osteoarthritis or delaying total joint replacement.