Unicondylar Resurfacing in an Ovine Osteoarthritis Disease Model

Abstract Osteoarthritis (OA) is a leading cause of disability in the developed world, affecting over 30 million adults in the US with an economic burden of over $486 billion per year. Advanced OA is most commonly treated with total joint replacement, but this is suboptimal for younger patients, especially those under 55 who lead an active lifestyle, because of the high occurrence of multiple revision surgeries. For this growing patient population, Cytex is developing implants pairing a patented 3D weaving technology with additive manufacturing to facilitate cartilage and bone regeneration in the joint. The implant is designed to support joint loading immediately at the time of implantation and to allow integration and development of osteochondral tissue. Both an acellular implant and a tissue engineered implant that combines the acellular scaffold with autologous cells have demonstrated in large animal models of OA the capability of repairing osteochondral lesions and restoring pain-free joint function for extended durations. The tissue engineered implant is particularly desirable for patients without a potent endogenous cell source to repopulate the acellular implant and synthesize a mature extracellular matrix in vivo. Cytex has chosen femoroacetabular impingement (FAI) in the hip as a lead indication for a pilot clinical study with the acellular implant. FAI presents in active, young patients, with no good option to repair the resulting osteochondral lesions, which progress into more severe OA. The tissue engineered implant will follow the acellular product into clinical study. Autologous cells, as used in our pre- clinical studies, require time-consuming cell isolation and expansion steps. Instead, Cytex will use allogeneic mesenchymal stem cells (MSCs) derived from bone marrow, which express very low levels of major histocompatibility complex (MHC) class I and class II antigens. To prepare the allogeneic tissue engineered implants for clinical study, Cytex must further develop the tissue engineered implant to overcome specific commercialization hurdles. The goal of this proposal is to address these hurdles: 1) Cytex must identify and develop potency assays that measure the biological activity of the seeded cells and set acceptance criteria for those assays. 2) Cytex will identify cryopreservation and storage conditions for the implants to be available off- the-shelf because surgeons and patients are unlikely to wait several weeks for an implant to be made-to-order. 3) manufacturing of the tissue engineered implants will be transferred to a contract manufacturer that follows the current good manufacturing practices (cGMPs) required for regulatory approval. 4) Cytex, with an experienced regulatory consulting firm, will engage with the US FDA to discuss requirements for clinical study approval. The culmination of this project will be an off-the-shelf tissue engineered implant for cartilage repair that will enable Cytex to broaden its implant portfolio and enable treatment for patients that currently have no good clinical options either because of their advanced age or disease state.