Heparinized segmented polyurethaneurea surfaces with hydrophilic spacer groups.

A new heparin-immobilized segmented polyurethaneurea (SPUU, Biomer®) surface using hydrophilic PEO chain as a spacer was developed for surface modification by two different methods. The first method involved the in situ surface immobilization of heparin onto SPUU surface, and the other method utilized the coating of a newly synthesized SPUU-PEO-Heparin graft copolymer. The in situ surface immobilization procedure involved the coupling of telechelic diisocyanate-derivatized PEO spacer to SPUU through allophanate and biuret reactions. The reactions leave a free isocyanate on the spacer group which was then coupled through a condensation reaction to functional groups (-OH, NHb2) on heparin. In situ heparin-immobilized SPUU surfaces were evaluated in vitro, ex vivo, and in vivo to investigate the efficacy of heparin immobilization using long PEO spacers and the effect of spacer length on their biological response with blood. The heparin-immobilized surface demonstrated a much improved blood compatibility when compared to SPUU and PEO grafted SPUU (without heparin). The surface with long spacer groups had increased in vitro heparin activity and minimized platelet adhesion and activation. This correlated well with the improved blood compatibility in ex vivo rabbit shunts and in vivo canine long term implants. Improved blood compatibility was attributed to the prevention of fibrin net formation by immobilized heparin, resulting in a reduction of fibrin induced platelet aggregation and subsequent thrombus formation. However, the PEO grafted surface without heparin failed to prevent thrombus formation in whole blood, although it reduced in vitro platelet adhesion and activation. A new SPUU-PEO-Heparin graft copolymer was synthesized by a similar synthetic procedure as used for in situ surface immobilization and characterized to investigate the interaction between the blood and copolymer surface. Biological responses with blood in in vitro and ex vivo were comparable to an in situ surface immobilized system and attest to the usefulness of this new procedure as a coating to improve the blood compatibility of blood contacting surface.