具有电刺激作用的三维梯度β-TCP复合神经导管材料的研究

Nerve conduits play an essential role in the repair of peripheral nerve defects. However, the currently known nerve conduits cannot achieve an ideal reparative effect on morphological and functional reconstruction. Especially, they are not suitable for long peripheral nerve injuries. In this study, a β-tricalcium phosphate/polylactic acid/hyaluronic acid/chitosan/nerve growth factor (β-TCP/PDLLA/HA/CHS/NGF) nerve conduit with electrical stimulation is constructed to induce the regeneration of defect peripheral nerve. By utilizing electrically polarized β-TCP nano-composite, electrostatic self-assembly, cross-coupling technology, thermally-induced phase separation and sugar template leaching, a conduit with a good permeability, multiple channels, multi-level pores, dual gradients in composition and structure, and a well controllable degradation profile will be obtained. This novel scaffold is expected to improve the attachment of cell and growth factor and prevent connective tissue invasion, to promote the speed and quality of directional nerve regeneration and obtain an ideal recovery outcome, and to meet the major demands of clinical peripheral nerve injury repair. To study the property - function relationships between the material and tissues, the surface properties of material, the degradation profiles, the mechanical properties, the cell adhesion and proliferation, and the tissue regeneration will be explored. The microenvironments, the effect of electrical stimulation, and the function of NGF in nerve regeneration will also be studied to understand the mechanism of nerve regeneration induced by the material. The animal experiments will be carried out to explore effective methods to repair peripheral nerves, especially for the long defective peripheral nerves. It is expected to provide new ideas for the design of ideal nerve conduits, open new avenues for the regeneration of long-segment defective nerve, and provide the theoretical basis for clinical studies.

神经导管在周围神经修复中至关重要，但当前研究的神经导管多无法达到理想的形态和功能重建，特别不适于长节段的周围神经损伤修复。项目拟构建一种具有电刺激作用的三维梯度β-TCP/PDLLA/HA/CHS/NGF神经导管。以电极化β-TCP纳米复合、静电自组装和交联偶合技术及热致相分离和糖模板法，获得组成梯度及高通透性、多级孔和多腔道结构梯度的导管，且降解性能可控。以期解决细胞和生长因子趋附及结缔组织入侵等难题，提高神经定向再生的速度和质量并改善修复效果。研究导管降解性能、力学性能和表面特性等与细胞黏附、增殖生长及神经定向再生的关系，揭示材料性能与组织功能之间的联系；研究微环境、电刺激和NGF在神经再生中的作用，探讨材料多方位诱导神经再生的作用机制。进行动物实验，探索周围神经特别是长节段周围神经修复的有效方法。为设计理想的神经导管提供新思路，为长节段损伤神经再生开辟新途径，为临床研究奠定理论基础。

神经导管在周围神经修复中至关重要，但当前研究的神经导管多无法达到理想的形态和功能重建，特别不适于长节段的周围神经损伤修复。项目基于生物相容性、降解性和力学性能等组织工程材料的基本要求，结合神经生长因子的诱导作用和电刺激、中药等的联合作用，联合静电自组装、交联偶合技术及热致相分离和糖模板法等技术，获得组成梯度及高通透性、多级孔和多腔道结构梯度的导管，且降解性能可控。以期解决细胞和生长因子趋附及结缔组织入侵等难题，提高神经定向再生的速度和质量并改善修复效果。研究了导管降解性能、力学性能和表面特性等与细胞黏附、增殖生长及神经定向再生的关系。研究了微环境、电刺激、中药和NGF在神经再生中的作用，探讨材料多方位诱导神经再生的作用机制。利用动物实验，探索周围神经特别是长节段周围神经修复的有效方法。为设计理想的神经导管提供新思路，为长节段损伤神经再生开辟新途径，为临床研究奠定理论基础。研究结果表明具有结构和成分梯度的神经导管具有较好的促神经生长作用；具有良好的载药功能的水凝胶能同时携栽神经生长、中药和电刺激物质，能联合发挥促神经生长作用，具有较好的临床应用价值。. 项目按任务书要求全面完成了研究内容，共发表文章20篇，申请专利13项，其中授权5项，培养硕士研究生9名。超额完成项目要求的各项指标。