生物3D打印载药微米纤维/仿生脱细胞脊髓水凝胶复合支架基于Wnt/β-catenin信号通路修复脊髓损伤的作用机制研究

脊髓损伤（SCI）是一种高致残率的疾病，有限的再生能力及局部胶质瘢痕抑制性微环境是造成SCI再生恢复困难的主要原因，我们前期发现仿生脱细胞脊髓支架复合缓释PTEN抑制剂可以促进大鼠脊髓损伤后神经元与轴突有效再生及功能恢复，但轴突生长锥定向生长重建神经环路依然困难，提示有序仿生微环境引导轴突导向再生，提供“桥梁”是重建神经环路防治SCI的关键科学问题，我们发现调控Wnt/β-catenin信号能够对神经干细胞分化调节，激发神经元定向分化及轴突再生。因此，本项目拟通过构建生物3D打印载药微米纤维/仿生脱细胞脊髓水凝胶复合支架靶向局部调控 Wnt/β-catenin 信号通路治疗SCI，在整体、细胞与分子水平阐明有序仿生支架平台结合局部Wnt/β-catenin信号调控对SCI修复的作用及其调控神经细胞增殖分化的细胞与分子机理，为靶向SCI修复重建提供新的方法与思路。

Spinal cord injury (SCI) is a disease with high disability rate. Limited regeneration ability and local glial scar inhibitory microenvironment are the main cause for the difficulty of SCI regeneration. In the previous study, we found that the controlled slow-release PTEN inhibitor by biomimetic acellular spinal cord can promote the neurons regeneration and functional recovery in rats after spinal cord injury, but it is still difficult to reconstruct the neural loop by the directional growth of axon. It is suggesting that the key scientific problem of reconstructing the neural loop to prevent SCI is to provide a "bridge" and guide the axon to regenerate in an orderly biomimetic microenvironment. We noticed that regulating Wnt/β-Catenin signaling can modulates the differentiation of neural stem cells, promotes the differentiation of neurons and axon regeneration. Therefore, the aim of this project is to construct a biological 3D printing drug loaded micron fiber/biomimetic acellular spinal cord hydrogel composite scaffold targeting local Wnt/β-Catenin signaling pathway in the treatment of SCI. To elucidate the effects of ordered biomimetic scaffolds combined with local Wnt/β-Catenin signaling regulator on SCI repairment and to study the cellular and molecular mechanisms in regulating the proliferation and differentiation of neurons. We aimed to provide a new methods and ideas for SCI repair and regeneration.