Heparin releasing and immobilized polymers have demonstrated a significant reduction in thrombus formation on the blood/polymer interface. In vitro studies revealed that prevention of fibrin formation using the designed systems were mainly due to heparin activity, in terms of APTT, TT, and anti- Factor Xa tests. In vivo studies of heparin immobilized surfaces displayed minimum fibrin formation, although platelet adhesion was not significantly reduced. In this application, both commercial and fractionated heparin will be immobilized onto a model surface (Sepharose 6B) and a practical surface (polyurethane) using both hydrophilic and polar spacer arm groups. Based on our previous studies it is expected that the hydrophilic environment of the block spacer interface will reduce protein adsorption and subsequent platelet adhesion. Heparin-PGE1 conjugate will also be immobilized on the surface by similar chemistry to achieve the dual pharmacological actions of reducing fibrin formation and inhibiting platelet adhesion. The experimental parameters, hydrophilic environment via hydrophilic spacer groups, heparin activity, and a heparin-PGE1 conjugate, will be investigated by utilizing a design variable of differing spacer group lengths between the surface and immobilized heparin or heparin-PGE1 conjugate. The animal experiments include rabbit ex vivo shunt (short term) catheter implant (short term) and vascular implant in dogs (long term). The results of the experimental data will verify possible mechanisms involved in thrombus formation (role of adsorbed protein, clotting factors, and platelet interaction) and provide a more effective model for the design of a blood compatible polymer surface. This will eliminate the need or systemic administration of anticoagulants in patients using blood contacting medical devices.
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