HEPARIN-CONTAINING BLOCK-COPOLYMERS .2. IN-VITRO AND EX-VIVO BLOOD COMPATIBILITY

Newly synthesized heparin-containing block copolymers, consisting of a hydrophobic block of polystyrene (PS), a hydrophilic spacer-block of poly(ethylene oxide) (PEO) and covalently bonded heparin (Hep) as bioa ctive block, were coated either onto glass, poly(dimethylsiloxane), po lyurethane or PS substrates. Coated surfaces were characterized by det ermination of the surface-bound heparin activity, adsorption of AT III , plasma recalcification time assays, adhesion of platelets and by an ex vivo rabbit A-A shunt model. It was demonstrated that heparin was a vailable at the surface of all heparin-bound surfaces to interact with AT III and thrombin and to prevent the formation of clots. The maximu m immobilized heparin activity was found to be 5.5 x 10(-3)U cm-2. Coa ted surfaces showed a significant prolongation of the plasma reclacifi cation times as compared to control surfaces, due to surface-immobiliz ed heparin. The platelet adhesion demonstrated that platelets reacted only minimally with the heparin-containing block copolymers in the tes t system and that the heparin-containing block copolymers seemed to pa ssify the surface as compared to control surfaces. In the ex vivo A-A shunt experiments, which were carried out under low flow and low shear conditions, the heparin-containing block copolymers exhibited prolong ed occlusion times, indicating the ability of the heparin-containing b lock copolymers to reduce thrombus formation at the surface,