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

Background With the development of micromanufacturing and 3D printing technologies, gut-on-a-chip provides a new method for studying intestinal diseases in vitro. 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. Methods '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. Results 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 in vivo. Conclusions 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 in vitro detection to monitor real-time dynamics. Therefore, the gut-on-a-chip can serve as a powerful platform for studying IBD.