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International Journal of Bioprinting Coronavirus-infected bioprinted intestine

Table 1. Summary of characteristics of cutting-edge in vitro intestine models
Model Cell source Standardized Physical features High Handling difficulty Cell Formation
initiation/ throughput differentiation of villi
culture protocol structure
Intestinal Primary cells, Well established 14 Presence of 3D Available 84 Relatively Possible 15,18 Self-formed 18
organoid stem cells 101 architecture, no easy (expect
perfusion 102 microinjection) 19,26,103
Intestine- Cell lines, Varies depending Presence of Available, Varies depending on Possible 50-55 Self-formed
on-chip primary cells, on chip design 104 perfusion, exposure depending on chip design 43 or
stem cells, to mechanical cues, chip design 87-89 artificially
organoid- presence of 3D formed 56,72
derived cells 43 architecture 102
Bioprinted Cell lines, Varies depending Diverse 3D Available 108 Difficult to optimize Possible 1,81,83 Artificially
intestine primary cells, on bioink structures and cell printing condition 105 formed 82,109
stem cells 1,81,83 composition compositions, wide
and bioprinting selection of materials
method 105 and printing
methods 106,107

In this paper, we emphasize the transformative with HCoV-229E, -OC43, -NL63, and -HKU1 have
potential of bioprinted gut chip models for understanding exhibited gastrointestinal symptoms. In a similar vein,
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viral infections and fortifying our arsenal against human another study highlighted that out of 47 patients with
coronaviruses. Starting with an overview of the human MERS-CoV, many reported symptoms like diarrhea (26%),
coronavirus, we review its intimate interactions with the vomiting (21%), and abdominal pain (17%). Furthermore,
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intestine. Subsequently, we evaluate contemporary in vitro it is noteworthy that the gut is not merely a site for
human intestinal models, focusing on the strengths and symptomatic manifestation but also plays a pivotal role
limitations of bioprinted iterations for studying enteric in the potential transmission of the virus. For instance,
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coronavirus (Table 1). Our narrative is structured to human coronaviruses, including the widely studied SARS-
illuminate current research gaps, which could be addressed CoV-2, have been identified in fecal samples, suggesting
through the advancements in bioprinted intestine- the presence of viable virus particles. This underscores
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on-chips. Ultimately, we envision that with continued the possibility that infected individuals can shed the virus
exploration, these models can be pivotal in reshaping our through their stool, which in turn raises concerns about
perception of gut-centric coronavirus infections, catalyzing transmission via the fecal-oral route, potentially through
the advent of innovative therapeutic solutions for global contaminated food, water, or surfaces, as illustrated in
public health. Figure 1.

2. Human coronaviruses Exploring the relationship between human
coronaviruses and the gut is critical because the gut
Coronaviruses are named for the crown-like spikes on microbiome and immune response have a major impact
their surface and belong to the family Coronaviridae. There on viral infection. For example, the gut microbiome can
are seven known strains of coronaviruses that can infect potentially influence the invasion and replication of SARS-
humans: human coronavirus-229E (HCoV-229E), HCoV- CoV-2 by downregulating angiotensin-converting enzyme
OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, Middle 2 (ACE2), a key regulator of innate immunity and the
East respiratory syndrome coronavirus (MERS-CoV), microbiome. 11-13 Such in-depth studies could contribute
and SARS-CoV-2. Some strains such as HCoV-229E are significantly to the development of targeted therapies,
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believed to cause the common cold and can cause mild to immunomodulatory approaches, and personalized
moderate respiratory illness, while some other stains such treatments, which are essential in the fight against viral
as SARS-CoV-2 can cause severe respiratory illness that diseases. In addition, understanding the role of the gut in
has led to a significant number of deaths worldwide. human coronavirus transmission and evolution has broad
Human coronavirus infections have been observed implications for vaccine effectiveness. Vaccines primarily
to manifest not just in respiratory symptoms, but also in target the spike protein of the virus, which is essential for
the gastrointestinal system. For instance, a significant respiratory infection, but investigating the involvement
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proportion, between 25% and 38%, of patients infected of the gut can provide insights into whether vaccines

Volume 10 Issue 2 (2024) 167 doi: 10.36922/ijb.1704