DESCRIPTION (provided by applicant): Osteoarthritis (OA) is characterized by progressive degeneration of articular cartilage, subchondral bone, and other joint tissues, resulting in a major reduction in quality of life and substantial economic costs. Articular cartilage defects are associated with accelerated OA progression and are surprisingly common, with a reported incidence of over 60% in arthroscopically examined painful knees. At least 500,000 cartilage repair procedures are estimated to be performed annually in the United States alone. As lack of lateral cartilage integration is a crucial factor leading to graft complications and failure, approaches including suturing, adhesives, and photothermal tissue welding have been explored to enhance graft integration. Our preliminary studies demonstrate the feasibility of light-activate photochemical cartilage bonding as a potential strategy for rapidly producing durable cartilage-to-cartilage bonding. The goal of this study is to extend this promising preliminary work to develop clinically relevant photochemical bonding protocols for treating articular cartilage defects through a series of evaluations culminating in an in vivo evaluation. Our specific aims are: 1) Benchtop phase: Optimize photosensitizer, surface treatment and exposure conditions to achieve rapid photochemical bonding of articular cartilage; 2) In vitro phase: Determine photochemical bond durability and effects of treatment on cell metabolism and extracellular matrix deposition in an in vitro cartilage defect repair model; 3) In vivo phase: Determine the effects of photochemical bonding on cartilage integration in vivo in a rabbit osteochondral allograft model. The significance of this work is in the potential to improve outcomes in the growing number of cartilage repair procedures, with potential application to both natural and engineered tissue grafts. The innovation of this work is in the development of a clinically feasibl photochemical bonding approach suitable for treating full thickness cartilage defects and achieving durable lateral integration.

PUBLIC HEALTH RELEVANCE: If left untreated, localized cartilage defects due to injury or focal degeneration typically lead to osteoarthritic degradation of the entire joint. One of the challenges facing existing and new approaches to repair or regenerate these defects is the difficulty in achieving stable integration between an implanted graft and the surrounding cartilage. This work aims to develop a photochemical bonding approach suitable for rapid, intraoperative generation of a durable bond between implanted and host cartilage. After a series of laboratory studies to identify suitable treatment parameters to produce durable cartilage-to-cartilage bonding while minimizing cell death and adverse metabolic responses, we will evaluate the effectiveness of the photochemical bonding procedure for adhering transplanted osteochondral (cartilage/bone) grafts in a rabbit osteochondral allograft model.