自成型仿生神经导管调控脂肪干细胞和血管化促进周围神经原位再生

周围神经缺损的快速有效修复是尚未解决的世界性临床难题之一。基于组织工程构建的神经导管可用于神经再生，但仍然难以修复长段神经缺损。主要原因在于导管内部缺乏有效促进神经再生的仿生信号以及无法形成稳定的为神经再生提供必要营养物质的血管网络。因此，构建既能促血管化又具有神经再生诱导信号的仿生神经导管有望为长段神经缺损的修复带来新的突破。研究发现，导管结构会影响导管移植后的血管化，也是影响神经修复效果的重要因素之一。我们前期构建了自成型多通道神经导管，有效促进了新生血管长入和神经组织再生。本课题将在前期研究基础上结合生物3D打印构建仿生多通道神经导管，同时实现神经营养素NT-3和脂肪干细胞的负载。利用导管结构促进早期血管化，并联合NT-3调控脂肪干细胞的分化及功能，促进周围神经原位再生增强长段神经缺损的修复效果。本研究将为神经导管的构建提供新思路，为长段神经缺损的修复提供新的治疗手段，具有重要意义。

The rapid and effective repair of peripheral nerve defect is one of the unsolved clinical problems in the world. Tissue engineered nerve conduit can be used for nerve regeneration, but it is still difficult to repair large-scale nerve defects. The main reason lies in the lack of biomimetic signals that can effectively promote nerve regeneration and the inability to form a stable vascular network that provides essential nutrients for nerve regeneration. Therefore, the construction of bionic nerve conduit which can promote vascularization and have the signal of inducing nerve regeneration is expected to bring a new breakthrough for the repair of long nerve defect. Studies have found that the structure of the conduit will affect the vascularization after the transplantation, and it is also one of the important factors affecting the effect of nerve repair. In the early stage, we have constructed a self-formed multi-channel nerve conduit, which can effectively promote the growth of new blood vessels and nerve tissue regeneration. On the basis of our previous study, this project will construct a bio-inspired multi-channel nerve conduit combined with biological 3D printing, and realize the loading of NT-3 and adipose derived stem cells at the same time. The multi-channel structure can promote the early vascularization. Using the structure of the conduit and released NT-3 to regulate the differentiation and function of adipose derived stem cells, further promote the in-situ regeneration of peripheral nerve and enhance the repair effect of long nerve defect. This study will provide a new idea for the construction of nerve conduit and a new treatment for the repair of long segment nerve defect, which is of great significance.