Abstract

Development of Novel Intestine-on-Chip Models

Nancy Allbritton, Frank and Julie Jungers Dean of the College of Engineering and Professor of Bioengineering, University of Washington in Seattle

Organ-on-chips are miniaturized devices that arrange living cells to simulate functional subunits of tissues and organs. These microdevices provide exquisite control of the biochemical and biophysical microenvironment for the investigation of organ-level physiology and disease. 2D and 3D models displaying a polarized human colonic epithelium were developed to recapitulate gastrointestinal physiology. The 2D crypt mimic displays a spatially patterned monolayer of epithelium displaying a stem-cell niche and differentiated cell zone with cells migration between the two regions. This planar 2D format enables efficient image cytometry for high-throughput screening applications as well physiologic measurements difficult to perform in a 3D format e.g., calcium signaling measurements. The 3D model builds on the 2D model by providing the full architecture of the in vivo human crypt. These models support formation of gradients of growth factors, microbial metabolites, and gases. A thick impenetrable layer of mucus with biophysical parameters similar to that of a living human can be formed for epithelial cell-microbe studies. These bioanalytical platforms are envisioned as next-generation systems for assay of microbiome-behavior, drug-delivery, and toxin-interactions with normal and diseased intestinal epithelia.