Polyurethane Copolymers Containing Covalently Attached RGD-Peptide: Synthesis and Cell Adhesion Studies
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POLYURETHANE COPOLYMERS CONTAINING COVALENTLY ATTACHED RGD-PEPTIDE: SYNTHESIS AND CELL ADHESION STUDIES HORNG-BAN LIN AND STUART L. COOPER University of Wisconsin-Madison, Dept. of Chemical Engineering, 1415 Johnson Drive, Madison, Wisconsin 53706
ABSTRACT Synthesis of novel polyurethane copolymers containing covalently attached, well-oriented Arg-Gly-Asp (RGD) peptides was explored. A poly(tetramethylene oxide) based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone. Cell-adhesive peptides GlyArg-Gly-Asp-Ser-Tyr (GRGDSY) and Gly-Arg-Gly-Asp-Val-Tyr (GRGDVY) were covalently bound to the polyurethane backbone via the formation of amide bonds. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. Electron spectroscopy for Chemical Analysis (ESCA) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSYand GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in culture medium. The GRGDVYgrafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide grafted polyurethane copolymers may be useful in providing an easily prepared celladhesive substrate for various biomaterial applications. INTRODUCTION Polyurethane copolymers have been used in a number of blood-contacting applications due to their excellent physical and mechanical properties and relatively good blood compatibility [1). However, the uses of these devices in routine clinical applications has been limited in part by problems associated with surface-induced thrombosis [2]. Invitro endothelialization of artificial surfaces has been suggested as a route to provide a non-thrombogenic vascular prothesis [3, 4]. However, studies [5] showed that the growth of endothelial cells on Biomero (a commercially available polyurethane) is relatively poor unless the surface was precoated with an adhesive substrate to increase cell attachment. In recent years, rapid progress has been made in understanding the molecular interactions that result in cell attachment. A common mechanism that mediates cell adhesion involves broadly distributed cell membrane-associated
Mat. Res. Soc. Symp. Proc. Vol. 252. (c,1992 Materials Research Society
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hetrodimer adhesion receptors called integrins [6, 7]. Many adhesive proteins present in extracellular matrices (ECM) and in the blood stream contain the Arg-Gly-Asp (RGD) sequence in the site recognized by integrins. These pro
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