Research Core

研究核心摘要 跟腱病是一种疼痛、虚弱和慢性肌腱疾病。患者接受体检 治疗是保守治疗的第一步。这些物理治疗方案是唯一的非- 手术治疗由大多数保险公司支付--将机械负荷作为一种治疗剂。然而， 60%的患者在5年后继续报告疼痛症状，50%的患者寻求 保守治疗后手术治疗失败。因此，最大限度地提高治疗效果 机械负荷对于改善患者预后和减少昂贵且经常 手术治疗无效。为了满足这一未得到满足的临床需求，我们建议的研究项目将建立 肌腱细胞在肌腱病疾病进展过程中的机械反应性并阐明 调节细胞命运和组织稳态以减轻疾病的机械转导机制 促进肌腱愈合。为了加速临床翻译，这个阿喀琉斯的总体目标是 肌腱病组织的核心是提供患者和临床相关的大鼠肌腱样本，范围从健康 退化，结合最完整的一套体内纵向检测，以最大限度地提高翻译 我们在P50申请中提出的研究项目的影响，以及NIH资助的许多项目 宾夕法尼亚大学旨在通过我们的P50调查团队改善肌腱愈合。在目标1中，我们将检索患者 组织学研究终末期跟腱病力学敏感性。在目标2中，我们将利用 肌腱病临床前模型研究疾病发病机制。这两个目标将使用广泛的电池 包括步态分析、负荷监测、关节力学、超声成像和 最大限度地将我们激动人心的研究项目转化为临床人群的研究成果。在……里面 目的3，我们将开发新的技术来转化临床前的发现，以改善患者的护理。这些 翻译工具是后续动物实验和临床试验所必需的，以测试其有效性 个性化康复护理在改善肌腱愈合和结果的同时解决现有的 对跟腱损伤患者的护理服务不公平。我们将加快基础发现 通过临床前研究向临床人群进行研究和翻译。通过建立阿喀琉斯 肌腱病组织核心，我们将提供独特严谨的技术和专业知识，以及细心 受控和特色化的研究材料提供给当地的肌腱研究人员，最终在全国范围内，同时 开发关键的新技术，以改善未来临床研究中的患者护理。我们选择了阿喀琉斯 肌腱病：在演示概念验证模型的同时解决一种常见且使人衰弱的疾病 利用患者组织和临床前模型的范例将加速基础发现 有效和公平的肌肉骨骼护理。

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.