细胞外基质修饰的组织工程神经移植物修复周围神经缺损的研究

项目名称： 细胞外基质修饰的组织工程神经移植物修复周围神经缺损的研究

项目编号： No.81471255

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 顾芸

作者单位： 南通大学

项目金额： 70万元

中文摘要： 细胞外基质在建立和维持适宜组织再生的微环境中起着关键作用。各种去细胞组织已被应用于组织工程领域，但面临材料来源，病原体转移，机械性能不足，和不可控的降解动力学等问题。与之相比，细胞来源的细胞外基质经过细胞的无菌扩增培养，排除了材料不足及病原体转移问题，且与组织工程材料相结合获得可控的降解速度和机械性能，成为组织工程的研究热点。本课题以骨髓间充质细胞分泌的细胞外基质与神经支架材料重组，构建细胞外基质修饰的组织工程神经移植物，并用其桥接大鼠坐骨神经缺损观察修复效果，以开发一种新型组织工程神经。通过基因芯片及MicroRNA芯片分析神经损伤及再生过程中的基因表达变化，以期系统的揭示组织工程神经移植物对神经再生能力的影响及相关机制。质谱分析骨髓间充质细胞，施万细胞及正常坐骨神经组织的细胞外基质，获得影响神经再生的重要基质组分及配比，为体外合成及重构适合神经再生的多聚化胞外基质支架材料提供基础。

中文关键词： 细胞外基质；骨髓间充质细胞；神经组织工程；壳聚糖/丝素蛋白；周围神经损伤

英文摘要： The extracellular matrix (ECM) is a rich meshwork of proteins and proteoglycans, plays a prominent role in establishing and maintaining an ideal microenvironment for tissue regeneration. ECM derived from tissues has been used as biological scaffolds in the fields of tissue engineering. But they may suffer from several drawbacks, including tissue scarcity, pathogen transfer, insufficient mechanical properties, and uncontrollable degradation kinetics. In contrast, cultured cell-derived ECM scaffolds are beginning to attract attention because the former excludes pathogen transfer when cultured and expanded under pathogen-free conditions, and maintains the desired geometry and flexibility when reconstituted with common biomaterials either of synthetic or natural origin. Here we aimed to develop a tissue engineered nerve scaffold by reconstituting bone mesenchymal cell-derived ECM with natural biomaterials, which was used to bridge a 10 mm rat sciatic nerve gap, and observed the regenerative outcomes by morphological analysis as well as electrophysiological examination. In order to systematic reveal the influence and the related mechanism of the ECM-modified tissue engineering nerve graft in nerve regeneration, the gene expression profile chip and microRNA chip technology were used. Moreover, the important components of matrix and their ratio that influence nerve regeneration were obtained by mass spectrometric analysis of extracellular matrix drived from bone mesenchymal cells, Schwann cells or nerve tissue, to provide the basis for the in vitro synthesis and reconstruction the multimerization extracellular matrix scaffold for nerve regeneration.

英文关键词： Extracellular matrix (ECM);Bone mesenchymal cell;Nerve tissue engineering;Chitosan/silk fibroin;Peripheral nerve injury