生物医用材料表面的拓扑结构调控间充质干细胞免疫属性的效应及机制研究

项目名称： 生物医用材料表面的拓扑结构调控间充质干细胞免疫属性的效应及机制研究

项目编号： No.31470948

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 柳华

作者单位： 浙江大学

项目金额： 90万元

中文摘要： 材料与机体的相互作用影响材料的生物效应。研究显示生物材料成分和拓扑结构影响机体免疫细胞和反应,但尚无研究报道材料对非免疫细胞如间充质干细胞（MSC）的免疫属性的调控。我们前期研究提示MSC的免疫属性决定其移植后的存活和生物性能（J Immuno.2006; J Cell Sci.2012）,近期我们预实验发现无序纳米纤维表面拓扑结构可诱导MSC合成促炎症因子。因此我们假说生物材料表面拓扑结构调控MSC的免疫属性。本研究1）拟用流式细胞检测法及多重荧光分析法检测体外生物材料表面拓扑结构对MSC相关免疫分子的调控及诱导的免疫反应亚型，2) 用扫描离子电导显微镜及多基因分析的手段探索材料拓扑结构引起MSC表面分子排列的改变、继而诱导细胞内信号传导途径的变化机制，3) 采用体内组织缺损模型验证这些改变对组织修复的影响。明确这些效应及机制对组织工程化支架产品的设计和改造具有重要的参考和指导意义。

中文关键词： 组织工程；生物相容性；骨髓间充质干细胞；微环境

英文摘要： The therapeutic efficacy of biomedical materials is largely determined by their interaction with the human body. Several studies have shown that both the chemical constitution and surface topography of biomedical materials significantly affect the interaction of these materials with the immune system, but there is little available data about their effects on the immunological properties of mesenchymal stem cells (MSC). Based on our previous research (J Immuno. 2006; J Cell Sci., 2012), the immunological properties of MSC determine their survival and therapeutic efficacy after implantation. Moreover, our preliminary data showed that random surface topography of biomedical materials can induce the synthesis of pro-inflammatory factors by MSC. Therefore, we hypothesized that the surface topography of biomedical materials can significantly affect the immunological properties of MSC. Hence, our proposed research would investigate 1) the alteration of immune marker expression and cytokine secretion profile of MSCs with flow cytometry analysis and multiplex assay; 2) the effects of combining different surface molecules with varying surface topography on the immune signalling pathways of MSC, using scanning ion conductance microscopy and multi-gene expression analysis; 3) the regenerative potential of these various MSC-biomaterial composites of different surface topography upon implantation in vivo. The results obtained can facilitate the redesign and retrofit of existing biomedical materials.

英文关键词： tissue engineering;biomaterials;topography;mesenchymal stem cells