Modification of polymeric biomaterials for improved blood compatibility : investigation of protein adsorption and in vitro blood response

Polymeric biomaterials are widely used in blood contacting devices. Theinevitability of thrombus formation on biomaterial surfaces in contact with bloodrequires the presence of an antithrombotic agent to enable clinical use, with possiblecomplications. Therefore, the development of biomaterials with improved bloodcompatibility is an important objective. For polymeric biomaterials, options forimproving blood compatibility are polymer synthesis, formulation and modification,with modification the focus of this project. Modification approaches studied in thisproject were the increase in polymer hydrophilicity by utilisation of poly(ethyleneoxide), alterations to cellulose by chemical modification and the attachment of theanticoagulant heparin and the preparation of biomembrane-mimetic surfaces.Material assessment covered protein adsorption and an in vitro blood compatibilityevaluation. The protein adsorption study investigated the influence of materials onfibrinogen and albumin, as determined by radioactivity measurement of 125I-labelledsingle protein. The emphasis in the blood compatibility evaluation was oncomplement activation, as represented by measurement of C3a generation, and thecontact phase activation of blood coagulation, as represented by measurement offactor Xll-like activity (FXHA). The blood compatibility evaluation required theestablishment of a modified incubation test cell capable of providing a consistent areaof material in contact with blood and a response appropriate to the selected parametermeasurement. The protein adsorption studies demonstrated that both the type ofpolymer surface and the modification procedure influence the adsorption. Apronounced reduction in protein adsorption was obtained with a biomembrane-mimetic surface. Increase in hydrophilicity by the utilisation of poly(ethylene oxide)can increase albumin adsorption and markedly reduce fibrinogen adsorption. Theblood compatibility assessment indicates that alterations to polymer surfaces canstrongly influence complement activation but have little influence on contactactivation. The evidence confirms the potential of polymer modification as a meansof improving blood compatibility and supports the further investigation of therelationship between modification and different features of the blood response.

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