肌腱病是最常见的软组织疾病之一，钙化性肌腱病为其中严重的亚型，而关键的发病机理尚不明确且临床缺乏长期有效的治疗方法。我们前期发现其病理过程主要为内源性肌腱干/祖细胞在疾病微环境下异常分化，发生异位骨软骨分化并最终进展为钙化（Stem Cells 2015）。进一步实验发现肌腱组织特异mTOR基因敲除可显著抑制肌腱干/祖细胞分化（Stem Cells 2018），减少肌腱异位成骨，深入分析发现与组蛋白乙酰化修饰水平相关。因此，我们假说肌腱病中mTOR通过调控肌腱干/祖细胞的组蛋白修饰诱导肌腱异位骨化。本课题拟阐明mTOR在肌腱病钙化中的作用及机制，并针对肌腱致密及寡血管导致的给药困难等特点，结合材料工程学手段，利用纳米缓释材料和可特异结合损伤胶原的胶原杂交肽CHP，靶向缓释药物雷帕霉素，实现损伤肌腱靶向给药和缓释性能。预期本研究将为肌腱钙化的治疗提供新知识和治疗新技术。

Tendinopathy is one of the most common soft tissue diseases, among which calcified tendinopathy is one of the most serious subtypes. However, the pathological mechanism is still unclear and there is no long-term effective treatment in clinic. Previously, we confirmed that the main pathological process was attributed to the abnormal differentiation of endogenous tendon stem/progenitor cells (TSPCs) in the microenvironment of disease, following by formation of heterotopic ossification and calcification which severely undermined the structure of tendon tissue. Our further experiments showed that mTOR gene knockout could significantly inhibit the differentiation of TSPCs and reduce tendon heterotopic ossification. And this bioprocess was found to be related to the acetylation modification level of histone. Therefore, we hypothesize that mTOR induces tendon heterotopic ossification in tendinopathy by regulating histone modification of TSPCs. The purpose of this study is to elucidate the role and mechanism of mTOR in tendon calcification. In view of the characteristics of tendon including denseness and avascularity, it is hard to deliver drugs to tendon. In this study, combining material engineering technology, we develop a nano-sustained-release material modified with collagen hybridizing peptide (CHP), which can specifically bind to damaged collagen, to targeting deliver and sustain-release drug rapamycin into diseased tendon. It is expected that our study will provide a new theory and a new technology for the treatment of tendon calcification.