细胞基质化组织工程神经修复神经缺损及神经再生微环境重建的机制研究

组织工程是多学科交叉的前沿领域，组织工程新技术新产品研发正面对着国际国内巨大的市场需求。本课题在20余年研究工作积累的基础上创新性提出：①采用皮肤前体细胞，诱导分化成施万细胞，将丝素与施万细胞体外构建组织工程神经，化学方法去细胞，制备细胞基质化组织工程神经；②将细胞基质化组织工程神经修复大鼠坐骨神经缺损，制备动物模型；③利用RNA深度测序分析方法揭示再生神经组织微环境转录水平的变化，通过IPA等生物信息学分析工具系统分析其差异基因表达、核心调控因子、信号通路及其分子调控机制；④关键因子验证，并进行体外水平与动物体内功能验证与分析。为细胞基质化组织工程神经修复神经缺损与神经再生微环境重建及其人工组织与机体微环境相互作用的机制研究提供新的知识与新的理论。

Tissue engineering is an advanced multidisciplinary field. The investigation and development of new tissue engineering technology and product is facing huge international and domestic market demand. Based on more than 20 years’ research experiences, the current project innovatively proposed: ① inducing skin precursor cells to differentiate into Schwann cells, using silk fibronin and Schwann cells to construct tissue engineering nerve, decellularized by using chemical methods, and construct cellular extracellular matrix based-tissue engineering nerve; ② using cellular extracellular matrix based-tissue engineering nerve to repair rat sciatic nerve transection, prepare animal model；③ using RNA deep sequencing to discover the changes of the microenviroment of regenerated nerve tissue from the transcriptional level, using bioinformatic analysis tools (e.g. IPA) to analyze the expression patterns of differentially expressed genes, core transcriptional factors, signaling pathways and molecular regulatory mechanism；④ validating key factors, use in vitro and in vivo experiments to perform functional verification and analysis. The current project will provide new knowledge and theory for nerve repair and regenerative microenviroment reconstruction with cellular extracellular matrix based-tissue engineering nerve and the interaction of artificial tissue and body microenvironment.