Nitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation

We have developed polymeric biomaterials capable of providing localized and sustained production of nitric oxide (NO) for the prevention of thrombosis and restenosis. In the current study, we have characterized the kinetics o f NO production by these materials and investigated their efficacy in reduc ing platelet adhesion and smooth muscle cell proliferation in vitro. Three nitric oxide donors with different half-lives were covalently incorporated into photopolymerized polyethylene glycol hydrogels. Under physiological co nditions, NO was produced by these hydrogels over periods ranging from hour s to months, depending upon the polymer formulation. NO production was inhi bited at acidic pH, which may be useful for storage of the materials. The N O-releasing materials successfully inhibited smooth muscle cell growth in c ulture. Platelet adhesion to collagen-coated surfaces was also inhibited fo llowing exposure of whole blood to NO-producing hydrogels. The effects of N O production by these hydrogels on platelet adhesion and the proliferation of smooth muscle cells suggest that these materials could reduce thrombosis and restenosis following procedures such as balloon angioplasty. (C) 2000 Elsevier Science Ltd. All rights reserved.