Bioengineered 3D tissue model of intestine epithelium with oxygen gradients to sustain human gut microbiome
Chen, Ying, Sara Rudolph, Brooke N. Longo, Fernanda Pace, Terrence Roh, Rebecca Condruti, Michelle Gee, Paula Watnick, and David L. Kaplan. 2022. “Bioengineered 3D Tissue Model of Intestine Epithelium with Oxygen Gradients to Sustain Human Gut Microbiome.” Advanced Healthcare Materials, June, 2200447. https://doi.org/10.1002/adhm.202200447.
The human gut microbiome is crucial to host physiology and health. Therefore, stable in vitro coculture of primary human intestinal cells with a microbiome community is essential for understanding intestinal disease progression and revealing novel therapeutic targets. Here, we present a three-dimensional (3D) scaffold system to regenerate an in vitro human intestinal epithelium that recapitulates many functional characteristics of the in vivo small intestine. The epithelium, derived from human intestinal enteroids, contains mature intestinal epithelial cell types and possesses selectively permeable barrier functions. Importantly, by properly positioning the scaffolds cultured under normal atmospheric conditions, two physiologically relevant oxygen gradients, a proximal-to-distal oxygen gradient along the gastrointestinal (GI) tract and a radial oxygen gradient across the epithelium, were distinguished in the tissues when the lumens were faced up and down in cultures, respectively. Furthermore, the presence of the low oxygen gradients supported the coculture of intestinal epithelial cells along with a complex living commensal gut microbiome (including obligate anaerobes) to simulate temporal microbiome dynamics in the native human gut. This unique silk scaffold platform may enable the exploration of microbiota-related mechanisms of disease pathogenesis and host-pathogen dynamics in infectious diseases including the potential to explore the human microbiome-gut-brain axis and potential novel microbiome-based therapeutics.View full article