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Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides Won Sup Choi,†,¶ Yoon Ki Joung,‡,¶ Yunki Lee,† Jin Woo Bae,† Han Ki Park,§ Young Hwan Park,§ Jong-Chul Park,⊥ and Ki Dong Park*,† †
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea § Department of Thoracic and Cardiovascular Surgery and ⊥Department of Medical Engineering, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ‡
ABSTRACT: The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU−PEG−Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of α-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible. KEYWORDS: vascular graft, polyurethane, heparin, cell-adhesive peptide, antithrombogenic activities, endothelialization
1. INTRODUCTION Cardiovascular and peripheral vascular diseases are well-known major causes of morbidity and mortality with current mortality rates of over 30% worldwide.1,2 However, the increasing needs for vascular prostheses have not yet been satisfied with limited availability of autologous vessels and small-caliber (
