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Related Experiment Video

Updated: May 17, 2026

Human Colonoid Monolayers to Study Interactions Between Pathogens, Commensals, and Host Intestinal Epithelium
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A collagen hydrogel-based intestinal model enabling physiological epithelial-immune cell interactions in host-microbe

Namju Kim1, Jiwon Kim1, Jonghoon Choi1,2

  • 1School of Integrative Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea.

Biomaterials Science
|June 6, 2025
PubMed
Summary

We developed InTRIC, a 3D intestinal model with immune cells and a biomimetic matrix, to study host-microbiota interactions. This advanced model better reflects gut conditions for drug discovery and microbiome research.

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Area of Science:

  • Biomedical Engineering
  • Immunology
  • Microbiology

Background:

  • Host-microbiota interactions in the human intestine are crucial but challenging to study due to complex cellular composition.
  • Existing models often fail to fully recapitulate the intricate interplay between intestinal epithelial cells and resident immune cells within their native microenvironment.

Purpose of the Study:

  • To develop and validate InTRIC (Intestinal model with Tissue-Resident Immune Components), a novel 3D intestinal model incorporating tissue-resident immune cells within a biomimetic extracellular matrix.
  • To assess the utility of InTRIC for studying host-microbiota interactions, including immune cell responses to bacterial stimuli and the impact of the microenvironment on epithelial-immune communication.

Main Methods:

  • Fabrication of a collagen-based hydrogel with controlled mechanical properties and minimal toxicity.
  • Integration of THP-1 derived macrophages and Caco-2 intestinal epithelial cells within the hydrogel to form a functional 3D intestinal model (InTRIC).
  • Exposure of the InTRIC model to commensal (Lacticaseibacillus rhamnosus) and pathogenic (Pseudomonas aeruginosa) bacteria to evaluate immune cell infiltration and cytokine secretion.

Main Results:

  • The InTRIC model successfully maintained THP-1 macrophage viability and differentiation, and formed a functional Caco-2 epithelium with appropriate barrier integrity (TEER values).
  • Exposure to P. aeruginosa significantly increased macrophage infiltration and IL-8 secretion compared to L. rhamnosus.
  • InTRIC demonstrated attenuated inflammatory cytokine secretion compared to conventional cocultures, highlighting microenvironmental modulation of immune responses. M2 macrophages showed altered IL-8 secretion patterns.

Conclusions:

  • The InTRIC platform provides a physiologically relevant 3D model for studying intestinal immune responses and host-microbiota interactions.
  • Incorporating immune cells and a biomimetic extracellular matrix is essential for accurately recapitulating intestinal conditions.
  • InTRIC offers a promising tool for drug discovery, toxicology, and microbiome research, enabling better prediction of in vivo responses.