Abstract

A 3D functional human microvascular network in a microfluidic device was developed in this study. The established model enables endotheilal cells to form vessel-like microtissues and behave physiological functions which are closer to cells in human blood vessels. It provides a possible bridge for how the research outcomes translate to humans. The ɑ-MnO2 nanowires, which were successfully synthesized using the hydrothermal approach. The vascular toxicity was evaluated based on this organotypic 3D microvessel model. Our results demonstrated that ɑ-MnO2 nanowires can induce cytotoxicity in dose-dependently. Because the accumulation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are observed in the nanowire-treated cells. In addition, intravascular accumulation of ɑ-MnO2 nanowires could induce endothelial dysfunction by oxidative stress. This is expressed in disorder of NO expression and IL-6 up-regulation. Based on these results, we concluded that a mechanism for ɑ-MnO2 nanowire-induced vascular toxicity, which involves the accumulation of ROS, up-regulation of oxidative stress and inflammatory factors. This investigation may provide a fundamental insight to understand the nanotoxicity of wire-shaped nanomaterials.

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