Novel model of tendinosis to investigate multiscale structure and function of tendon after overload

研究超负荷后肌腱多尺度结构和功能的新型肌腱变性模型

• 批准号: 10477954
• 负责人: Ellen Bloom
• 金额: $ 4.1万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-20 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477954
• 关键词: 3-Dimensional; Ablation; Acute; Address; Affect; Animal Model; Animals; Area; Biological; Biological Assay; Caliber; Characteristics; Chronic; Clinical; Collagen; Collagen Fiber; Collagen Fibril; Cumulative Trauma Disorders; Custom; Data; Delaware; Development; Devices; Diagnosis; Disease; Excision; Face; Faculty; Fiber; Generations; Goals; Histologic; Human; Hybrids; Hypertrophy; Image; Image Analysis; Impairment; Injury; Intervention; Knowledge; Length; Magnetic Resonance Imaging; Measures; Mechanics; Methods; Modeling; Modulus; Molecular; Movement; Muscle; Musculoskeletal; Musculoskeletal Diseases; Organ; Pain; Pathologic; Peptides; Physiological; Physiology; Rattus; Research; Research Personnel; Rest; Scanning Electron Microscopy; Slide; Structure; System; Techniques; Tendinopathy; Tendon structure; Testing; Time; TimeLine; Tissues; Training; Universities; Work; achilles tendon; career; density; healing; high throughput analysis; in vivo; innovation; mechanical properties; molecular scale; nanoscale; novel; novel imaging technique; pre-clinical; programs; research clinical testing; response; second harmonic

Project Summary Chronic tendinosis, the degeneration of tendon which leads to tendinopathy, is believed to be initiated by mechanical overuse. Tendinosis and tendinopathy are notoriously difficult to treat, and as tendon is a major organ of movement, can be physically debilitating to those affected. The timeline of overuse tendinopathy is not fully elucidated; there is limited work on the progression between acute overuse and end-stage chronic tendinopathy. Current treatments are not rigorously established in physiology due to this lack of information. In order to evaluate the structural and mechanical changes, the use of novel multiscale modes of imaging and mechanical testing is necessary. Tendon has a complicated hierarchical structure, with damage and remodeling occur at multiple different length scales, making multiscale analysis necessary. The objective of this proposal is to use novel imaging and multiscale mechanical testing with a novel animal model to investigate the progression of overuse tendinosis. I will apply the synergistic ablation model to overload rat plantaris tendon and use my lab’s expertise in multiscale imaging and mechanical testing to apply novel techniques to this problem. Aim 1: Determine the multiscale structural changes occurring in vivo during the progression of overuse tendinosis. I hypothesize that tendon will show altered collagen fibril structure, altered collagen fiber structure, and gross pathological hallmarks of tendinopathy by 4 weeks. Throughout the rest of the time points, I hypothesize that structure will continue to deteriorate, though it is possible that tendon healing may successfully be able to reverse overuse, and the healing response may be evaluated. Aim 2: Quantify the multiscale mechanical changes occurring in vivo during the progression of overuse tendinosis. I hypothesize that microscale damage will initiate at 4 weeks in the form of nonrecoverable sliding between fibers and increased fiber strain. I also hypothesize that as tendinosis progression, molecular collagen and microscale fiber damage will be followed by impaired tissue-level mechanical properties. This study will establish key changes in the structure and mechanical function of tendon during the progression of overuse tendinopathy. Understanding these changes will be an important step forward in being able to treat this prevalent musculoskeletal disorder. My career goals as an aspiring PI are to reduce the burden of musculoskeletal degenerative injuries. The training I will receive during this project will make me a valuable investigator, with proficiencies in sophisticated mechanical testing, novel imaging and image analysis, and preclinical animal models. The Elliott Lab at the University of Delaware is part of an active and highly ranked network of programs and faculty centered on musculoskeletal research, and is ideal for this project.

项目摘要 慢性肌腱病是导致肌腱病的肌腱的变性，被认为是由 机械过度使用。肌腱病和肌腱病很难治疗，因为肌腱是主要的 运动器官可以使受影响的人身体上衰弱。过度使用肌腱病的时间表是 未完全阐明；急性过度使用和终末期慢性之间的进展工作有限 肌腱病。由于缺乏信息，目前的治疗在生理学中并未严格确定。在 为了评估结构和机械变化，新型多尺度成像模式的使用 和机械测试是必要的。肌腱具有复杂的层次结构，损坏和 重塑发生在多个不同的长度尺度上，因此需要多尺度分析。目的 该建议是使用新颖的动物模型使用新颖的成像和多尺度机械测试来 研究过度使用肌腱病的进展。我将应用协同消融模型来超负荷大鼠 Plantaris肌腱，并使用我的实验室在多尺度成像和机械测试方面的专业知识应用新颖 解决这个问题的技术。 目标1：确定在体内发生的多尺度结构变化。 过度使用肌腱病。我假设肌腱会显示出改变的胶原纤维结构，胶原蛋白纤维改变 肌腱病的结构和严重的病理标志，征收4周。在剩下的时间点， 我假设该结构将继续确定，尽管肌腱愈合可能可能 能够成功地过度使用，并可以评估愈合反应。 目标2：量化多尺度机械变化在体内发生 过度使用肌腱病。我假设微观损伤将在4周以 在纤维和增加的纤维应变之间不可偿还的滑动。我还假设这是肌腱病 进展，分子胶原蛋白和微观纤维损伤将受损组织级 机械性能。 这项研究将在进展过程中建立肌腱结构和机械功能的关键变化 过度使用肌腱病。了解这些变化将是能够对待的重要一步 这种普遍的肌肉骨骼疾病。我作为有抱负的PI的职业目标是减少燃烧 肌肉骨骼退行性损伤。在这个项目中我将接受的培训将使我有价值 研究人员，具有复杂的机械测试，新型成像和图像分析以及 临床前动物模型。特拉华大学的埃利奥特实验室是活跃且排名较高的一部分 计划和教师网络以肌肉骨骼研究为中心，是该项目的理想选择。