A Multiscale Investigation of Fatigue Induced Damage Progression in Tendon

肌腱是一种承重组织，在其寿命期内承受数百万次循环。这些强烈的循环负荷可能导致伤害。这项研究将奠定基础，了解复杂性恶化的结构完整性，由于重复加载的钢筋束。肌腱是一种生物材料，具有跨越几个长度尺度的分层“构建块”。因此，重要的是要了解每个尺度下疲劳载荷引起的机械性能和退化。这项工作将使用多尺度实验，计算建模和多尺度模拟的进展来揭示组织的结构损伤如何影响负责组织修复的肌腱细胞的微环境。 揭示肌腱对重复载荷的非凡弹性的机制也将指导下一代工程软材料的设计。这个项目将包括来自代表性不足的群体的学生的贡献，包括本科生，并将有助于夏季外展计划。这项工作将探索多尺度肌腱力学与一系列明确定义的目标，即：1）表征胶原纤维的微观疲劳响应和损伤，2）开发疲劳诱导损伤的宏观模型，和3）鉴定改变腱细胞微环境的损伤诱导的多尺度结构改变。 缺乏对肌腱疲劳引起的多尺度损伤进展的基本理解和预测能力，限制了其他基础研究的进展，包括细胞力学、转化研究和机械信息疗法的发展。在理解循环载荷过程中肌腱的可塑性分级级联以及它与肌腱损伤的关系方面仍然存在很大的差距。 从胶原原纤维实验和粗粒度分子动力学模拟在相同的规模开始，这项工作将开发宏观理论和模型的肌腱，将能够捕捉到拉伸疲劳载荷的响应，包括损伤的启动和失败。为了便于在连续体水平的预测，在有限变形的损伤和塑性有限元框架将开发和模拟结果校准宏观（肌腱级）疲劳载荷实验。这项工作有可能为疲劳引起的肌腱损伤提供机制性的理解，揭示肌腱细胞微环境的改变如何驱动愈合，并提供预测能力，最终为肌腱病的运动治疗提供信息。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

Tendon is a load-bearing tissue that is loaded through millions of cycles over a lifespan. These intense cyclic loads can lead to injury. This study will lay the groundwork for understanding the complexities in deteriorating structural integrity of tendon due to repeated loading. Tendon is a biological material with hierarchical “building blocks” that span several length scales. Therefore, it is important to understand the mechanical behavior and degradation due to fatigue loading at each scale. This work will use experiments at multiple scales, computational modeling, and advances in multiscale simulations to reveal how structural damage of the tissue affects the micro-environment of the tendon cells responsible for the repair of the tissue. Uncovering the mechanisms underlying tendon’s remarkable resilience to repeated loading will also guide the design of next generation engineered soft materials. This project will include contributions from students from underrepresented groups, including undergraduate students, and will contribute to summer outreach programs.This work will probe multiscale tendon mechanics with a series of clearly defined objectives, namely: 1) characterizing microscale fatigue response and damage of collagen fibrils, 2) developing a macroscopic model for fatigue induced damage, and 3) identifying damage-induced multiscale structural alterations that modify the tenocyte micro-environment. The absence of basic understanding and predictive capabilities for fatigue induced multiscale damage progression in tendon limits the progress of other basic studies including cell mechanics, translational studies, and development of mechanistically informed therapeutics. There is still a substantial gap in understanding the hierarchical cascade of plasticity in tendon during cyclic loading and how it correlates with tendon damage. Starting from collagen fibril experiments and coarse-grained molecular dynamics simulations at the same scale, this work will develop macroscopic theories and models for tendon that will be able to capture the response to tensile fatigue loading including damage initiation and failure. To facilitate predictions at the continuum level, a finite element framework for damage and plasticity at finite deformation will be developed and the simulation results calibrated against macroscopic (tendon-level) experiments for fatigue loading. This work has the potential to provide mechanistic understanding for fatigue induced tendon damage, uncover how alterations to the tenocyte micro-environment drive healing, and provide predictive capabilities that will ultimately inform exercise based treatments to tendinopathy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.