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Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides

Authors
 Won Sup Choi  ;  Yoon Ki Joung  ;  Yunki Lee  ;  Jin Woo Bae  ;  Han Ki Park  ;  Young Hwan Park  ;  Jong-Chul Park  ;  Ki Dong Park 
Citation
 ACS APPLIED MATERIALS & INTERFACES, Vol.8(7) : 4336-4346, 2016 
Journal Title
ACS APPLIED MATERIALS & INTERFACES
ISSN
 1944-8244 
Issue Date
2016
MeSH
Animals ; Aorta, Abdominal/drug effects ; Aorta, Abdominal/growth & development ; Blood Vessel Prosthesis* ; Cell Adhesion/drug effects ; Cell Proliferation/drug effects ; Heparin/chemistry ; Heparin/therapeutic use ; Human Umbilical Vein Endothelial Cells ; Humans ; Oligopeptides/chemistry ; Oligopeptides/therapeutic use* ; Polyurethanes/chemistry ; Polyurethanes/therapeutic use ; Rabbits ; Thrombosis/pathology ; Thrombosis/therapy*
Keywords
antithrombogenic activities ; cell-adhesive peptide ; endothelialization ; heparin ; polyurethane ; vascular graft
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.
Full Text
http://pubs.acs.org/doi/abs/10.1021/acsami.5b12052
DOI
10.1021/acsami.5b12052
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Hwan(박영환) ORCID logo https://orcid.org/0000-0001-9802-8017
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
Park, Han Ki(박한기) ORCID logo https://orcid.org/0000-0002-7472-7822
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146597
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