The long-term objective of this research is the development of a generalized surface treatment to improve the blood compatibility of materials used in various medical devices. The focus is on methods to increase material affinity for albumin, a bystander molecule in most blood-foreign surface interactions. Several such methods have been developed, culminating in an extremely promising one, based on the hydroxylation of a vinyl-methyl-siloxane monomer, which offers high albumin affinity and generality of application. We propose to assess the biocompatibility of very thin, hydrophilic films created from the hydroxylated siloxane. Also evaluated will be a more hydrophobic siloxane film, obtained by C18 acylation at the OH site. These two films represent opposite poles of the strategies we have developed to enhance the albumin affinity of polymers. Simplified membrane oxygenator circuits will be uniformly coated with the test materials, or with underivatized siloxane polymer. The O2 and CO2 permeabilities of these polymers are so high and the film thicknesses so low that the oxygenator gas exchange capacity is unchanged. A canine model of extracorporeal membrane oxygenation (ECMO), the animal perfused in the partial veno-arterial mode, will be used for this evaluation. Regional kinetics of platelet uptake and release will be measured, using quantitative (111)In-oxine labeled platelet imaging in the oxygenator circuit and in the animal. Radiolabeled platelet or fibrinogen accumulation will be measured simultaneously with radiolabeled albumin retention in separate in vivo ECMO experiments. Other studies will evaluate the activation of complement proteins by the treated materials. The biocompatibility studies will be supported by detailed physicochemical characterizations of treated surfaces and in vitro adsorption/desorption profiles of selected plasma proteins. Hypotheses to be tested are: Albumin binds preferentially to OH-and C18 treated siloxane films in vitro; the albumin affinity of treated surfaces is retained in vivo; the surface treatments decrease the rate and amount of platelet uptake on ECMO circuits and in internal organs; inhibition of platelet or fibrinogen accumulation is linked to retention of albumin on treated surfaces; treated surfaces inhibit complement activation.
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