具有微/纳米复合纤维结构的小口径人工血管构建及对组织再生的引导作用

The regeneration of vascular smooth muscle is a key problem in the research of small-diameter vascular grafts. It has been reported that a stem/progenitor cell niche exists in the adventitia of the blood vessel, and the resident stem/progenitor cells are important cell source for the repair of artery injury. In order to realize or promote the tissue regeneration after the implantation, a kind of novel vascular grafts with hybrid micro-/nano-fiber structure and bio-mimetic functional surface will be designed and fabricated. The as-prepared vascular grafts could recruit resident stem/progenitor cells and induce in vivo tissue regeneration. By controlling the degradation behavior the ingrowth of cells into the grafts can be improved. By controlling the micro/nano architecture, the inflammatory response of the host can be specifically altered to further stimulate the secretion of the cytokines for neoartery formation. By constructing functional surface, the cell adhesion, migration, and differentiation can be improved. Finally, the in vitro and in vivo evaluations will be performed to investigate the effects of these strategies and the cooperative mechanism of them on the tissue regeneration in order to provide reasonable suggestion for promoting the tissue regeneration.

组织再生特别是平滑肌组织再生一直是小口径人工血管研究中的难点问题之一。很多研究表明在血管外膜中存在一个"细胞龛"，其中存在的干/祖细胞是血管损伤后自发修复的重要细胞来源。本研究以解决人工血管移植后组织再生为主要目的，设计并构建一种具有微/纳米复合纤维结构和仿生功能表面的新型人工血管，使其在体内能够募集自体血管干/祖细胞、引导组织原位再生。通过调控降解行为改善细胞向材料内部的长入；通过控制（微/纳米）空间结构调节宿主的炎症反应、促进血管新生细胞因子的产生；通过构建功能化表面，促进细胞的粘附、迁移和分化。通过体内（外）实验综合评价这些策略的效果和协同作用机制，为解决血管移植后组织再生提供合理的选择。

人工血管移植是治疗心血管疾病的有效手段之一，对于直径小于6mm的小口径人工血管目前还没有产品成功应用于临床。本项目的研究思路是综合考虑植入后不同时期材料在血栓/凝血、炎症反应以及细胞迁移和分化等方面的不同特点，科学地进行结构设计和表面功能化修饰，构建具有诱导组织再生功能的材料微环境。通过利用不同血管活性物质（活性多肽7aa，DKK3，一氧化氮等），采用不同的表面修饰技术（化学接枝、物理吸附、超分子组装等），精确控制其表面组成和分布，针对性调控其释放行为。从而有效提高了血管通畅性，改善了血管组织再生和重构，有利于血管长期稳态的实现。