Effect of sustained heparin release from PCL/chitosan hybrid small-diameter vascular grafts on anti-thrombogenic property and endothelialization

Abstract

Thrombus formation and subsequent occlusion are the main reasons for the failure of small-diameter vascular grafts. In this study, a hybrid small-diameter vascular graft was developed from synthetic polymer poly(ε-caprolactone) (PCL) and natural polymer chitosan (CS) by the co-electrospinning technique. Heparin was immobilized on the grafts through ionic bonding between heparin and CS fibers. The immobilization was relatively stable, and heparin could continuously release from the grafts for more than 1month. Heparin functionalization evidently improved the hemocompatibility of the PCL/CS vascular grafts, which was illustrated by the reduced platelet adhesion and prolonged coagulation time (activated partial thromboplastin time, prothrombin time and thromboplastin time) as shown in the human plasma assay, and was further confirmed by the ex vivo arteriovenous shunt experiment. In vitro cell proliferation assay showed that heparin can promote the growth of human umbilical vein endothelial cells, while moderately inhibiting the proliferation of vascular smooth muscle cells, a main factor for neointimal hyperplasia. Implantation in rat abdominal aorta was performed for 1month. Results indicate that sustained release of heparin provided optimal anti-thrombogenic effect by reducing thrombus formation and maintaining the patency. Furthermore, heparin functionalization also enhanced in situ endothelialization, thereby preventing the occurrence of restenosis. In conclusion, it provides a facile and useful technique for the development of heparinized medical devices, including vascular grafts.

Keywords: Anti-thrombogenic property; Endothelialization; Heparin; Vascular grafts.