Modifying muscle remodeling following Achilles tendon ruptures

改变跟腱断裂后的肌肉重塑

• 批准号: 10581525
• 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/10581525
• 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; Funding; Gastrocnemius Muscle; Goals; Grant; Histology; Home; Human; Human Subject Research; Image; Immobilization; Infiltration; Injury; Institution; 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; career development; clinical effect; clinical translation; clinically relevant; dosage; experience; experimental study; follow-up; foot; healing; improved; muscle physiology; muscular structure; novel; patient population; post-doctoral training; preservation; repaired; research faculty; 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.

项目摘要 候选人：巴克斯特博士获得了骨科生物力学的运动机能学和博士后培训的博士学位。 他的长期目标是成为一名专注于改善患者结果的独立研究人员 通过跨学科研究框架（1）使用小动物模型来识别肌腱损伤 为了（2）优化测试的治疗 在对照临床试验中。因此，该提议的目的是让他获得必要的培训 小型动物模型，超声成像，肌肉生理和实验室技术来定义 控制肌肉刺激性重塑的生物力学机制对运动功能有利。 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 指导小型动物模型，实验室技术，并提供职业发展培训。博士。 Sehgal，Khurana，Farber和Thelen将担任联合主管，并在超声波上提供动手培训 成像，肌肉生理，手术技术和临床翻译以及非侵入性负荷测量， 分别。 Baxter博士还将定期参加专注于研讨会，研讨会和课程。 生物统计学，生物工程，医学成像，肌肉生理学，赠款写作和职业发展； 每年在两个国家会议上举行；以及继续教育负责任的研究。 环境：宾夕法尼亚大学是McKay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），这是一个17,500 FT2研究空间，配备了良好的建议 培训和研究计划。 PCMD并托管了几项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主机均 医学成像，肌肉生理，生物工程和专业发展的每周/每月研讨会。 研究：这项拟议的工作将挑战当前的范围肌腱破裂是孤立的 肌腱受伤。中心假设是肌肉刺激张力会引发肌肉的前反馈回路 愈合过程中的重塑和肌腱伸长。为了检验这个新的假设，将完成3个目标。目的 1将建立跟腱破裂和手术修复对肌肉组成和肌腱的影响 整个肌腱愈合的生物力学。 AIM 2将定义肌腱张力在肌肉重塑中的作用 使用临床上与临床相关的脚加载装置和进行性拉伸。 AIM 3将修改肌腱伸长 通过使用无损的肌肉刺激刺激肌肉重塑，跟进跟腱破裂。 拉伸协议。测试这些目标将为后续R01生成关键的初步数据，以优化 减轻有害肌肉的重塑和保留功能，临床上与临床相关的负载范例。 机构对候选人的承诺：Baxter博士已获得启动资金，实验室空间和 研究人员已被他的部门批准晋升为研究教师。