多级有序石墨烯凝胶构建神经支架及对干细胞定向分化与神经再生的导向作用研究

The repair of peripheral nerve injury is one of major issues in the field of nerve regeneration. Graphene (GE) material with three-dimensional structure is regarded as one of preferred materials for tissue engineering and repair due to its high specific surface area, excellent conductive behavior and biocompatibility, lightweight and self-supporting performances. However, the disordered macroporous structure is disadvantageous for assembly and controlled release of growth factor and directional growth of axons, which hinders the application of three-dimensional GE material as nerve scaffold. In this project, the self-supported GE hydrogel was prepared by a hydrothermal synthesis combined with microfabrication technology. The aperture of GE hydrogel was adjusted by the incorporation of SiO2 nanoparticles and a longitudinal arrangement structure was obtained after microfabrication. After that, the biological molecules of short peptide were modified onto the surface of GE and growth factor was absorbed and assembled into the micro-nano porous structures. The synergistic actions from multihierarchically ordered structure, controlled release of growth factor and electrical stimulation added on the GE scaffold affected the behaviors of cell, such as adhesion and directional differentiation of neural stem cell, neuronal regeneration and directional growth of axons, and the action betweens cells. This project is one cross-subject study of material science, life science, physics and chemistry, and involves design and fabrication of novel material for nerve scaffold, explores the essence and rule of cell behavior regulated by material, and sheds new light on the design, fabrication and potential application of novel material as nerve scaffold in the nerve injury repair.

研究周围神经损伤的修复以及功能重建是神经再生领域的重大课题。三维多孔石墨烯材料以其大比表面积、优异的导电性和生物相容性、超轻、自支撑等优良特性，成为组织工程修复领域的优选材料之一。但其无序大孔结构不利于生长因子装配、控释及轴突的定向生长，限制了作为神经支架材料的使用。本项目结合水热合成及微加工技术构筑自支撑的石墨烯凝胶，借助SiO2纳米粒子实现微纳孔径的调控，获得具有纵向排列特征的多级有序结构；利用表面化学技术将短肽生物分子修饰到三维石墨烯表面，再将生长因子吸附储存在石墨烯微纳多孔结构中；探究多级有序结构、生长因子缓释及电场刺激协同作用对神经干细胞吸附、定向分化、神经元再生、轴突定向生长、细胞间相互作用的影响。本项目是材料科学、生命科学、物理、化学多学科交叉课题，探究材料调控细胞行为的本质和规律，为新型神经支架材料的设计、制备及在神经损伤修复中的应用提供了新的思路。

研究周围神经损伤的修复以及功能重建是神经再生领域的重大课题。三维多孔石墨烯材料以其大比表面积、优异的导电性和生物相容性、超轻、自支撑等优良特性，成为组织工程修复领域的优选材料之一。但其无序大孔结构不利于轴突的定向生长，限制了作为神经支架材料的使用。本项目结合水热合成、微加工技术、取向冷冻技术构筑了石墨烯基水凝胶材料，借助金属氧化物、掺杂手段功能化石墨烯，有效调控了三维石墨烯基复合材料的导电行为和催化活性。通过优化材料成分、微观结构，获得了孔径尺寸、微观形态、导电性、催化活性可控的具有纵向排列特征的多级有序结构材料；掌握了有序结构、材料成分及电场刺激协同作用对神经细胞吸附、定向分化、轴突定向生长、细胞间相互作用的影响规律，并深刻理解了结构影响材料性能及细胞-材料相互作用的本质和规律，为新型石墨烯基复合材料和神经支架材料的设计、制备及在神经损伤修复中的应用提供了新的思路。