Robert E. Guldberg, Ph.D. (ME, Georgia Institute of Technology) (Advisor)
Todd C. McDevitt, Ph.D. (Gladstone Institute of Cardiovascular Disease)
Thomas J. Koob, Ph. D. (Chief Scientific Officer, MiMedx Group, Inc.)
Johnna S. Temenoff, Ph.D. (BME, Georgia Institute of Technology)
Krishnendu Roy, Ph. D. (BME, Georgia Institute of Technology)
Title: Engineering an Improved Cartilage Repair Strategy Combining Cells and ECM-derived Materials
Cartilage has a limited capacity to heal and regenerate due to its low cellularity and avascular nature. As a result, osteoarthritis (OA) affects nearly 27 million adults in the US and there are no clinically proven disease modifying therapies, leading to nearly half a million total knee replacements annually. Autologous chondrocyte implantation is the only clinically approved cellular therapy for chondral defects in the US, but the inability to expand chondrocytes to sufficient numbers without adversely affecting their phenotype remains a significant problem. Additionally, the multiple inflammatory mediators involved in the initiation and perpetuation of OA hinder the efficacy of cellular therapies. The inherent immunomodulatory capabilities of MSCs offer a potent alternative to conventional drug treatment regimens due to their ability to regulate multiple signaling pathways and cell types of innate and adaptive immunity. The primary objective of this study is to engineer an improved cartilage repair strategy by combining cells and extracellular matrix(ECM)-derived materials. Specifically, this work will (i) develop cartilage-derived microcarriers for chondrocyte expansion (ii) determine the effect of tissue-specific ECM-derived materials on the chondrogenesis, cell expansion, and secretion of anti-inflammatory factors, and (iii) characterize the effect of MSC delivery format, via single cells, spheroids, or ECM-derived microcarriers, on OA progression in a post-traumatic small animal model. This work will increase the scientific community's understanding of the role of ECM-derived materials in influencing cell phenotype and expansion as well as the effect of culture format and delivery on MSC-mediated immunomodulatory activity.