3D打印水凝胶支架结合c-SRC沉默的神经干细胞构建仿生脊髓修复大鼠脊髓损伤的作用及机制研究

神经干细胞（NSCs）移植是治疗脊髓损伤（SCI）的热点，但尚需解决有限的神经元分化率与神经传导回路重建困难的两大难题。我们前期研究证实c-SRC沉默的NSCs移植可通过mTORC1-SREBP1促进NSCs向神经元定向分化及神经再生，并进一步设计了一种3D打印材料组合温敏凝胶结构，结合c-SRC沉默的NSCs构建的仿生脊髓，可实现种子细胞与生物材料可控性有序重组，综上提出科学假设：3D打印仿生脊髓可利用水凝胶结构抑制炎症减少瘢痕有效递送，c-SRC沉默的NSCs分化形成新生神经元和轴突，立体有序微孔管道结构引导再生轴突有序延伸，进而产生更多有效神经纤维参与重建神经回路，更好促进SCI后功能恢复。为验证该假说，本项目拟采用一系列体内外实验，探讨3D打印水凝胶支架结合c-SRC沉默的NSCs构建仿生脊髓通过促进神经元定向分化与神经传导回路重建的作用及机制，明确该仿生脊髓促进SCI修复的优势。

Neural stem cell (NSCs) transplantation is a hot spot in the treatment of spinal cord injury (SCI), but two major problems still need to be solved: the limited neuron differentiation rate and the difficulty in rebuilding nerve conduction circuits. Our previous studies confirmed that the transplantation of c-SRC silenced NSCs can promote the directional differentiation of NSCs into neurons and nerve regeneration through mTORC1-SREBP1, and we further designed a 3D printing material combination temperature-sensitive gel structure, combined with c-SRC silenced NSCs. The bionic spinal cord can realize the controlled and orderly reorganization of seed cells and biological materials. In summary, the scientific hypothesis is put forward: 3D printed bionic spinal cord can use hydrogel structure to inhibit inflammation, reduce scar and delivery effectively, and c-SRC silenced NSCs differentiate to form new neurons and axons, the three-dimensional ordered microporous duct structure guides the regenerated axons to extend in an orderly manner, thereby generating more effective nerve fibers to participate in the reconstruction of neural circuits, and promote functional recovery after SCI. In order to verify this hypothesis, this project plans to use a series of in vivo and in vitro experiments to explore the role and mechanism of 3D printed hydrogel scaffolds combined with c-SRC silenced NSCs to construct a bionic spinal cord by promoting the directional differentiation of neurons and the reconstruction of nerve conduction circuits and to proof the advantages of biomimetic spinal cord in promoting SCI repair.