Guidance of liver and kidney organotypic cultures inside rectangular silicone microchannels

Abstract

We have studied the effect of rectangular polydimethylsiloxane (PDMS) microchannels on the behavior of embryonic liver and kidney explants maintained in contact with these microchannels. The microchannel widths were varied from 35 to 300 μm and depth from 45 to 135 μm. The growth of these tissue types were compared to the development on flat silicone and plastic control material. At seeding, due to the viscoelastic properties of both organs, “capillary-like filling” was observed inside the narrowest microchannels. In those cases, the tissues grew to a confluent layer joining the microchannels with no cell migration and proliferation inside the microchannels. In the largest microchannels, only a weak migration was observed and the cellular behavior appears quite similar to that of PDMS flat culture conditions. In intermediate geometries, we observed different tissue growth properties inside the microchannels when compared to other sizes. The liver tissues progressed inside those microchannels with an average growth velocity of up to 72 μm/dayresulting to form a dense three-dimensional multicellular ‘liver-like tissue’. Scanning electron microscopy (SEM) observations demonstrated that the tissue was organized like an epithelial layer with round cells embedded in an extracellular matrix. Liver cell mobility may result primarily from the activity of the marginal cells, whereas the submarginal cells appeared passively dragged. Parenchymal organization demonstrating differentiated states was also observed. Kidney grew mainly on the microchannel walls and the tissues never appeared dense and organized as the liver ones.