The behavior of endothelial cells on polyurethane nanocomposites and the associated signaling pathways

A Series of nanocomposites from polyurethane (PU) incorporated With various low concentrations ( 17.4-174 ppm) of gold nanoparticles (approximately 5 nm) (denoted "PU-Au") were Used as a model system to Study the mechanisms that influenced endothelial cell (EC) migration oil biomaterial Surfaces. The migration rate of ECs oil the PU-Au nanocomposites was determined by a real-time image system. It was found that ECs had the highest migration rate oil the nanocomposite containing 43.5 ppm of gold ("PU-Au 43.5 ppm"). The high EC migration rate was associated with increased levels of endothelial nitric oxide synthase (eNOS) and phosphorylated-Akt (p-Akt) expressed by ECs cultured oil PU-Au The inductions Of both eNOS and p-Akt oil PU-Au were abolished by the addition of LY294002 (PI3K inhibitor), Suggesting that these cellular events may be regulated through the PI3K signaling pathway. Using a biotinylated VEGF-165 that recognizes VEGF receptors and by FACS analysis, slightly higher expression of VEGF receptors for ECs oil PU-Au was also demonstrated. Phalloidin staining showed that actin appeared as a circumferential band Surrounding each cell oil tissue Culture polystyrene, whereas oil PU-Au, especially oil PU-Au 43.5 ppm, the cells had their margin spread out and extend processes with stress fibers in the protruding lamellipodia. Moreover, the higher EC migration rate oil PU-Au 43.5 ppm Was Suppressed by LY294002. The higher protein expression of focal adhesion kinase (FAK) oil PU-Au 43.5 ppm was observed in FAK-GFP transfected ECs. It was concluded that PU-Au nanocomposites activated FAK and the PI3K/Akt signaling pathway in ECs, leading to proliferation and migration of ECs on these Surfaces. (C) 2008 Elsevier Ltd. All rights reserved.