Emulation of Colonic Oxygen Gradients in a Microdevice

Abstract

Gut-on-a-chip in vitro modeling is an emerging field, as the human gut epithelium and gut microbiome have been recently identified as novel drug targets for a wide variety of diseases. Realistic in vitro gut models require a variety of precise environmental cues, such as chemical and gas gradients, in combination with substrates like mucus that support the growth of microbial communities. This technical brief describes a microfluidic architecture capable of developing a physiologically relevant oxygen gradient that emulates the oxygen profile proximal to the epithelial inner lining of the human colon. The device generates stable and repeatable defined oxygen gradients from 0% to 4 % partial pressure O over a length scale of hundreds of microns, and was applied to study the effects of oxygenation on the structure of native mucus that lines the colon wall. Using simulation as a design tool for hybrid gas-liquid microfluidic devices enables on-chip creation of defined, physiologically oxygen gradients. These microfluidic architectures have powerful potential applications for gut physiology, including providing optimal oxygenation conditions for the culture of mammalian epithelial cells in the gut lining, as well as creating a realistic mimic of the oxygen gradient found in the intestinal lumen for complex microbiome cultures.

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut

“…Organ-on-a-chip devices are microfluidic devices in which cells are cultured with organ-relevant spatiotemporal chemical gradients and dynamic mechanical cues, thereby aiming to reconstitute the structural tissue arrangements and functional complexity of living organs in vitro (154). Several gut-on-a-chip devices have already been developed (155)(156)(157)(158), only one in which multiple intestinal bacteria were successfully cultured (158). In this device, two channels simulating the gut lumen and a blood vessel are separated by a membrane coated with extracellular matrix and Caco-2 cells (158).…”

Everything You Always Wanted to Know About Organoid-Based Models (and Never Dared to Ask)

“… 90 , 164 , 113 These systems still are under improvement, but already can be exploited to recreate in vitro organ-specific features such as epithelium exposure to circulating fluid and flow-associated shear forces. 200 , 201 An increasing number of organs have been modeled using these systems as reviewed by Huh et al, 113 suggesting that such microfluidic systems could integrate several interconnected devices, each modeling a different organ (human-on-chip concept). This not only can permit cultures to be maintained for a length of time during experimentation, but also has been shown to lead to better maturation of the different cell types (co-)cultured.…”

Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

“…Several ‘gut-on-chip’ devices have been developed. 99 , 108–110 A gut-on-chip device consists of two channels simulating the gut lumen and a blood vessel, separated by an ECM-coated membrane and Caco-2 cells 99 [ Figure 1C ]. In contrast to static cell monolayers or organoids, fluid flow and peristalsis-like deformations applied to the epithelial layer stimulate Caco-2 cells to differentiate into the four different types of intestinal epithelial cells, and to organise in villus-like structures.…”