IMMOBILIZATION OF POLY(ETHYLENE GLYCOL) ONTO A POLY(VINYL ALCOHOL) HYDROGEL .2. EVALUATION OF THROMBOGENICITY

Immobilized polyethylene glycol (PEG) reduced the amount of bovine ser um albumin (BSA) adsorbed on polyvinyl alcohol (PVA) hydrogel, but did not reduce the platelet reactivity of the hydrogel surface. PEG, mole cular weight (MW) 2000 or 5000, with or without a monomethoxy end grou p, was covalently bound to glutaraldehyde-crosslinked PVA either throu gh a cyclic acetal or an urethane functional group with a surface cove rage of 70% (as measured by x-ray photoelectron spectroscopy [XPS]). I mmobilization of monomethoxy-PEG via a cyclic acetal reduced BSA adsor ption to PVA from 11 +/- 2 nmol/m2 to 3.9 +/- 0.3 nmol/m2 and 3.3 +/- 0.3 nmol/m2 for MW 2000 and 5000, respectively. Similarly, urethane bo und PEG reduced adsorption to 3.5 +/- 1.6 nmol/m2 for MW 2000 and 5.4 +/- 1.0 nmol/m2 for MW 5000. Whole blood clotting times of PVA (using a Chandler loop) were not affected by covalently linked PEG, although the initial rate of thrombin generation at the surface, measured using a fluorogenic substrate, was marginally reduced; a rate constant of 4 .2 +/- 0.1 cm/sec and 3.5 +/- 0.1 cm/sec were obtained for MW 2000 and 5000, respectively, compared to 5.6 +/- 1.0 cm/sec for PVA. Ex vivo e valuation using a canine arteriovenous shunt revealed that the hydroge l, with or without bound PEG, reduced circulating platelet levels by 3 5-70% after 4 days. The initial fractional rate of platelet destructio n determined from measurement of platelet cyclooxygenase activity, ind icated that cyclic acetal or urethane bound PEG of either molecular we ight had no effect on platelet consumption produced by PVA. The PEG hy pothesis at least as it relates to platelet interactions may need to b e evaluated further in the light of these results. (C) 1993 John Wiley & Sons, Inc.