组织工程支架不仅为细胞的分化和移行提供附着和支撑功能，近期研究显示支架的物理特性还会明显影响干细胞的分化。本实验组前期的研究发现，细胞外基质的排列显著影响了干细胞的腱系和骨系分化，并且与整合素有关（Biomaterials 2010）。因此，本课题在此基础上进一步研究细胞结构性微环境（支架微细排列和硬度）对整合素的作用，结合BMP受体通过脂筏内吞参与调控Smad亚型的选择性激活或抑制，诱导肌腱干细胞的特异性分化。本研究拟结合现有的干细胞生物学、材料工程学和组织工程学手段，探索细胞外结构性微环境刺激对于肌腱干细胞自我更新和分化的效应，以及integrin-BMP-Smad通路如何参与物理特性诱导细胞分化的调控机制。预期本研究发现将进一步阐明细胞外基质调控腱系分化的分子机制，并为肌腱组织诱导性的功能支架的设计提供实验基础和全新的思路。

Recent studies reveals that the topography and rigidity of the extracellular microenvironment plays an important role in cellular activity, from attachment and morphology to proliferation and differentiation though contact guidance. The effect and mechanism of bioscaffold provided structure niche on tendon stem cell differentiation has not been investigated. The new materials-based approach aims to control stem cell behavior by mimicking the characteristics of natural ECMs. This program based on our pilot studies about interaction between stem cell and biomaterials, aimed to develop a biomimetic scaffold for tendon differentiation and tissue engineering. Firstly, we will determine the effects of different nanotopography and rigidity on the differentiation of tendon stem cells (TSCs) in vitro, in order to optimize the proper structure niche for tenogenesis. Secondly, how does the integrin mediated mechanotransduction pathway participate in the matrix-determined differentiation will be clarified, especially the BMP-Smad signaling pathway. We try to explore the structure niche effect on the integrin-beta1 and BMPR, which could inhibit bone differentiation. Then, in vivo experiment will be preformed to evaluate the utility and efficacy of bioscaffold physical signal on tendon repair. In conclusion, this study focus on investigating ideal scaffold properties, which provides an instructive microenvironment for stem cell differentiation to teno-lineage, and exploring the mechanism of matrix-induced stem cell commitment in order to lead to the development of desirable engineered tendons.