Modifying muscle remodeling following Achilles tendon ruptures

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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.