John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Sci Robot. 2023 Mar 22;8(76):eadd9369. doi: 10.1126/scirobotics.add9369.
Robot-actuated mechanical loading (ML)-based therapies ("mechanotherapies") can promote regeneration after severe skeletal muscle injury, but the effectiveness of such approaches during aging is unknown and may be influenced by age-associated decline in the healing capacity of skeletal muscle. To address this knowledge gap, this work used a noninvasive, load-controlled robotic device to impose highly defined tissue stresses to evaluate the age dependence of ML on muscle repair after injury. The response of injured muscle to robot-actuated cyclic compressive loading was found to be age sensitive, revealing not only a lack of reparative benefit of ML on injured aged muscles but also exacerbation of tissue inflammation. ML alone also disrupted the normal regenerative processes of aged muscle stem cells. However, these negative effects could be reversed by introducing anti-inflammatory therapy alongside ML application, leading to enhanced skeletal muscle regeneration even in aged mice.
机器人驱动的机械加载（ML）为基础的治疗（“机械疗法”）可以促进严重的骨骼肌损伤后的再生，但这种方法在衰老过程中的有效性尚不清楚，并且可能受到与年龄相关的骨骼肌愈合能力下降的影响。为了填补这一知识空白，本研究使用一种非侵入性、负载控制的机器人设备施加高度定义的组织应力，以评估 ML 在损伤后肌肉修复中的年龄依赖性。结果发现，受伤肌肉对机器人驱动的循环压缩加载的反应具有年龄敏感性，不仅表明 ML 对受伤的老年肌肉没有修复益处，而且还加剧了组织炎症。单独的 ML 也破坏了老年肌肉干细胞的正常再生过程。然而，通过在 ML 应用的同时引入抗炎治疗，可以逆转这些负面影响，即使在老年小鼠中也能增强骨骼肌再生。
