Biofunctionalized Electrospun PCL-PIBMD/SF Vascular Grafts with PEG and Cell-Adhesive Peptides for Endothelialization.

Abstract

Artificial small-caliber vascular grafts are still limited in clinical application because of thrombosis, restenosis, and occlusion. Herein, a small-caliber vascular graft (diameter 2mm) is fabricated from poly(ε-caprolactone)-b-poly(isobutyl-morpholine-2,5-dione) (PCL-PIBMD) and silk fibroin (SF) by electrospinning technology and then biofunctionalized with low-fouling poly(ethylene glycol) (PEG) and two cell-adhesive peptide sequences (CREDVW and CAGW) with the purpose of enhancing antithrombogenic activity and endothelialization. The successful grafting of PEG and peptide sequences is confirmed by X-ray photoelectron spectroscopy. The suitable surface wettability of the modified vascular graft is testified by water contact angle analysis. The surface hemocompatibility is verified by platelet adhesion assays and protein adsorption assays, and the results demonstrate that both platelet adhesion and protein adsorption on the biofunctionalized surface are significantly reduced. In vitro studies demonstrate that the biofunctionalized surface with suitable hydrophilicity and cell-adhesive peptides can selectively promote the adhesion, spreading, and proliferation of human umbilical vein endothelial cells. More importantly, compared with control groups, this biofunctionalized small-caliber vascular graft shows high long-term patency and endothelialization after 10 weeks of implantation. The biofunctionalization with PEG and two cell-adhesive peptide sequences is an effective method to improve the endothelialization and long-term performance of synthetic vascular grafts.