Thromboresistant surfaces, immobilized heparin

Other concerns regarding the practicality of surface bound heparin for the preparation of materials with long-term thromboresistance remain. Because the interaction of heparin with platelets is unclear (31), whether the immobilized heparin causes greater thrombosis under conditions where platelet deposition is more important than fibrin formation remains to be shown. The passivating effect of antithrombin III on platelet consumption caused by surface-bound heparin is a significant observation in this context (32, 33). 

The results reported here, in conjunction with earlier results, indicate that immobilized heparin need not necessarily be lost from a surface in order to impart thromboresistance to that surface. For heparin-PVA, and perhaps for other covalent reactions that do not inactivate the heparin, the irreversibly bound heparin can accelerate the formation of a surface-bound inactive thrombin-antithrombin III complex. Furthermore, our results suggest that the inactive complex is not itself permanently bound to the surface, but rather can be displaced by a component or components in plasma. 

To circumvent many of these undesired side effects associated with systemic heparin administration, many investigators have endeavored to immobilize heparin to blood-contacting polymers to form thromboresistant surfaces. Considering that heparin binds to the endothelium following systemic injection (I), this approach appears attractive. 

A semi-interpenetrated network was obtained by bulk polymerization of 2-hydroxye-thyl methacrylate incorporated in DMF treated PET films by solvent-exchange technique, followed by treatment of films in e-lectrical discharges. Heparinization was accomplished by reacting glutaraldehyde with heparin and poly(2-hydroxyethyl methacrylate) present on the surface of modified polyester films. The immobilization of heparin was indirectly evidenced by chromatographying the silylated hydrolyza-tes of heparinized PET films and heparin, respectively. In vitro experiments demonstrated the enhanced thromboresistance of heparinized films. 

The strategy we adopted in developing thromboresistant, heparin-immobilized surfaces is ... 

---