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James A. Martin, Associate Professor, Orthopedics & Rehabilitation, University of Iowa, “The Intrinsic Regenerative Capacity of Articular Cartilage”
October 2 @ 12:00 pm - 1:00 pm
Topic: The Intrinsic Regenerative Capacity of Articular Cartilage
Abstract: Articular cartilage lesions caused by common forms of joint trauma contribute to the pathogenesis of post-traumatic osteoarthritis, a profoundly disabling condition for which there is no cure. Spontaneous healing of cartilage lesions is rare and a number of methods designed to overcome its limited regenerative capacity have been developed. Many strategies involve removing damaged cartilage and grafting chondrocytes or stem cells to fill the resulting defect. While patients derive some benefit from these interventions, the procedures carry substantial risks including morbidity associated with cartilage or bone marrow harvests, and the need to grow, or otherwise manipulate cells, ex vivo. Moreover, some procedures, such as chondrocyte implantation, require two surgeries to harvest cartilage and graft the cells. To address these issues, we have developed a strategy that exploits the intrinsic regenerative powers of chondrogenic progenitor cells (CPCs) residing in cartilage. The strategy includes a fibrin-hyaluronic acid hydrogel, which serves as a defect filler and conductor of cell migration. The potent progenitor cell chemotactic factor, stromal-derived factor-1 alpha (SDF-1 alpha), is dissolved in the gel and promotes full cellularization of the defects through CPC chemotaxis. Once the gel is populated, the chondrogenic growth factor transforming growth factor beta-3 is provided either in soluble form or complexed with polylactic co-glycolic acid microparticles that slowly release the peptide, stimulating CPCs to replace the original hydrogel with neo-cartilage that closely approximates the biomechanical and biochemical characteristics of the surrounding cartilage.