GAG Mimetic Interpenetrating Network for the Repair of Osteoarthritic Cartilage

这笔研究金将支持泰勒·劳森先生的跨学科研究和培训 赞助波士顿大学(BU)Mark Grinstaff博士(生物材料和聚合物化学)，并与 与Brian Snyder博士(生物力学和软骨修复)和Michael Albro博士(软骨ECM)的指导 以及生物学和生物力学)。这项建议的研究目的是解决骨关节炎的需要。 治疗。这一建议的重点是一种新型的互穿聚合物网络(IPN)，它增强了 现有的软骨框架，并模仿相互穿透和吸引的糖胺多聚糖(GAG) 通过固定电荷在健康组织中提供水分，目的是恢复退化的抗压强度 软骨。目标1评估IPN在保持机械性能、蠕变恢复和 防止软骨组织磨损，验证IPN恢复关节功能的能力 骨关节炎软骨。目的研究异丙肾上腺素在体外培养软骨中的分布 使用核磁共振成像。目的3评价IPN抑制活体软骨退变的能力 通过支持机械负荷和限制软骨细胞暴露于分解代谢细胞因子。 Grinstaff、Snyder和Albro博士将继续定期与这位研究员会面，这是他 个性化三年培训计划，包括：1)聚合物合成、细胞生物学、体外培养方面的培训 和活体机械测试，以及先进的成像技术；2)报名参加另外两门课程- 波士顿大学医学院的《实验设计与统计方法》和《人类病理学》 在哈佛医学院；3)研究一种新的聚合物疗法来修复骨关节炎软骨；4) 基础科学家和临床医生的指导；5)负责任地进行研究的培训；6)参加 儿童医院骨科大查房；7)参加机械工程研讨会， 化学和生物医学工程系；8)在地方和国家筹备和展示 分享他的成果并建立专业网络的会议；以及，9)指导他在 他个人发展计划的框架。这一研究和培训相结合的计划提供了 这位研究员有一个独特的机会来学习，为聚合物疗法做出贡献，并促进他的 从科学家/工程师到教授的发展。这项奖学金为以下项目建立了资源 指导和跨学科的项目设计。

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.