title: Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization.
abstract: Polyurethanes have been investigated for use as vascular grafts due to their excellent mechanical properties and relatively good biocompatibility. However, poor retention of endothelial cells and thrombogenicity in vivo remain problematic for vascular graft applications. The peptide YIGSR has been shown to increase endothelial cell adhesion but not attachment of platelets, suggesting its possible utility for vascular graft applications. In this study, a bioactive polyurethaneurea has been synthesized by incorporating GGGYIGSRGGGK peptide sequences into the polymer backbone. Successful incorporation of the peptides was confirmed by NMR, contact angle measurement and ESCA. Uniform distribution of peptides on the surface was observed using a fluorescent probe capable of reacting with tyrosine residues on the peptides. Hard segment domains were visualized using tapping mode AFM. Endothelial cell adhesion, spreading, proliferation, migration and extra-cellular matrix production were improved on bioactive polyurethaneurea compared to control polyurethaneurea. Competitive inhibition of endothelial cell attachment and spreading by soluble YIGSR peptides indicated that cell adhesion and spreading were specifically mediated by YIGSR-sensitive cell adhesion receptor, not just by changed surface properties. There was no significant difference in the number of adherent platelets. Therefore, this bioactive polyurethanurea may improve vascular graft endothelialization without increasing thrombogenicity.
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main Street MS 142, Houston, TX 77005-1892, USA.
authors.forename: Ho-Wook
authors.initials: HW
authors.lastname: Jun
authors.forename: Jennifer
authors.initials: J
authors.lastname: West
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology; D001667:Binding, Competitive; D001807:Blood Vessel Prosthesis; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D002850:Chromatography, Gel; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000494:pharmacology*; D004548:Elasticity; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission; D017550:Spectroscopy, Fourier Transform Infrared; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods; D017155:Wettability
chemical_list: D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D011140:Polyurethanes; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; C044690:polyetherurethane urea; D009327:4-Chloro-7-nitrobenzofurazan