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 not 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 causes 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 roles 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 a certain amount of rat and rabbit experiments 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 out 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.