A Multiscale Investigation of Fatigue Induced Damage Progression in Tendon

肌腱是一种承重组织，在一生中经历数百万个循环。这些剧烈的循环负荷可能会导致受伤。这项研究将为理解由于重复加载而导致肌腱结构完整性恶化的复杂性奠定基础。肌腱是一种生物材料，具有跨越几个长度尺度的分级“积木”。因此，了解疲劳载荷在每个尺度下的力学行为和退化是很重要的。这项工作将利用多尺度的实验、计算模型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。揭示肌腱对重复加载的非凡弹性背后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不足群体的学生的贡献，包括本科生，并将有助于暑期外展计划。这项工作将探索多尺度肌腱力学，具有一系列明确的目标，即：1)表征微观尺度的疲劳反应和胶原纤维的损伤，2)建立疲劳诱导的损伤的宏观模型，以及3)识别损伤引起的改变腱细胞微环境的多尺度结构改变。缺乏对疲劳引起的肌腱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、翻译研究和机械信息疗法的发展。在理解肌腱在循环加载过程中塑性的分级级联以及它与肌腱损伤的相关性方面，仍有很大的差距。从胶原原纤维实验和相同尺度的粗粒分子动力学模拟出发，本工作将发展肌腱的宏观理论和模型，能够捕捉拉伸疲劳载荷的响应，包括损伤起始和破坏。为了便于在连续体水平上进行预测，将建立有限变形下损伤和塑性的有限元框架，并将模拟结果与疲劳加载的宏观(肌腱水平)实验进行校准。这项工作有可能为疲劳引起的肌腱损伤提供机械上的理解，揭示腱细胞微环境的变化如何推动愈合，并提供预测能力，最终为肌腱疾病的基于运动的治疗提供信息。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.