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International Journal of Bioprinting Coronavirus-infected bioprinted intestine

Figure 3. Advancing intestinal HCoV infection studies through intestine-on-chip models. (A) The intestine-on-chip platform cultivates gut epithelial cells
within dynamic environments, faithfully emulating the intricate conditions of the human gut in vivo. This setup integrates continuous perfusion, 3D villi
architecture, and chemical gradients (created with Biorender.com). (B) Leveraging these attributes, diverse scenarios of viral infection can be simulated,
offering insights into the complexities of infection dynamics (created with Biorender.com). Applications of intestine-on-chip for virus studies include (C)
the observation of apical polarization of Coxsackievirus B1 infection within the intestine-on-chip (reprinted under the Creative Commons CC0 public
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domain dedication), (D) recapitulation of the responses of intestinal epithelial and endothelial cells to SARS-CoV-2 infection (reprinted with permission
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granted by 2020 Science China Press; published by Elsevier B.V. and Science China Press), as well as (E) modeling and treatment of HCoV infection in
the gut using HCoV-NL63-infected intestine-on-chip setups (reprinted under the terms of the Creative Commons CC-BY license). 67
and function of the human intestine. These platforms the development of targeted strategies for prevention
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utilize microfluidic channels lined with intestinal epithelial and treatment.
cells and supporting cell types to recreate the complex One important consideration when establishing an
architecture and physiological conditions of the intestinal
tissue. By employing microfluidic-based systems, intestine- interaction model between the human intestine and
on-chip models offer several advantages. They can mimic pathogens on an intestine-on-chip is the 3D architecture
the dynamic flow of fluids, facilitate nutrient transport, present in the human intestine. The human intestine
and simulate peristalsis-like movements, providing a features villi structures, which are finger-like projections
more physiologically-relevant and controlled environment that increase the surface area of the intestinal epithelium
for studying the interactions between pathogens and to maximize nutrient absorption efficiency. 44,45 Between
gut epithelium. By recreating the microenvironment of each villus lies the crypt domain, which consists of multi-
the human intestine, intestine-on-chip models enable potent stem cells and Paneth cells; the other upper villi
the study of various aspects, such as pathogen entry, domains consist of other functionally differentiated
epithelial response, immune interactions, and potential epithelial cells, such as absorptive enterocytes, goblet cells,
therapeutic interventions. The ability to simulate these and enteroendocrine cells. 46,47 This differentiation between
interactions in a controlled and dynamic manner enhances the crypt and the tip of the villi leads to environmental
our understanding of intestinal infections and aids in variations that can affect pathogen–intestine interactions.

Volume 10 Issue 2 (2024) 170 doi: 10.36922/ijb.1704