3D微图形化静电纺丝神经定向再生仿生支架复合NSCs修复CST环路损伤界面及在轴突导向中的作用

Directional regeneration under axons guidance is the key to recover neural functions after spinal cord injury (SCI). Nerve tissue engineering scaffolds with different performances may induce directional regeneration of injured axons at different levels. In previous studies, we found that cell interfacial behavior played a significant role in axons guidance, 3D topology of directional nanofibers could impact interfacial behaviors of nerve cells by “contact guidance”, and prompted axons directional migration and directional regeneration. This study will create new 3D micro-graphical electrospun bionic scaffolds of nerve directional regeneration combined with neural stem cell (NSCs) to repair injured interface of corticospinal tract (CST) loops and promote the recovery of neural functions after spinal cord injury. In addition, through the point of “3D micro-graphical electrospun bionic scaffolds of nerve directional regeneration combined with NSCs to repair CST injured interface and the dynamic evolution of axons directional regeneration”, we observe and analyze the relationship between the reconstruction of CST loops and the recovery of motor functions after transplantations , and reveal the effect of 3D micro-graphical electrospun bionic scaffolds of nerve directional regeneration combined with NSCs in axons guidance and regeneration. This study will contribute to promote the development of central nervous system repairment and regeneration, discover the new compensatory mechanism after spinal cord injury, and enhance the value of nerve tissue engineering scaffolds on clinical application.

轴突导向下定向再生是脊髓损伤（SCI）神经功能恢复的关键，不同性能的神经组织工程支架可不同程度地诱导损伤轴突定向再生。本项目前期研究中发现，细胞界面行为对轴突导向具有重要作用，取向排列纳米纤维的3D拓扑结构可通过“接触引导”机制影响神经细胞的界面行为，促使轴突靶向迁移、定向再生。本研究拟创建新型3D微图形化静电纺丝图形化神经定向再生仿生支架复合神经干细胞（NSCs）修复皮质脊髓束（CST）环路损伤界面，促进脊髓损伤后的神经功能恢复。并以“观察3D微图形化静电纺丝神经定向再生仿生支架复合NSCs移植修复CST损伤界面与轴突定向再生动态演进变化”为切入点，观察分析其移植后CST环路重建与运动功能恢复的关系，阐述3D微图形化静电纺丝神经定向再生仿生支架复合NSCs移植在轴突导向与再生中的作用。本研究将有助于推动中枢神经再生修复研究进展,挖掘脊髓损伤代偿新机制,提升神经组织工程支架的临床应用价值。

生物材料搭载种子细胞原位移植治疗脊髓损伤是目前的研究热点。静电纺丝纳米纤维膜已被证实可以作为载体搭载细胞应用于脊髓损伤中。本研究中利用特殊滚轮装置模具制备有序的定向图案化静电纺丝纤维膜，同时按照计划书内容引入蚕丝蛋白（Silk Fibroin, SF）作为纺丝主要成分，成功制备了SF/PLGA图案化纳米纺丝纤维膜，并将其与传统的无序纳米纺丝膜和不含SF的纳米纺丝膜，从材料表征，体内和体外实验等多个角度进行了对比。本课题首先系统研究了新材料的超微结构，接触角等表征测定，随后于体外观察了其对于神经干细胞（Neural Stem Cells, NSCs）增殖和分化的效应，最后构建脊髓全切损伤动物模型，将搭载NSCs的SF/PLGA图案化纳米纺丝膜原位移植入脊髓损伤处，对大鼠的运动功能及相关修复机制进行探讨。我们的结果表明SF在材料中的引入可以有效增加材料的促NSCs增殖作用，而图案化纺丝超微结构则主要侧重增加NSCs向神经元的分化效率，因此相对于本课题中的其他类型纳米纺丝膜，SF/PLGA图案化纺丝不仅可以依靠促进其表面NSCs增殖和分化，同时其还可以作为NSCs的优良载体完成材料和NSCs的双重原位递送，为损伤处建立桥梁，并达到NSCs在该处的富集，促进NSCs向神经元的分化，以及轴突再生和神经环路的重建，从而最终提高大鼠的运动功能。这种图案化纺丝搭载外源性NSCs的原位递送也为脊髓损伤的修复提供一种新的思路。

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