Quercetin improves rapid endothelialization and inflammatory microenvironment in electrospun vascular grafts

There is a great need for small diameter vascular grafts among patients with cardiovascular diseases annually. However, continuous foreign body reactions and fibrosis capsules brought by biomaterials are both prone to poor vascular tissue regeneration. To address this problem, we fabricated a polycaprolactone (PCL) vascular graft incorporated with quercetin (PCL/QCT graft) in this study. In vitro cell assay showed that quercetin reduced the expressions of pro-inflammatory genes of macrophages while increased the expressions of anti-inflammatory genes. Furthermore, in vivo implantation was performed in a rat abdominal aorta replacement model. Upon implantation, the grafts exhibited sustained quercetin release and effectively enhanced the regeneration of vascular tissue. The results revealed that quercetin improved endothelial layer formation along the lumen of the vascular grafts at four weeks. Furthermore, the thickness of vascular smooth muscle layers significantly increased in PCL/QCT group compared with PCL group. More importantly, the presence of quercetin stimulated the infiltration of a large amount of M2 phenotype macrophages into the grafts. Collectively, the above data reinforced our hypothesis that the incorporation of quercetin may be in favor of modulating the inflammatory microenvironment and improving vascular tissue regeneration and remodeling in vascular grafts.