IDDF2024-ABS-0145 Microscale gut-on-a-chip system for disease modeling

<h3>Background</h3> With the development of micromanufacturing and 3D printing technologies, gut-on-a-chip provides a new method for studying intestinal diseases <i>in vitro</i>. Based on intestinal functions, gut-on-a-chip introduces modules with different parts, such as an injection pump for fluid flow and a pressure system for mechanical deformation. As a suitable platform for in vitro cell culture, microfluidic technology has attracted widespread attention in reconstructing various human organs, namely organ-on-a-chip technology. Compared to traditional model systems, gut-on-a-chip offers the capabilities of real-time observation, simulation of the intestinal microenvironment, adjustable fluid flow shear stress, and a host-microbiome interface. <h3>Methods</h3> ‘Gut-on-a-chip’ can be divided into three types based on its structure. The first type of gut-on-a-chip consists of an upper microchannel, a lower microchannel, and a porous membrane in between. The second type of gut-on-a-chip comprises an upper microchannel, a lower microchannel, and a middle channel. The third type of gut-on-a-chip consists of a left microchannel, a right microchannel, and a middle channel filled with collagen gel. To further enhance the gut-on-a-chip’s ability to mimic the in vivo microenvironment, cells with different functions, oxygen concentration gradients, and scaffolds are incorporated. <h3>Results</h3> Applied an optimized immune-related cytokine trigger that simulates the effect of Escherichia coli-activated dendritic cells on intestinal epithelial cells to mimic inflammatory characteristics in this model. Additionally, IECs derived from human intestinal organoids were integrated with monocyte-derived macrophages onto the gut-on-a-chip platform. Lipopolysaccharide and interferon-γ were used to induce IBD markers. Under microfluidic conditions, it was determined that the transcriptome of the gut-on-a-chip resembled that of a normal adult human colon <i>in vivo</i>. <h3>Conclusions</h3> Gut-on-chip can be employed to resolve many of these challenges by extracting key parameters to simplify the whole system, combining different modules to uncover interactions, and realizing <i>in vitro</i> detection to monitor real-time dynamics. Therefore, the gut-on-a-chip can serve as a powerful platform for studying IBD.