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肌腱动力学的关键机制来减少与年龄相关的肌腱病的患病率

• 批准号: 9353033
• 负责人: Kristin Suzanne Miller
• 金额: $ 26.13万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9353033
• 关键词: Adult; Affect; Age; Aging; Arteries; Atrophic; Biological; Biological Preservation; Blood Vessels; Cells; Centers of Research Excellence; Clinical; Collagen; Collagen Fiber; Computer Simulation; Core Facility; Data; Deposition; Development; Disease; Elastic Fiber; Elderly; Equilibrium; Etiology; Excision; Fibrosis; Functional disorder; Geometry; Goals; Growth; Health Care Costs; Homeostasis; Incidence; Individual; Injury; Intervention; Lead; Maintenance; Mechanical Stress; Mechanics; Mentors; Modeling; Motion; Mus; Musculoskeletal; Natural regeneration; Orthopedics; Pain; Pathology; Pathway interactions; Patients; Performance; Predisposition; Prevalence; Process; Production; Property; Proteins; Quality of life; Regenerative Medicine; Research; Risk; Rupture; Stimulus; Structure-Activity Relationship; Tendinopathy; Tendon structure; Testing; Therapeutic Intervention; Tissues; Weight-Bearing state; Work; age related; clinical care; computerized tools; design; experience; healing; improved; mechanical load; mechanical properties; mouse model; patellar tendon; research facility; response; restoration; tendon development; therapy design; treatment planning

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.

多尺度计算工具通过解决以下问题来降低肌腱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模式， 设计策略，通过识别肌腱的关键机制来阻止退化并改善愈合 受伤前后的动态肌腱相关的肌腱病是一种身体衰弱和痛苦的疾病 其中肌腱结构完整性和机械性能下降，增加了断裂的风险。现有 治疗通常不能恢复肌腱的强度和功能，导致显著的医疗保健成本， 对三分之一的50岁以上成年人的生活质量产生负面影响。然而， 与年龄相关的肌腱变化和愈合缺陷还没有得到很好的理解。我们试图找出 肌腱动力学机制，以有效地集中临床干预。为了实现这一目标，我们建议 利用一种计算工具，通过小鼠髌腱的实验数据得到信息和验证， 确定随着年龄的增长而减少动态平衡的保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承重细胞来响应日常运动。 肌腱组件来维持体内平衡状态。此外，我们假设年龄相关的干扰， 这些组分的产生和去除的平衡增加了对变性的敏感性和/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 肌腱机械稳态对不同产量下降机制的年龄特异性敏感性。在 目的2，我们将通过评估改变的影响来确定肌腱生长潜力的年龄特异性界限。 机械负荷对体内平衡的影响在目标3中，我们将描述特定年龄的肌腱成分 损伤后阻碍机械稳态恢复的适应。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， 年龄增长。此外，它将为预测计算模型的发展迈出重要的一步 帮助合理设计患者特定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