Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers

Abstract

Thin hydrogel barriers formed on the inner surface of injured arteries by interfacial photopolymerization dramatically reduced thrombosis and intimal thickening in rat and rabbit models of vascular injury. This polymerization technique allowed the synthesis of a thin hydrogel barrier that conformed to the vessel wall, directly blocking contact between blood and the damaged vessel. The illumination conditions could be varied to control the thickness of the barrier from 10 microns to > 50 microns. The hydrogel was designed to degrade by nonenzymatic hydrolysis. In rats in which the carotid artery had been severely injured by crushing, treatment with the hydrogel barrier completely eliminated thrombosis (P < 0.01) and preserved long-term patency (P < 0.01). Treatment in a rabbit model of balloon injury inhibited thrombosis (P < 0.02) and reduced long-term intimal thickening by approximately 80% (P < 0.003). These results suggest that blood-borne signals acting in the early phases of healing play an important role in stimulating thickening of the intima.