Microvessel-on-Chip Fabrication for the in Vitro Modeling of Nanomedicine Transport

Abstract

Tumor-on-chip devices are becoming ideal platforms to recreate in vitro the particular physiological microenvironment of interest for onco-nanomedicine testing and development. This work presents a strategy to produce a round artificial microvessel on-a-chip device for the study of physiologically relevant nanomedicine transport dynamics. The microchannels have a diameter in the range of the tumor capillaries and a semicircular geometry. This geometry is obtained through an intermediate thermal nanoimprint step using a master mold with square-shaped channel structures produced by standard silicon micromachining or by stereolithography three-dimensional (3D) printing. The working microfluidic chip devices are made by casting polydimethylsiloxane on the imprinted intermediate mold. Artificial blood microvessels are created by seeding human endothelial cells into the round-shaped channels acting as the scaffold. The microchip is connected by 3D-printed reservoirs to a pressure controller, allowing for a fine fluidic control. Under physiological flow conditions, the dynamic interaction of nanoparticles (NPs) with the artificial endothelium was assessed by high-magnification fluorescence microscopy. Overtime, internalization of NPs and clustering was observed and the accumulation rate into the endothelial cells could be characterized in real time.