Thromboresitant Prosthetic Arterial Graft

We will develop a thromboresistant, small diameter prosthetic arterial graft for use in the clinicathere are no acceptable prostheses which can be utilized for vascular repair or replacement in situaconduit with an internal diameter of less that 4mm due to prompt thrombosis. The research objectivein Phase I are 1) chemical modification of a urethane-based polymer; 2) immobilization of the potentanticoagulant hirudin to the modified biomaterial; 3) determination of surface reactivity. The polyube modified such that carboxyl or amine groups will be present on the surface without varying the bipolymer. Recombinant hirudin will then be immobilized on the graft surface. The amount of recombinanthe surface will be evaluated and there will be studies on binding optimization. The immobilized rebe assayed for surface biologic activity using static and flow conditions. Static assay will focus oinhibition, thrombin release pharmacokinetics, and in vitro clotting times of bound recombinant hiruwill be utilized to evaluate immobilized recombinant hirudin's thrombin binding and structural stabiprotein deposition on the material surface. The mechanical characteristics of the novel biomaterial