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, Jongchul Park, Ki Dong Park

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4336-4346
Number of pages11
JournalACS Applied Materials and Interfaces
Volume8
Issue number7
DOIs
Publication statusPublished - 2016 Feb 24

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Grafts
Peptides
Heparin
Adhesives
Polyurethanes
Endothelial cells
tyrosyl-isoleucyl-glycyl-seryl-arginine
glycyl-arginyl-glycyl-aspartyl-serine
Elastomers
Electrospinning
Platelets
Infiltration
Fibrinogen
Polyethylene glycols
Adhesion

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

Cite this

Choi, Won Sup ; Joung, Yoon Ki ; Lee, Yunki ; Bae, Jin Woo ; Park, Han Ki ; Park, Young Hwan ; Park, Jongchul ; Park, Ki Dong. / Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides. In: ACS Applied Materials and Interfaces. 2016 ; Vol. 8, No. 7. pp. 4336-4346.
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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.",
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Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides. / Choi, Won Sup; Joung, Yoon Ki; Lee, Yunki; Bae, Jin Woo; Park, Han Ki; Park, Young Hwan; Park, Jongchul; Park, Ki Dong.

In: ACS Applied Materials and Interfaces, Vol. 8, No. 7, 24.02.2016, p. 4336-4346.

Research output: Contribution to journalArticle

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AU - Choi, Won Sup

AU - Joung, Yoon Ki

AU - Lee, Yunki

AU - Bae, Jin Woo

AU - Park, Han Ki

AU - Park, Young Hwan

AU - Park, Jongchul

AU - Park, Ki Dong

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AB - 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.

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