TY - JOUR
KW - Gastrointestinal models
KW - Tissue engineering
AU - Alican Özkan
AU - Gwenn E. Merry
AU - David B. Chou
AU - Ryan R. Posey
AU - Anna Stejskalova
AU - Karina Calderon
AU - Megan Sperry
AU - Joshua Piatok
AU - Viktor Horvath
AU - Lorenzo E. Ferri
AU - Emanuela Carlotti
AU - Stuart A. C. McDonald
AU - Douglas J. Winton
AU - Rocco Ricciardi
AU - Liliana Bordeianou
AU - Sean Hall
AU - Girija Goyal
AU - Donald E. Ingber
AB - Patients affected by inflammatory bowel disease (IBD) exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here we replicate these IBD hallmarks in human-derived organ-on-a-chip devices lined by colon epithelial cells from individuals with IBD when interfaced with matched fibroblasts, cultured under flow, exposed to peristalsis-like motions and perfused with circulating immune cells. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. In the IBD chip, inflammation and fibrosis are accentuated by peristalsis-like motions and, in female-derived chips, also by exposure to pregnancy-associated hormones. When exposed to carcinogens, the IBD chip shows increased inflammation, gene mutations and chromosome duplication, in contrast to healthy chips. These data suggest that the intestinal stroma, sex hormones and peristalsis-associated mechanical deformations have a key role in driving inflammation, fibrosis and disease progression in male and female individuals with IBD.
BT - Nature Biomedical Engineering
DA - 2026-05-21
DO - 10.1038/s41551-026-01686-8
LA - en
N2 - Patients affected by inflammatory bowel disease (IBD) exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here we replicate these IBD hallmarks in human-derived organ-on-a-chip devices lined by colon epithelial cells from individuals with IBD when interfaced with matched fibroblasts, cultured under flow, exposed to peristalsis-like motions and perfused with circulating immune cells. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. In the IBD chip, inflammation and fibrosis are accentuated by peristalsis-like motions and, in female-derived chips, also by exposure to pregnancy-associated hormones. When exposed to carcinogens, the IBD chip shows increased inflammation, gene mutations and chromosome duplication, in contrast to healthy chips. These data suggest that the intestinal stroma, sex hormones and peristalsis-associated mechanical deformations have a key role in driving inflammation, fibrosis and disease progression in male and female individuals with IBD.
PY - 2026
SP - 1
EP - 14
T2 - Nature Biomedical Engineering
TI - Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects
UR - https://www.nature.com/articles/s41551-026-01686-8
Y2 - 2026-05-21
SN - 2157-846X
ER -