Research Core

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Research Core Summary Achilles tendinopathy is a painful, debilitating, and chronic tendon condition. Patients receive physical therapy as the first step in conservative treatment. These physical therapy protocols – which are the only non- surgical treatments paid for by most insurers – prescribe mechanical loads as a therapeutic agent. However, sixty percent of patients continue to report painful symptoms after 5 years, and fifty percent of patients seek surgical treatment after conservative treatment fails. Therefore, maximizing the therapeutic effectiveness of mechanical loading is critical towards improving patient outcomes and reducing the need for costly and often ineffective surgical treatments. To meet this unmet clinical need, our proposed Research Projects will establish the mechano-responsiveness of tendon cells throughout tendinopathy disease progression and elucidate the mechanotransductive mechanisms that regulate cell fate and tissue homeostasis to attenuate disease progression and improve tendon healing. To accelerate clinical translation, the overall objective of this Achilles Tendinopathy Tissue Core is to provide patient and clinically relevant rat tendon samples, ranging from healthy to degenerated, combined with the most complete set of longitudinal in vivo assays to maximize the translational impact of our Research Projects proposed in this P50 application, as well as numerous NIH funded projects at Penn aimed at improving tendon healing by our P50 team of investigators. In Aim 1, we will retrieve patient tissues to investigate end-stage Achilles tendinopathy mechano-sensitivity. In Aim 2, we will leverage a tendinopathy preclinical model to investigate disease pathogenesis. These 2 aims will utilize an extensive battery of in vivo assays including gait analysis, loading monitoring, joint mechanics, ultrasound imaging, and metabolomics to maximize research translation from our exciting Research Projects to clinical populations. In Aim 3, we will develop novel techniques to translate preclinical findings to improve patient care. These translational tools are necessary for follow-up animal experiments and clinical trials that will test the effectiveness of personalized rehabilitative care at improving tendon healing and outcomes while addressing existing inequitable care delivery for patients with Achilles tendon injuries. We will accelerate fundamental discovery research and translation through preclinical studies to clinical populations. By establishing the Achilles Tendinopathy Tissue Core, we will provide unique and rigorous techniques and expertise, as well as carefully controlled and characterized study material to tendon researchers locally, and ultimately nationally, while developing critical new technologies to improve patient care in future clinical research. We selected Achilles tendinopathy to address a common and debilitating condition while demonstrating the proof-of-concept model paradigm that leveraging patient tissues with preclinical models will accelerate fundamental discovery to more effective and equitable musculoskeletal care.