The broader impact/commercial potential of this I-Corps project is the development of an in vitro, articular cartilage model for osteoarthritis (OA). This model is designed to increase the likelihood of successful clinical translation of research on the causes of OA into potential treatments. OA often occurs with age or injury and affects over 32.5 million US adults. There are currently no known disease-modifying treatments to stop or reverse the progression of OA – all current treatments are limited to either various methods of pain management or surgical tissue replacement. The proposed technology will advance the translation of OA research by facilitating studies of chondrocytes, the primary cells that cause OA, using traditional and state-of-the-art genomic, proteomic, and imaging techniques. It is expected that the proposed technology will bridge the gap between the 2D and 3D cell culture markets, represented by an annual market of ~$1 billion in the US. Due to the prevalence and crippling nature of OA, joint replacements represent a $19 billion industry annually in the US. In addition to its role in OA treatments, the model may clinical implications in improving outcomes for autologous chondrocyte transplantation, increasing its commercial impact.<br/><br/>This I-Corps project is based on the development of a cell culture platform that improves control over the differentiation of chondrocytes. This control is enabled through the regulation of cell shape via a novel combination of nanotechnology, micropatterning, and mechanically-tunable, thin-film composite materials. Chondrocytes rapidly transform into non-physiological cell types in standard 2D culture systems. More advanced 3D culture systems prevent this problem but introduce difficulties in compatibility with analytical techniques. The proposed technology may act as an egg crate for individual cells, nesting each one in an environment that allows it to maintain its physiological nature without restricting their ability to be studied. The technology may maintain the physiological cell shape of chondrocytes for at least 28 days, four times as long as competing micropatterned technologies. The technology has potential applications in drug development, gene therapy, stem cell medicine, tissue engineering, the elucidation of molecular pathogeneses, and other biomedical applications.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.