GAG Mimetic Interpenetrating Network for the Repair of Osteoarthritic Cartilage

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This fellowship will support the interdisciplinary research and training of Mr. Taylor Lawson under the sponsorship of Boston University's (BU) Dr. Mark Grinstaff (biomaterials, and polymer chemistry), and co- mentorship with Dr. Brian Snyder (biomechanics and cartilage repair) and Dr. Michael Albro (cartilage ECM and biology, and biomechanics). The research aim of this proposal addresses the need for an osteoarthritis treatment. This proposal focuses on a novel interpenetrating polymer network (IPN), which augments the existing cartilage framework and mimics the glycosaminoglycans (GAGs) that interpenetrate and attract water via fixed charges in healthy tissue with the goal of restoring compressive strength to degenerated cartilage. Aim 1 assesses the IPN contribution to preserving mechanical properties, creep-recovery, and to preventing cartilage tissue wear, validating the IPN's ability to restore the functional performance of osteoarthritic cartilage. Aim 2 characterizes the distribution of the IPN in treated ex vivo cartilage explants using magnetic resonance imaging. Aim 3 evaluates the IPN's ability to inhibit degeneration of live cartilage explants by supporting mechanical loads and limiting chondrocyte exposure to catabolic cytokines. Drs. Grinstaff, Snyder, and Albro will continue to meet regularly with the fellow as part of his personalized three-year training plan, which includes: 1) training in polymer synthesis, cell biology, in vitro and in vivo mechanical testing, and advanced imaging techniques; 2) enrolling in two additional courses – “Experimental Design and Statistical Methods” at Boston University Medical School and “Human Pathology” at Harvard Medical School”; 3) researching a novel polymer therapeutic to restore osteoarthritic cartilage; 4) mentoring by basic scientists and clinicians; 5) training in responsible conduct of research; 6) attending Children's Hospital Orthopeadic Grand Rounds; 7) attending seminars in the Mechanical Engineering, Chemistry, and Biomedical Engineering Departments; 8) preparing for and presenting at local and national conferences to share his results and build professional networks; and, 9) guiding his professional training in the framework of his individual development plan. This combined research and training program provides the fellow a unique opportunity to learn, to contribute to polymer therapeutics, and to advance his development as a scientist/engineer to becoming a Professor. This fellowship establishes resources for mentoring and an interdisciplinary project design.