Page 180 - IJB-10-2

International Journal of Bioprinting Coronavirus-infected bioprinted intestine

human coronaviruses, and highlight their potential for studied at the molecular level. Additionally, successful co-
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advancing our understanding of intestinal viral infections. culture systems of intestinal epithelial cells and microbiome
Furthermore, the abundance of coronavirus receptors in isolated from human stool samples have been established
the intestine facilitates the infection of other coronavirus using intestinal organoid-on-chip models. 80
strains. For instance, aminopeptidase N, the binding Given the limited availability of viral infection models
receptor for HCoV-229E, is abundantly expressed on using intestine-on-chip, particularly in the context of
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the microvilli of intestinal epithelium. Studies have human coronavirus infection, the integration of intestinal
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reported significantly increased aminopeptidase activity organoids with organ-on-chip technology presents
in intestine-on-chip conditions. 72,73 Hence, intestine- a promising opportunity (Figure 4). Notably, ACE2
on-chip models offer a robust platform for investigating expression has been shown to be significantly higher
the infection of various coronavirus strains. Further in intestine-on-chip models using intestinal organoid-
advancements in intestine-on-chip technology hold great derived primary cells than in 2D or initial organoid
promise for enhancing our understanding of intestinal cultures. Furthermore, the expression of the intestinal
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viral infections and aiding in the development of targeted stem cell marker leucine-rich repeat-containing G-protein
strategies for prevention and treatment. The integration coupled receptor 5 (LGR5) was found to be lower in the
of more complex physiological features and the ability to intestine organoid-on-chip condition than in 2D and
investigate viral behaviors and host–pathogen interactions initial organoid cultures. Therefore, culturing organoid-
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in a controlled and physiologically-relevant environment derived cells on intestine-on-chip is perhaps a more
offer valuable opportunities for studying intestinal viral accurate approach to modeling SARS-CoV-2 infection
infections in a more accurate and effective manner. in that ACE-2 expression and cell differentiation more
4.3. Intestinal organoid-on-chip for closely resembled the in vivo condition. Thus, intestinal
coronavirus research organoid-on-chip better replicates virus-binding receptor
Researchers have been exploring more advanced expression and cell differentiation observed in the in vivo
technologies to closely mimic in vivo organ environments. intestinal environment.
One promising approach is the combination of organoids
with organ-on-chip models, referred to as organoid-on- 5. Bioprinted intestine-on-chips for corona-
chip. Organ-on-chip platforms provide precise control virus research and drug screening
over the tissue microenvironment found in the human 5.1. Bioprinted intestine for coronavirus research
body, while organoids leverage the intrinsic developmental Bioprinting, a cutting-edge technology, allows the
programs of self-organizing stem cells to replicate the precise deposition of cells and biomaterials to create
key structural and functional properties of their in complex 3D tissue structures, closely mimicking the
vivo counterparts, including the formation of various native tissue architecture. In the context of studying
functionally differentiated cells specific to the organ of human coronaviruses, bioprinting offers a powerful
interest. This integration of organoids and organ-on- tool to replicate the complex microenvironment of the
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chip technology offers several significant advantages. human intestine, enabling more physiologically-relevant
Organoids, due to their stem cell maintenance, can be investigations into viral dynamics, host responses, and
expanded indefinitely, making them an invaluable source therapeutic interventions. For example, bioprinting has
of untransformed primary cells for organ-on-chip studies. 75 demonstrated great potential in generating 3D intestinal
Intestinal organoid-on-chip models have demonstrated models composed of human primary intestinal epithelial
significant potential in studying the human intestine. cells and myofibroblasts that exhibit polarized epithelium
Workman et al. demonstrated that it is feasible to culture with tight junctions, specialized epithelial cell types, and
intestinal organoid-derived cells on a micro-engineered functional cytochrome P450 (CYP450) enzymes. These
chip, which develops villi-like projections and elicits advanced 3D intestinal tissues develop physiological barrier
biological responses to inflammatory cytokines. function, distinguish between high- and low-permeability
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Kasendra et al. reported that organoid-derived cell culture compounds, and possess functional transporters for drug
on an intestine-on-chip more closely resembled the absorption and distribution. This model holds promise
transcriptomic profile of the in vivo intestine compared to in enhancing safety and efficacy prediction in drug
that of the initial organoid culture. This approach has also development, particularly for absorption, distribution,
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been employed to investigate intestinal metabolism and metabolism, and excretion (ADME)/toxicity studies. 81
drug transport. Moreover, the morphogenesis of villi-like One innovative approach employed an optimized
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projections in intestinal organoid-on-chip models has been
bioink formulation and printing parameters to produce

Volume 10 Issue 2 (2024) 172 doi: 10.36922/ijb.1704