Human Colon Microphysiological System Reproducing Tissue Mechanical Microenvironment With Active Microfluidic Control and Imaging Capacity

Abstract

In vitro artificial colonic micro-devices that better replicate complex in vivo systems are essential tools for advancing our understanding of human gut (patho)physiology. Micro-physiological systems (MPS) offer controlled environments, enabling precise manipulation of tissue topography, rigidity and nutrient flow. We present the EnView system configured as a human colon-based MPS that faithfully replicates the 3D topography and matrix stiffness of the human colonic environment using an interpenetrating network of polyacrylamide and collagen I hydrogels, and enabling the culture of human colonic epithelium for weeks. The EnView system integrates a microfluidic chamber with active control of apical/luminal and basal/stromal compartments, allowing for in situ imaging and monitoring. Human colonic epithelial Caco-2 cells cultured up to 21 days in this system follow the crypt topography and formed a polarized epithelial monolayer. This innovative MPS recapitulates in vitro a human colon epithelium with its 3D matrix topology and stiffness control, integrates a microfluidic chamber allowing active control of the apical/luminal and basal/stromal compartments by accurate injection, as well as in situ imaging. TeaserHuman gut-on-chip reproducing tissue mechanical properties with active microfluidic control for 3D tissue characterization.