All synthetic materials which contact blood experience problems with blood compatibility. The rapid adsorption of plasma proteins and subsequent adherence and activation of platelets leads to thrombus formation. When patients are implanted with vascular devices or undergo hemodialysis procedures, maintenance levels of anticoagulants must be given to prevent life-threatening clot formations. However, these drugs have very dangerous side effects. Preparation of non-thrombogenic device polymers would reduce the need for such high levels of these drugs. For this project we propose to use photochemical coupling reagents to surface-modify biomedical device materials for thrombosis prevention. Hydrophilic materials will be immobilized to prevent plasma protein deposition, and heparin will be attached to the ends of these spacers to give the surface anticoagulant activity. Photochemistry is chosen, since this chemistry allows generic coupling to a wide range of medial device polymers. We will prepare several photoactivatible reagents, then demonstrate photoimmobilization of these reagents to relevant materials. Next, in vitro anticoagulant and platelet adherence and activation assays will be conducted to evaluate the efficacies of the modified surfaces. These in vitro analyses will lead to additional chemistry optimization and ex vivo shunt testing of thrombogenicity and general hemacompatibility during the Phase II portion of this project.
