Polyurethane Surfaces Bearing Immobilized Thrombin Binding Agents: Preparation and Interactions with Plasma

Abstract

<p>Novel polyurethanes bearing O-phe-pro-arg chloromethylketone (PPACK), sulphonate groups and polyethylene oxide were synthesized using block copolymerization and chain-grafting methods. The structure and the PPACK attachment mode of the PPACK-bearing polyurethane were studied by 2D NMR. The distribution of the functional groups on the corresponding biomaterial surfaces was studied by XPS. PPACK was grafted onto the polyurethane chains in such a way that its bioactivity (interactions with thrombin) was retained. The protein layers deposited from plasma onto the different polymer surfaces were studied by SDS-PAGE in conjunction with immunoblotting methods. The initiation and generation of active coagulation factors in plasma contacting different polymer surfaces were investigated by chromogenic substrate methods using specific oligopeptide substrates. The polyurethane bearing PPACK residues effectively inhibited the activation and generation of factor Xlla and thrombin in plasma contacting the surface, and prevented the clotting of the plasma. This much improved in vitro biocompatibility indicated the validity of using non-heparin antithrombin agents to prevent surface induced coagulation, and it showed that the PPACK-based polymers have potential as novel biomaterials to improve the biocompatibility of current medical devices such as small diameter vascular prostheses, hemodialyzers, stents, and catheters.</p>