Construction of a bilayered vascular graft with smooth internal surface for improved hemocompatibility and endothelial cell monolayer formation

Abstract

Formation of a continuous endothelial cell (EC) monolayer inside the luminal surface with enhanced hemocompatibility, is a promising solution for improving performance and overall patency of small-diameter vascular grafts. There has been much debate regarding the ideal substrate surface topography to achieve this. Here, we investigated different polycaprolactone (PCL)-derived substrate surfaces fabricated from nanofibers, microfibers, or with smooth surfaces, and evaluated their effect on hemocompatibility and EC behavior. Our results demonstrated that, compared with the other two substrates, smooth surfaces inhibited platelet adhesion and activation, suppressed fibrinogen adsorption, and enhanced EC monolayer formation. In addition, smooth surfaces increased EC nitric oxide (NO) production and acetylated low-density lipoprotein (Ac-LDL) uptake. Thus, we designed and fabricated a bi-layered vascular graft composed of a smooth ultrathin internal layer and a microfibrous external layer, which were capable of preventing spiral-flow and decreasing wall-shear stress. Arterio-venous shunt models revealed that bi-layered grafts avoided bleeding and inhibited both protein absorption and platelet adhesion. Overall, these findings indicated that the prepared bi-layered grafts could perform better for in vivo implantation. Furthermore, this approach doesn't require chemical or biological modifications, and therefore can be easily applied to the fabrication of other implantable tubular grafts using various materials.