Acellular Vascular Scaffolds Preloaded With Heparin and Hepatocyte Growth Factor for Small-Diameter Vascular Grafts Might Inhibit Intimal Hyperplasia

Abstract

To develop small-diameter (<6 mm) scaffolds capable of accelerating rapid endothelialization and improving long-term patency rate, we created acellular vascular scaffolds preloaded with heparin and hepatocyte growth factor (HGF). Heparin was conjugated to suppress thrombogenic responses, and HGF was immobilized to induce endothelial cells (ECs) proliferation and migration. The scaffolds immobilized with heparin exhibited highly effective localization and sustained release of HGF for 30 days in vitro. We implanted this modified scaffold into the carotid artery of a rabbit model to investigate the efficacy in vivo. The acellular vascular scaffold with heparin only was used as control. After transplantation, the patency of this modified scaffold was 91.67% at 1, 3, 6, and 12 months, while the patency rate in the group with grafted heparin only was 83.33% at 1, 3, 6, and 12 months. This modified scaffold significantly stimulated ECs proliferation and the endothelium aligned in the direction of flow after 12 months. In addition, intimal hyperplasia was significantly reduced in the grafts coated with HGF compared with the control grafts. The small-diameter vascular grafts with an inner diameter of 2.5 mm preloaded with heparin and HGF may be a substitute for autologous blood vessels in clinic.