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. The inevitability of thrombus formation on biomaterial surfaces in contact with blood requires the presence of an antithrombotic agent to enable clinical use, with possible complications. Therefore, the development of biomaterials with improved blood compatibility is an important objective. For polymeric biomaterials, options for improving blood compatibility are polymer synthesis, formulation and modification, with modification the focus of this project. Modification approaches studied in this project were the increase in polymer hydrophilicity by utilisation of poly(ethylene oxide), alterations to cellulose by chemical modification and the attachment of the anticoagulant heparin and the preparation of biomembrane-mimetic surfaces. Material assessment covered protein adsorption and an in vitro blood compatibility evaluation. The protein adsorption study investigated the influence of materials on fibrinogen and albumin, as determined by radioactivity measurement of 125I-labelled single protein. The emphasis in the blood compatibility evaluation was on complement activation, as represented by measurement of C3a generation, and the contact phase activation of blood coagulation, as represented by measurement of factor Xll-like activity (FXHA). The blood compatibility evaluation required the establishment of a modified incubation test cell capable of providing a consistent area of material in contact with blood and a response appropriate to the selected parameter measurement. The protein adsorption studies demonstrated that both the type of polymer surface and the modification procedure influence the adsorption. A pronounced 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. The blood compatibility assessment indicates that alterations to polymer surfaces can strongly influence complement activation but have little influence on contact activation. The evidence confirms the potential of polymer modification as a means of improving blood compatibility and supports the further investigation of the relationship between modification and different features of the blood response.

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