Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide promotes endothelialization with decreased platelet adhesion.
Thrombosis and intimal hyperplasia are the principal causes of small-diameter vascular graft failure. To improve the long-term patency of polyurethane vascular grafts, we have incorporated both poly(ethylene glycol) and a diazeniumdiolate nitric oxide (NO) donor into the backbone of polyurethane to improve thromboresistance. Additionally, we have incorporated the laminin-derived cell adhesive peptide sequence YIGSR to encourage endothelial cell adhesion and migration, while NO release encourages endothelial cell proliferation. NO production by polyurethane films under physiological conditions demonstrated biphasic release, in which an initial burst of 70% of the incorporated NO was released within 2 days, followed by sustained release over 2 months. Endothelial cell proliferation in the presence of the NO-releasing material was increased as compared to control polyurethane, and platelet adhesion to polyethylene glycol-containing polyurethane was decreased significantly with the addition of the NO donor.
Taite
Lakeshia J
LJ
Department of Bioengineering, Rice University, Houston, Texas, USA.
Yang
Peter
P
Jun
Ho-Wook
HW
West
Jennifer L
JL
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis; D001807:Blood Vessel Prosthesis; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D011140:Polyurethanes / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001672:Biocompatible Materials; D020030:Nitric Oxide Donors; D009842:Oligopeptides; D011140:Polyurethanes; C030554:co(polyether)polyurethane; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D009569:Nitric Oxide; D011092:Polyethylene Glycols