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Updated: Aug 27, 2025

Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality
Published on: May 5, 2022
Modeling mucus physiology and pathophysiology in human organs-on-chips
Zohreh Izadifar1, Alexandra Sontheimer-Phelps1, Bob A Lubamba1
1Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, United States.
Abstract:
The surfaces of human internal organs are lined by a mucus layer that ensures symbiotic relationships with commensal microbiome while protecting against potentially injurious environmental chemicals, toxins, and pathogens, and disruption of this layer can contribute to disease development. Studying mucus biology has been challenging due to the lack of physiologically relevant human in vitro models. Here we review recent progress that has been made in the development of human organ-on-a-chip microfluidic culture models that reconstitute epithelial tissue barriers and physiologically relevant mucus layers with a focus on lung, colon, small intestine, cervix and vagina. These organ-on-a-chip models that incorporate dynamic fluid flow, air-liquid interfaces, and physiologically relevant mechanical cues can be used to study mucus composition, mechanics, and structure, as well as investigate its contributions to human health and disease with a level of biomimicry not possible in the past.
Insights
New organ-on-a-chip models create realistic mucus layers for studying human health and disease. These microfluidic devices offer unprecedented biomimicry for investigating mucus biology and its role in various organs.
Area of Science:
- Biomedical Engineering
- Mucosal Immunology
- Microfluidics
Background:
- Mucus layers protect human organs but studying their biology is difficult due to limited in vitro models.
- Disruption of the mucus layer is linked to disease development.
Purpose of the Study:
- To review advancements in organ-on-a-chip microfluidic models for studying human mucus.
- To highlight the application of these models for lung, colon, small intestine, cervix, and vagina.
Main Methods:
- Development of microfluidic culture systems that mimic human organ epithelial barriers and mucus layers.
- Incorporation of dynamic fluid flow, air-liquid interfaces, and mechanical cues.
Main Results:
- Organ-on-a-chip models successfully reconstitute physiologically relevant mucus layers.
- These models enable detailed study of mucus composition, mechanics, and structure.
Conclusions:
- Organ-on-a-chip technology provides a powerful, biomimetic platform for advancing mucus biology research.
- These models are crucial for understanding mucus's role in health and disease across multiple human organs.

