Nitric-oxide generating hydrogels inhibit intimal thickening and promote endothelial cell proliferation

Nitric oxide-generating hydrogels have been shown to inhibit smooth muscle cell proliferation and platelet adhesion, as well as promote endothelial cell proliferation; for this reason these hydrogels should be useful in preventing restenosis, or vessel re-occlusion, following balloon angioplasty. Over 600,000 percutaneous transluminal coronary angioplasty (PTCA) procedures are performed annually in the U.S.; unfortunately. 30-40% of patients treated with PTCA experience failure due to restenosis. We have developed nitric oxide (NO)-generating hydrogels that release NO over a period of days to weeks, depending on material design. They are able to significantly reduce platelet adhesion to collagen and inhibit smooth muscle cell proliferation in vitro. In addition, we have covalently grafted a cell adhesion peptide into the NO-generating hdrogels and assessed the ability of endothelial cells (EC) to proliferate on the surface. ECs owed significantly higher rates of proliferation on the NO-generating hydrogels as compared to controls. The perivascular application of NO-generating, hydrogels significantly reduced neointimal formation in an experimental balloon angioplasty model as compared to controls. The combined effects of these NO-generating hydrogels make them well suited for incorporation into blood-contacting devices and for use as a stent coating or stent replacement to prevent restenosis following balloon angioplasty.