Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10160451 | Acta Biomaterialia | 2005 | 10 Pages |
Abstract
Using novel nitric oxide (NO)-generating polymeric hydrogels that can be rapidly photopolymerized in situ, we can deliver NO locally at the site of vascular injury. Depending on material design, these poly(ethylene glycol) (PEG)-based hydrogels can generate NO for up to 50 d. This study demonstrates the ability of nitric oxide-generating hydrogels (PEG-Cys-NO) to influence key components of the restenosis cascade both in vitro and in vivo. PEG-Cys-NO hydrogels inhibited smooth muscle cell proliferation, increased endothelial cell proliferation, and inhibited platelet adhesion in vitro. Moreover, in vivo, PEG-Cys-NO hydrogels inhibited intimal thickening in a rat carotid balloon injury model. The perivascular application of NO-generating polymers post-injury reduced neointima formation at 14 d by approximately 80% compared to controls (intimal area/medial area (I/M): PEG-Cys-NO = 0.20 ± 0.17, control = 0.84 ± 0.19, p < 0.00002; intimal thickness: PEG-Cys-NO = 12 ± 10 μm, control = 60 ± 18 μm, p < 0.00002). Treatment with the PEG-Cys-NO hydrogels caused a significant decrease in the per cent of proliferating cell nuclear antigen positive medial cells (29 ± 5%) at 4 d as compared to treatment with the control hydrogels (51 ± 1%, p < 0.02). Additionally, vessel re-endothelialization at 14 d was slightly enhanced in the presence of the NO-generating hydrogels. These data indicate that localized delivery of NO from these hydrogels can significantly inhibit neointima formation in a rat carotid balloon injury model and suggest that these materials may be useful in preventing restenosis.
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
Elizabeth A. Lipke, Jennifer L. West,