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.

该研究金将支持泰勒·劳森先生在 波士顿大学（BU）Mark Grinstaff博士（生物材料和聚合物化学）的赞助， Brian Snyder博士（生物力学和软骨修复）和Michael Albro博士（软骨ECM）的指导 生物学和生物力学）。本提案的研究目的是解决骨关节炎的需求 治疗该建议集中在一种新型的互穿聚合物网络（IPN）上，该网络增强了聚合物的聚合性能。 现有的软骨框架，并模仿糖胺聚糖（GAG）， 水通过健康组织中的固定电荷，目的是恢复退化组织的抗压强度， 软骨目的1评估IPN对保持机械性能、蠕变恢复以及 防止软骨组织磨损，验证IPN的能力，以恢复功能性能， 骨关节炎软骨目的2表征IPN在经处理的离体软骨外植体中的分布 使用磁共振成像。目的3评价IPN抑制活软骨退变的能力 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来移植。 Grinstaff，Snyder和Albro将继续定期与该研究员会面，作为他的一部分。 个性化的三年培训计划，其中包括：1）高分子合成，细胞生物学，体外培养 和体内机械测试，以及先进的成像技术; 2）报名参加两个额外的课程- 波士顿大学医学院的“实验设计和统计方法”和“人类病理学” 在哈佛医学院”; 3）研究一种新的聚合物治疗恢复骨关节炎软骨; 4） 基础科学家和临床医生的指导; 5）负责任的研究行为培训; 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）准备并在当地和国家 会议，以分享他的成果和建立专业网络;和，9）指导他的专业培训， 他个人发展计划的框架。这项研究和培训计划提供了 这位研究员有一个独特的机会来学习，为聚合物治疗学做出贡献，并提高他的 作为一名科学家/工程师，成为一名教授。该奖学金为以下方面提供资源： 指导和跨学科项目设计。