Modifying muscle remodeling following Achilles tendon ruptures

改变跟腱断裂后的肌肉重塑

• 批准号: 10360517
• 负责人: Josh Baxter
• 金额: $ 12.62万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10360517
• 关键词: Acute; Animal Model; Biological; Biomechanics; Biomedical Engineering; Biometry; Clinical; Clinical Trials; Continuing Education; Contracture; Controlled Clinical Trials; Data; Decision Making; Development; Devices; Doctor of Philosophy; Educational workshop; Environment; Feedback; Fiber; Flexor; Foundations; Funding; Gastrocnemius Muscle; Goals; Grant; Histology; Home; Human; Human Subject Research; Image; Immobilization; Infiltration; Injury; Interdisciplinary Study; Intervention; Kinesiology; Laboratories; Laboratory Research; Lead; Length; Link; Literature; Measurement; Mechanics; Medical Imaging; Mentors; Modeling; Muscle; Muscular Atrophy; Musculoskeletal; Musculoskeletal Diseases; Operative Surgical Procedures; Orthopedics; Pathology; Patient-Focused Outcomes; Patients; Pennsylvania; Protocols documentation; Rattus; Research; Research Personnel; Rest; Role; Rupture; Sarcomeres; Services; Skeletal Muscle; Stretching; Structure; Techniques; Tendon Injuries; Tendon Transfer; Tendon structure; Testing; Tissues; Training; Ultrasonography; United States National Institutes of Health; Universities; Work; Writing; achilles tendon; base; career development; clinical effect; clinical translation; clinically relevant; dosage; experience; experimental study; faculty research; follow-up; foot; healing; improved; muscle physiology; muscular structure; novel; patient population; post-doctoral training; preservation; repaired; response; responsible research conduct; skills; soft tissue; symposium; targeted treatment; tendon rupture; treatment optimization; treatment planning

PROJECT SUMMARY Candidate: Dr. Baxter received his PhD in kinesiology and post-doctoral training in orthopaedic biomechanics. His long-term goal is to become an independent researcher focused on improving patient outcomes following tendon injuries through an interdisciplinary research framework (1) using small animal models to identify mechanisms that govern muscle-tendon healing and function in order to (2) optimize treatments that are tested in controlled clinical trials. Therefore, the objective of this proposal is for him to acquire the training necessary in small animal models, ultrasound imaging, muscle physiology, and laboratory techniques to define the biomechanical mechanisms that govern muscle-tendon remodeling that are advantageous to locomotor function. Mentoring Committee and Training Plan: Dr. Soslowsky, will serve as primary mentor and provide structured mentoring in of small animal models, laboratory techniques, and provide career development training. Drs. Sehgal, Khurana, Farber, and Thelen will serve as co-mentors and provide hands-on training in ultrasound imaging, muscle physiology, surgical techniques and clinical translation, and non-invasive load measurement, respectively. Dr. Baxter will also participate regularly in seminars, workshops, and coursework focused on biostatistics, bioengineering, medical imaging, muscle physiology, grant writing, and career development; present at two national conferences each year; and continuing education on responsible conduct of research. Environment: The University of Pennsylvania is home to the McKay Orthopaedic Research Laboratory and Penn Center for Musculoskeletal Disorders (PCMD), a 17,500 ft2 research space that is well-equipped for the proposed training and research plan. The PCMD and hosts several NIH supported core services focused on musculoskeletal research, which include histology, biomechanics, and imaging. Both the PCMD and Penn host weekly/monthly seminars in medical imaging, muscle physiology, bioengineering, and professional development. Research: This proposed work will challenge the current paradigm that Achilles tendon ruptures are isolated tendon injuries. The central hypothesis is that muscle-tendon tension initiates a forward-feedback loop of muscle remodeling and tendon elongation during healing. To test this novel hypothesis, 3 aims will be completed. Aim 1 will establish the effects of Achilles tendon rupture and surgical repair on muscle composition and tendon biomechanics throughout tendon healing. Aim 2 will define the role of tendon tension on muscle remodeling using a clinically-relevant foot loading device and progressive stretching. Aim 3 will modify tendon elongation following Achilles tendon rupture by stimulating muscle remodeling using non-damaging muscle-tendon stretching protocols. Testing these aims will generate critical preliminary data for a follow-up R01 that optimizes clinically-relevant loading paradigms that mitigate detrimental muscle remodeling and preserves function. Institutional Commitment to Candidate: Dr. Baxter has been provided start-up funds, laboratory space, and research personnel and has been approved to be promoted to the research faculty track by his department.

项目概要 候选人：巴克斯特博士获得了运动机能学博士学位和骨科生物力学博士后培训。 他的长期目标是成为一名独立研究人员，致力于改善以下患者的治疗结果 通过跨学科研究框架（1）使用小动物模型来识别肌腱损伤 控制肌肉肌腱愈合和功能的机制，以便 (2) 优化经过测试的治疗方法 在对照临床试验中。因此，本提案的目的是让他获得以下方面所需的培训： 小动物模型、超声成像、肌肉生理学和实验室技术来定义 控制有利于运动功能的肌肉肌腱重塑的生物力学机制。 指导委员会和培训计划：Soslowsky 博士将担任主要导师并提供结构化的指导 指导小动物模型、实验室技术，并提供职业发展培训。博士。 Sehgal、Khurana、Farber 和 Thelen 将担任联合导师并提供超声波实践培训 成像、肌肉生理学、手术技术和临床转化以及非侵入性负荷测量， 分别。巴克斯特博士还将定期参加研讨会、讲习班和课程，重点关注 生物统计学、生物工程、医学成像、肌肉生理学、资助写作和职业发展； 每年出席两次全国会议；以及负责任的研究行为的继续教育。 环境：宾夕法尼亚大学是麦凯骨科研究实验室和宾夕法尼亚大学的所在地 肌肉骨骼疾病中心 (PCMD)，一个占地 17,500 平方英尺的研究空间，设备齐全，可用于拟议的研究 培训和研究计划。 PCMD 并主持多项 NIH 支持的核心服务，重点关注 肌肉骨骼研究，包括组织学、生物力学和成像。 PCMD 和 Penn 主机 每周/每月举办医学影像、肌肉生理学、生物工程和专业发展研讨会。 研究：这项拟议的工作将挑战当前跟腱断裂是孤立的范式 肌腱损伤。中心假设是肌肉肌腱张力启动肌肉的前反馈回路 愈合过程中的重塑和肌腱伸长。为了检验这一新颖的假设，将完成 3 个目标。目的 1 将确定跟腱断裂和手术修复对肌肉成分和肌腱的影响 整个肌腱愈合过程中的生物力学。目标 2 将定义肌腱张力对肌肉重塑的作用 使用临床相关的足部负重装置和渐进式拉伸。目标 3 将改变肌腱伸长率 通过使用非损伤性肌腱刺激肌肉重塑来治疗跟腱断裂 拉伸协议。测试这些目标将为后续 R01 优化生成关键的初步数据 临床相关的负荷范例，可减轻有害的肌肉重塑并保留功能。 机构对候选人的承诺：巴克斯特博士已获得启动资金、实验室空间和 研究人员，并已被所在部门批准晋升为研究教师。