Multiscale Computational Tool to Reduce the Prevalence of Age-Related Tendinopathy by Resolving the Key Mechanisms of Tendon Dynamics

多尺度计算工具通过解决以下问题来降低年龄相关性肌腱病的患病率 肌腱动力学的关键机制 项目摘要 这项工作的长期目标是改变年龄相关性肌腱病的临床范例，并合理地 通过确定肌腱的关键机制来设计防止退变和促进愈合的策略 伤情前后的动态变化。年龄相关性肌腱病是一种身体虚弱和疼痛的疾病。 其中肌腱结构完整性和力学性能下降，增加断裂风险。现有 治疗往往无法恢复肌腱的力量和功能，从而导致巨大的医疗成本和 对高达三分之一的50岁以上成年人的生活质量产生负面影响。然而，关键的机制是 与年龄相关的肌腱变化和愈合缺陷还没有被很好地理解。我们试图确定关键 肌腱动力学机制的研究可有效聚焦临床干预。为了实现这一目标，我们建议 利用一种计算工具，通过小鼠膝盖腱的实验数据来了解和验证 找出随年龄增长动态平衡的维持和恢复的关键机制。 我们的中心假设是，肌腱细胞通过产生或移除负重来对日常运动做出反应 肌腱成分，维持内环境平衡状态。此外，我们假设与年龄相关的干扰会 这些成分的生产和去除的平衡增加了对退化和/或 通过降低机械性能和愈合潜力而撕裂。在本提案的目标1中，我们将评估 肌腱机械动态平衡对不同递减生产机制的年龄敏感性。在……里面 目的2，我们将通过评估改变的效果来确定肌腱生长潜力的年龄界限。 动态平衡的机械负荷。在目标3中，我们将描述特定年龄的肌腱组件 阻碍损伤后机械内稳态恢复的适应。成功完成 这项研究将为肌腱动力学的关键机制提供一个基本的理解。 年龄越来越大。此外，它将为预测计算模型的发展迈出重要的一步 帮助合理设计针对患者的治疗计划和干预措施，改善患者的临床护理 年龄相关性肌腱病。

Multiscale Computational Tool to Reduce the Prevalence of Age-Related Tendinopathy by Resolving the Key Mechanisms of Tendon Dynamics Project Summary The long term goal of this work is to alter the clinical paradigm for age-related tendinopathy and to rationally design strategies to impede degeneration and improve healing by identifying the key mechanisms of tendon dynamics before and after injury. Age-related tendinopathy is a physically debilitating and painful disorder wherein tendon structural integrity and mechanical performance decline, increasing the risk of rupture. Existing treatments often fail to restore tendon strength and functionality, contributing to significant healthcare costs and negatively impacting quality of life for up to one in three adults over fifty. Nevertheless, the key mechanisms of age-related tendon changes and healing deficiencies are not well-understood. We seek to determine the key mechanisms of tendon dynamics to effectively focus clinical intervention. To accomplish this we propose to leverage a computational tool, informed and validated by experimental data in the murine patellar tendon, to identify the key mechanisms that diminish the preservation and restoration of dynamic homeostasis with age. Our central hypothesis is that tendon cells respond to daily motions by producing or removing load-bearing tendon components to maintain a homeostatic state. Further, we hypothesize that age-related disruptions to the balance of the production and removal of these components increase susceptibility to degeneration and/or tears by decreasing mechanical performance and healing potential. In Aim 1 of this proposal, we will evaluate the age-specific sensitivity of tendon mechanical homeostasis to different declining production mechanisms. In Aim 2, we will determine the age-specific bounds of tendon growth potential by evaluating the effect of altered mechanical loading on homeostasis. In Aim 3, we will delineate the age-specific tendon component adaptations which hinder the restoration of mechanical homeostasis following injury. Successful completion of this study will provide a fundamental understanding of the critical mechanisms of tendon dynamics with increasing age. Further, it will provide a vital step towards the development of predictive computational models to aid in the rational design of patient-specific treatment plans and interventions, improving the clinical care of age-related tendinopathy.