Research Core

研究核心

• 批准号: 10403254
• 负责人: Josh Baxter
• 金额: $ 48.62万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403254
• 关键词: Acceleration; Acute; Address; Animal Experiments; Animals; Attenuated; Biological Assay; Caring; Cells; Center for Translational Science Activities; Chemicals; Chronic; Clinical; Clinical Research; Clinical Trials; Data Set; Disease; Disease Progression; Dose; Equity; Exercise; Funding; Future; Health; Homeostasis; Hospitals; Human; Inequity; Injections; Insurance Carriers; Intuition; Joints; Link; Mechanics; Medicine; Modeling; Monitor; Musculoskeletal; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Patient Care; Patient-Focused Outcomes; Patients; Physical therapy; Population; Pre-Clinical Model; Protocols documentation; Rattus; Regimen; Registries; Reporting; Research; Research Personnel; Research Project Grants; Rural Community; Sampling; Science; Techniques; Tendinopathy; Tendon Injuries; Tendon structure; Testing; Therapeutic Agents; Tissues; Translating; Translational Research; Translations; Ultrasonography; United States National Institutes of Health; Urban Community; achilles tendon; care delivery; clinical translation; clinically relevant; cost; early onset; effectiveness testing; follow-up; fundamental research; gait examination; healing; human tissue; improved; in vivo; innovation; mechanical load; metabolomics; new technology; novel; pain symptom; patient population; pre-clinical; pre-clinical research; preclinical study; rehabilitative care; research study; suburban communities; tendon rupture; therapeutic effectiveness; tool; translation assay; translational impact; ultrasound

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.

研究核心摘要 跟腱病是一种疼痛，衰弱，慢性肌腱条件。患者接受物理治疗 作为保守治疗的第一步。这些物理治疗协议是唯一的非- 由大多数保险公司支付的外科治疗-规定机械负荷作为治疗剂。然而，在这方面， 60%的患者在5年后继续报告疼痛症状，50%的患者寻求 保守治疗失败后手术治疗。因此，最大化的治疗效果， 机械负荷对于改善患者的治疗效果和减少昂贵且经常需要的 无效的手术治疗。为了满足这一未满足的临床需求，我们建议的研究项目将建立 肌腱细胞的机械反应性在整个肌腱病变疾病的进展，并阐明 调节细胞命运和组织稳态以减轻疾病的机械传导机制 促进肌腱愈合。为了加速临床转化，这一阿基里斯的总体目标是 Tendinopathy Tissue Core旨在提供患者和临床相关的大鼠肌腱样本，范围从健康的 结合最完整的一套纵向体内试验，以最大限度地提高翻译效率。 我们在这个P50申请中提出的研究项目的影响，以及许多NIH资助的项目， Penn旨在通过我们的P50研究团队改善肌腱愈合。在目标1中，我们将检索患者 组织研究终末期跟腱病机械敏感性。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。这两个目标将利用广泛的电池 包括步态分析、负荷监测、关节力学、超声成像和 代谢组学，以最大限度地从我们令人兴奋的研究项目，临床人群的研究翻译。在 目标3，我们将开发新的技术来转化临床前发现，以改善患者护理。这些 翻译工具是必要的后续动物实验和临床试验，将测试的有效性 个性化康复护理，改善肌腱愈合和结果，同时解决现有的 对跟腱损伤患者的不公平护理。我们将加速基础发现 通过临床前研究转化为临床人群。通过建立阿基里斯 肌腱病组织核心，我们将提供独特而严谨的技术和专业知识，以及精心 控制和表征的研究材料，以肌腱研究人员在当地，并最终在全国范围内，而 开发关键的新技术，以改善未来临床研究中的患者护理。我们选择了阿基里斯 肌腱病，以解决一个常见的和衰弱的条件，同时证明了概念验证模型 利用患者组织与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。