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Research Core

研究核心

基本信息

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
项目类别：
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

项目摘要

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.

研究核心总结跟腱病是一种疼痛、使人衰弱的慢性肌腱疾病。患者接受物理治疗治疗作为保守治疗的第一步。这些物理治疗方案——这是唯一的非大多数保险公司支付手术治疗费用——规定机械负荷作为治疗剂。然而，百分之六十的患者在 5 年后仍报告疼痛症状，百分之五十的患者寻求治疗保守治疗无效后进行手术治疗。因此，最大限度地提高治疗效果机械负荷对于改善患者治疗效果和减少昂贵且频繁的手术需求至关重要手术治疗无效。为了满足这一未满足的临床需求，我们提议的研究项目将建立肌腱细胞在整个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传导机制进展并改善肌腱愈合。为了加速临床转化，这个 Achilles 的总体目标肌腱病组织核心旨在提供患者和临床相关的大鼠肌腱样本，范围从健康与最完整的纵向体内测定相结合，以最大化转化我们在此 P50 申请中提出的研究项目以及 NIH 资助的众多项目的影响 Penn 的 P50 研究团队旨在改善肌腱愈合。在目标 1 中，我们将救回患者组织来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 2 个目标将使用大量电池体内分析，包括步态分析、负荷监测、关节力学、超声成像和代谢组学，最大限度地提高从我们令人兴奋的研究项目到临床人群的研究转化。在目标 3，我们将开发新技术来转化临床前研究结果，以改善患者护理。这些后续动物实验和临床试验需要转化工具来测试有效性个性化康复护理可改善肌腱愈合和结果，同时解决现有问题跟腱损伤患者的护理服务不公平。我们将加速基础发现通过临床前研究向临床人群进行研究和转化。通过建立阿喀琉斯肌腱病组织核心，我们将提供独特而严谨的技术和专业知识，以及精心向当地并最终全国范围内的肌腱研究人员提供控制和表征的研究材料，同时开发关键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可解决一种常见且令人衰弱的疾病，同时演示概念验证模型利用临床前模型的患者组织将加速基础发现有效和公平的肌肉骨骼护理。