Articular cartilage damage is a growing problem with active and increasingly aging populations. Cartilage, which is critical for frictionless and painless joint motion, has little endogenous repair capability. Aging processes and trauma lead to cartilage degeneration, which can result in osteoarthritis (OA). At least 27 million Americans suffer from OA, and over one million cartilage restoration surgeries are performed each year. Clinically, cartilage is difficult to repair due to its low cellularity, poor native regeneration potential, and lack of blood supply. Tissue engineering uses a combination of materials design and cellular biology to potentiate tissue repair and replacement. The research proposed will focus on two potential candidates for components of a tissue- engineered solution for cartilage damage. Hyaluronic acid (HA) is a hydrophilic polymer of repeating dissacharide units that is highly abundant in the extracellular matrix (ECM) of cartilage and in the synovial fluid of the joint, and provides for much of its mechanical properties and frictionless movement. HA also has potent biological effects in the joint space, including limiting inflammation and stimulating chondrocytes. HA is already used as an injectable symptomatic treatment of OA, but it plagued by issues of high clearance and inconsistent results. We hypothesize that the retention of HA on the articular surface and controlled presentation to cell populations in a cartilage defect will improve cartilage repair and clinical outcomes. This study will have the following specific aims: 1) To develop a new biological synthetic composite material with HA binding capabilities, which can be used to selectively control HA presentation in the joint. 2) This will be evaluated for its ability to improve cartilage repair in vitro through its effects on cellular behavior. 3) Then, it will be evaluated for its ability to induce cartilage repair in vivo in a newly developed OA animal model combined with osteochondral defects. This research will further the understanding the role of HA in the pathogenesis of OA and the potential of controlled ECM presentation to improve cartilage repair outcomes. PUBLIC HEALTH RELEVANCE: The aging populations of the United States and other developed countries are facing a growing number of diseases associated with cartilage damage or degeneration. At least 27 million Americans suffer from osteoarthritis, and more than 300,000 total knee replacements are carried out each year. This research will develop a novel biomaterial to address shortfalls in current cartilage repair strategies.