Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
J Biomech. 2019 Mar 6;85:148-156. doi: 10.1016/j.jbiomech.2019.01.026. Epub 2019 Jan 19.
Tendinopathies are common chronic injuries that occur when damage accumulation caused by sub-rupture fatigue loading outpaces repair. Studies have linked fatigue loading with various mechanical, structural, and biological changes associated with pathology. However, the multiscale progression of damage accumulation with respect to area, severity and the distinct contributions of strain level and number of cycles has not been fully elucidated. The objective of this study was to investigate multiscale mechanisms underlying fatigue damage accumulation and their effect on the cellular environment. Using an in situ model in rat tail tendon (RTT), fatigue loading was applied at various strains and cycle numbers to induce fatigue damage. Pre- and post- fatigue diagnostic mechanical testing, second harmonic generation (SHG) imaging, and transmission electron microscope (TEM) imaging were used to investigate extracellular and cellular damage modes at multiple scales. Fatigue loading at strains at or below 1.0% resulted in no significant changes in SHG damage area or severity and no changes in collagen fibril or cell morphology compared with controls. Fatigue loading at strains above 1.5% resulted in greater mechanical changes correlated with increased damage area measured by SHG and collagenous damage observed by TEM. Increased cycles at high strain further altered mechanical properties, increased structural damage severity (but not area), and altered TEM collagen rupture patterns. Cell morphology was similarly progressively affected with increased strain and cycle number. These damage mechanisms that may trigger degenerative changes characteristic of tendinopathy could be targeted as a part of prevention or therapy.
腱病是常见的慢性损伤，当亚破裂疲劳负荷引起的损伤积累超过修复能力时就会发生。研究已经将疲劳负荷与各种与病理学相关的机械、结构和生物学变化联系起来。然而，损伤积累的多尺度进展，包括面积、严重程度以及应变水平和循环次数的独特贡献，尚未得到充分阐明。本研究的目的是探讨疲劳损伤积累的多尺度机制及其对细胞环境的影响。使用大鼠尾腱（RTT）的原位模型，在不同的应变和循环次数下施加疲劳负荷以诱导疲劳损伤。在疲劳前后进行诊断性机械测试、二次谐波产生（SHG）成像和透射电子显微镜（TEM）成像，以研究多个尺度上的细胞外和细胞损伤模式。与对照组相比，在 1.0%或以下的应变下进行疲劳加载不会导致 SHG 损伤面积或严重程度的显著变化，也不会导致胶原纤维或细胞形态的变化。在 1.5%以上的应变下进行疲劳加载会导致更大的机械变化，这与通过 SHG 测量的损伤面积增加以及 TEM 观察到的胶原损伤增加有关。在高应变下增加循环次数会进一步改变机械性能、增加结构损伤严重程度（但不增加面积），并改变 TEM 胶原断裂模式。细胞形态也随着应变和循环次数的增加而逐渐受到影响。这些可能引发腱病特征性退行性变化的损伤机制，可以作为预防或治疗的一部分进行靶向治疗。
