GAG Mimetic Interpenetrating Network for the Repair of Osteoarthritic Cartilage

用于修复骨关节炎软骨的 GAG 模拟互穿网络

• 批准号: 9758973
• 负责人: Taylor Lawson
• 金额: $ 4.24万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9758973
• 关键词: Acute; Address; Adult; Advanced Development; Affect; American; Biocompatible Materials; Biology; Biomechanics; Biomedical Engineering; Boston; Cartilage; Cartilage Diseases; Cell Survival; Cellular biology; Charge; Chemistry; Choline; Chondrocytes; Chondrogenesis; Chronic; Clinical; Collagen; Compressive Strength; Degenerative polyarthritis; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Engineering; Enrollment; Equilibrium; Experimental Designs; Exposure to; Extracellular Matrix; Fellowship; Fingers; Friction; Future; Genetic Markers; Geometry; Glycosaminoglycans; Goals; Hip region structure; Histologic; Human; Human Pathology; Hyaline Cartilage; Hybrids; Hydration status; Imaging Techniques; Impairment; In Vitro; Individual; Institution; Interdisciplinary Study; Joints; Kinetics; Knee; Learning; Liquid substance; Lubrication; Magnetic Resonance Imaging; Measures; Mechanical Stress; Mechanics; Mentors; Mentorship; Metacarpal bone; Methods; Microscopy; Modulus; Molecular Biology; Pain; Pediatric Hospitals; Performance; Perfusion; Phenotype; Plug-in; Polymer Chemistry; Polymers; Positioning Attribute; Procedures; Property; Protocols documentation; Quality of life; Recovery; Relaxation; Research; Research Proposals; Research Training; Resistance; Resources; Rotation; Sampling; Scientist; Signal Transduction; Slice; Solid; Spectroscopy, Fourier Transform Infrared; Statistical Methods; Stress; Surface; Synovial Fluid; Techniques; Testing; Therapeutic; Tissues; Training; Training Programs; Universities; Ursidae Family; Water; Weight-Bearing state; articular cartilage; career; career networking; cartilage cell; cartilage repair; cytokine; daily functioning; design; improved; in vivo; insight; joint injury; mechanical load; mechanical properties; medical schools; mimetics; novel; osteochondral tissue; patient mobility; patient population; preservation; prevent; professor; programs; repaired; research study; response; responsible research conduct; symposium

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.

该奖学金将支持泰勒·劳森先生的跨学科研究和培训 波士顿大学（BU）Mark Grinstaff博士（生物材料和聚合物化学）的赞助以及共同 Brian Snyder博士（生物力学和软骨维修）和Michael Albro博士（软骨ECM 生物学和生物力学）。该提案的研究目的旨在解决骨关节炎的需求 治疗。该提案重点是一种新型的互穿聚合物网络（IPN），该网络增加了 现有的软骨框架并模仿互渗酸盐和吸引力的糖胺聚糖（gags） 通过健康组织中的固定电荷水，目的是恢复抗压强度 软骨。 AIM 1评估IPN对保留机械性能，蠕变恢复和对的贡献 防止软骨组织磨损，从而验证IPN恢复功能性能的能力 骨关节炎软骨。 AIM 2字符在经过处理的离体软骨外植体中IPN的分布 使用磁共振成像。 AIM 3评估IPN抑制活软骨变性的能力 通过支持机械载荷和限制软骨细胞暴露于分解代谢细胞因子的外植体。 博士。 Grinstaff，Snyder和Albro将继续定期与同伴会面 个性化的三年培训计划，其中包括：1）聚合物合成，细胞生物学，体外培训 以及体内机械测试和高级成像技术； 2）参加另外两门课程 - 波士顿大学医学院和“人类病理学”的“实验设计和统计方法” 在哈佛医学院”; 3）研究一种新型聚合物疗法以恢复骨关节炎软骨； 4） 基础科学家和临床医生的指导； 5）负责任的研究培训； 6）参加 儿童医院骨科大弹； 7）参加机械工程的下水道， 化学和生物医学工程部门； 8）准备并在本地和国家展示 会议分享他的结果并建立专业网络；以及，9）指导他的专业培训 他的个人发展计划的框架。这个联合研究和培训计划提供了 这位家伙是学习，为聚合物疗法做出贡献并推进他的独特机会 作为科学家/工程师成为教授的发展。该奖学金为 指导和跨学科项目设计。