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，肌腱的变性，导致肌腱病，被认为是由 机械过度使用。众所周知，肌腱病和肌腱病很难治疗，并且由于肌腱是一种主要的疾病， 运动器官，可能会使受影响的人身体虚弱。过度使用肌腱病的时间轴是 未完全阐明;关于急性过度使用和终末期慢性 肌腱病由于缺乏信息，目前的治疗方法在生理学上没有严格建立。在 为了评估结构和机械变化，使用新的多尺度成像模式， 机械测试是必要的。肌腱具有复杂的层次结构， 重塑发生在多个不同的长度尺度，使得多尺度分析是必要的。的目标 该建议是使用新的成像和多尺度机械测试与新的动物模型， 调查过度使用肌腱病的进展。将协同消融模型应用于超负荷大鼠 跖肌腱，并利用我的实验室在多尺度成像和机械测试的专业知识， 技术解决这个问题。 目的1：确定在肿瘤进展过程中体内发生的多尺度结构变化。 过度使用肌腱我假设肌腱的胶原纤维结构会改变， 结构和肌腱病变的大体病理学特征。在其余时间点， 我假设结构将继续恶化，尽管肌腱愈合可能 成功地能够逆转过度使用，并且可以评估愈合反应。 目的2：量化在体内发生的多尺度力学变化， 过度使用肌腱我推测，微尺度损伤将在4周时以 纤维之间不可恢复的滑动和增加的纤维应变。我还假设由于肌腱病 进展，分子胶原和微尺度纤维损伤将随后是受损的组织水平 力学性能 这项研究将建立在肌腱的结构和力学功能的进展过程中的关键变化 过度使用肌腱病了解这些变化将是向前迈出的重要一步， 这种普遍的肌肉骨骼疾病。作为一名有抱负的PI，我的职业目标是减轻 肌肉骨骼退化性损伤我在这个项目中接受的培训将使我成为一个有价值的 研究人员，精通复杂的机械测试，新型成像和图像分析， 临床前动物模型。特拉华州大学的埃利奥特实验室是一个活跃的、排名靠前的 网络的程序和教师集中在肌肉骨骼研究，是这个项目的理想选择。