Biomimetic culture substrates for modelling homeostatic intestinal epithelium in vitro

Sorosh Abdollahi, Bahareh Zarin, Maryam Vatani, Fereshteh Vajhadin, Mohsen Hassani, Pezhman Jalali, Keekyoung Kim and Amir Sanati-Nezhad ()
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Sorosh Abdollahi: University of Calgary
Bahareh Zarin: University of Calgary
Maryam Vatani: University of Calgary
Fereshteh Vajhadin: University of Calgary
Mohsen Hassani: University of Calgary
Pezhman Jalali: University of Calgary
Keekyoung Kim: University of Calgary
Amir Sanati-Nezhad: University of Calgary

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract The increasing interest in utilizing three-dimensional (3D) in vitro models with innovative biomaterials to engineer functional tissues arises from the limitations of conventional cell culture methods in accurately reproducing the complex physiological conditions of living organisms. This study presents a strategy for replicating the intricate microenvironment of the intestine by cultivating intestinal cells within bioinspired 3D interfaces that recapitulate the villus-crypt architecture and 3D tissue arrangement of the intestine. Intestinal cells cultured on these biomimetic substrates exhibited phenotypes and differentiation characteristics resembling intestinal-specific cell types, effectively replicating intestinal tissue. Notably, tissue proliferation and differentiation were achieved within 72–120 h—significantly faster than the several weeks required by conventional bioengineered materials, which often pose risks of tissue necrosis or cross-contamination. Additionally, the differentiated cells on these villi-crypts mimicking bio-interfaces exhibit higher production of natural antimicrobial peptides, resulting in reduced pathogenic infection compared to control samples. Furthermore, our method stands out for simplicity in fabrication, eliminating the need for cleanroom procedures and complex microfabrication techniques.

Date: 2025
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DOI: 10.1038/s41467-025-59459-x

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