Radiation Physics Chemistry Vol. 22 No. 1/2, pp. 267~283,1983 0146-5724/83/07267-17503.00/0 Printed in Great Britain © 1983Pergamon PressLtd. APPLICATION OF RADIATION-GRAFTED IIYDROGELS AS BLOOD-CONTACTING BIOMATERIALS Allan S. Hoffman, Daniel Cohn, Stephen R. Hanson*, Laurence A. Harker*, Thomas A. IIorbett, Buddy D. Ratner and Larry O. Reynolds Center for Bioengineering, Departments of Chemical Engineering and Nuclear Engineering, and Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA ABSTRACT This article reviews the interactions of radiation-grafted hydrogels with blood and its com- ponents, both in vitro and in vivo. It has been found that as the hydrogel water content increases for radiation-grafted hydrogels of moderate to high water contents (15-85%) they tend a) to adsorb fewer protein molecules, and to desorb them more readily in vitro, b) to form thrombus but to adhere the thrombi less readily in the in vivo canine ring tests, and c) to cause more rapid formation and greater volumes of platelet microemboli in the ex vivo A-V femoral baboon shunt. At low water contents (below 10%) the grafted HEMA/EMA copolymer "hydrogels" exhibit an unexpected minimum in platelet consumption, which may be related less to the absorbed water in the graft copolymer than to the polymer composition at the surface. These results suggest that special radiation graft copolymer compositions may be selected to fit specific biological needs. Keywords. Biomaterials, radiation graft copolymers, hydrogels, blood-biomaterial inter- actions, polymer surface characterization, platelet consumption, baboon femoral shunt. INTRODUCTION A hydrogel can be defined as a polymeric material which exhibits the ability to swell in water and retain a significant fraction (e.g., > 10%) of water within its structure, but which will not dissolve in water. Hydrogels with relatively high water contents have a soft, rubbery consistency when wet, which can give them a strong, superficial resemblance to living, soft tissues. These properties help to make hydrogels a useful class of biomaterial. For example, high swelling of the hydrogel structure can confer high permeability to small molecules, which should allow polymerization initiator molecules, initiator decomposition products, polymerization solvent molecules, and other extraneous materials to be efficiently extracted from the gel network before the hydrogel is placed in contact with a living system. The in vivo leaching of additives used during the fabrication of polymeric materials can cause inflammation and eventual rejection of implanted biomaterials. Furthermore, the ability of small molecules to diffuse through hydrogels may be advantageous for hydrogel performance in vivo. The diffusion of important low molecular weight metabolites and ions through the implant and to the adjacent tissues could occur within hydrogels, but not within relatively hard, impermeable plastics. Concerning their mechanical properties, the rather soft and rubbery consistency of water-swollen hydrogels can contribute to their usefulness as biomaterials by minimizing mechanical (frictional) irritation to surrounding cells and tissues. Another property of hydrogels which may contribute to their usefulness as biomaterials is the low interfacial tension between a hydrogel surface and an aqueous solution. This low interfacial tension should reduce the tendency of the proteins in body fluids to adsorb strongly and unfold upon adsorption (Hoffman, 1974). Minimal protein interaction may be important for the biological acceptance of foreign biomaterials, since the denaturation of proteins by foreisn surfaces could serve as a trigger mechanism for the initiation of * Present address: Scripps Research Foundation, La Jolla, California. Please address all reprint requests to Prof. Allan S. Hoffman. 267