Chainani Pooja H, Buzo Mena Maria, Yeritsyan Diana, Caro Daniela, Momenzadeh Kaveh, Galloway Jenna L, DeAngelis Joseph P, Ramappa Arun J, Nazarian Ara
Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Department of Mechanical Engineering, Boston University, Boston, MA, United States.
Front Bioeng Biotechnol. 2024 Mar 7;12:1327094. doi: 10.3389/fbioe.2024.1327094. eCollection 2024.
Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Here, we show that fatigue overloading significantly reduces functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.
肌腱病是一种退行性疾病，是由于肌腱长期经历异常程度的多尺度损伤，损害了其修复能力所致。然而，由于该疾病主要以终末期临床表型为特征，与肌腱病起始相关的损伤标志物尚不清楚。因此，本研究旨在使用体内被动踝关节背屈系统评估肌腱对连续疲劳性肌腱过载发作的急性反应。将Sprague Dawley雌性大鼠的跟腱进行1次、2次或3次疲劳过载，每次发作之间休息两天。对肌腱样本进行力学、结构和生物学检测，以评估对过载损伤的固有急性愈合反应。在此，我们表明疲劳过载显著降低了功能和力学性能，滞后、峰值应力以及加载和卸载模量均降低。细胞、原纤维和纤维水平的多尺度结构损伤表明存在累积的微损伤，这可能引发了对连续加载发作的修复反应。急性愈合反应导致基质更新改变以及与基质重塑和损伤急性反应相关的早期炎症上调。这项工作证明了连续疲劳过载发作导致的累积损伤和肌腱愈合反应的急性变化。这些结果为未来在肌腱病背景下对肌腱过载进行长期评估的研究提供了途径。
