小口径人工血管的再狭窄发生率高，制约了其临床应用。研究的瓶颈主要是对血管再生的机制还没有认识清楚，需要解决的是快速内皮化、中膜外膜再生以及远期再狭窄问题。在老年和疾病条件下血管再生困难，后期发生内皮功能退化、血管壁钙化和新内膜增生，导致血管再狭窄或堵塞。本项目将利用转基因和骨髓移植小鼠进行血管再生机制研究，研究血管再生细胞的来源和迁移途径，认识巨噬细胞的调控机制，发现起关键作用的血管活性物质。制备孔结构和纤维取向适合血管三层膜再生的血管材料，用VEGF、NO、蛋白XBP1和DDK3多肽等活性物质修饰人工血管，优化这些活性物质的配伍、剂量、固定方式、空间分布和释放。进行大量的大鼠和兔体内植入实验，验证小鼠实验发现的血管再生机制，系统研究所构建的活性人工血管的再生性能。进行大动物和疾病模型动物的体内实验，进一步研究人工血管的构效关系和优化人工血管的制备，力争获得具有临床应用前景的人工血管材料。

The high restenosis rate of small-diameter vascular grafts has restrained its clinical application. The main bottle-neck in this research is that the regeneration mechanism of small-diameter vascular grafts is clear yet. The challenge is to achieve rapid endothelialization, regeneration of tunicae media and adventitia and prevention of late stage restenosis. Under the old and sick conditions, the regeneration of vascular grafts is more difficult. The function of endothelium often declines in late stage, which caused vascular wall calcification, neointimal formation and complete occlusion of the implants. In this project, we will use transgenic mice and bone marrow transplantation mice to investigate the regeneration mechanism of vascular grafts, the source of vascular cells and their migration route. We will also investigate the regulatory role of macrophages and explore the key active substances that play critical role in vascular regeneration. Following the mechanism study, we will fabricate vascular grafts with aligned pores and fibers that can well facilitate the regeneration of the three vessel layers. We will further modify these grafts with VEGF, NO, protein XBP1 and DDK3 peptide in suitable composition, dosage, immobilization manner, spatial distribution and release profile. We will perform certain amount of rat and rabbit experiment to verify the regeneration mechanism found in the mouse study and systemically evaluate the regeneration capacity of the small diameter vascular grafts which we prepared with the optimized techniques. In the end, we will carry on large animal tests and evaluation in diseased rats and rabbits to further investigate the effect of structure and bioactive modification on vascular regeneration. These animal experiments will help to further optimize the preparation of vascular grafts which may lead to potential vascular graft products for clinical treatment.