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Bioprinting, microfluidics, and organoids to defeat COVID-19
morphology and functionality. For instance, cell-matrix interactions that are crucial in studying
Yanagi et al. developed an approach to fabricate COVID-19 pathogenesis.
liver-like tissues based on the fusion of the The most challenging aspect of designing
bioprinted spheroids [132] . In addition, Bhise et al. COVID-19 tissue platforms is modeling immune
designed a bioprinted liver-on-a-chip and showed response relevant for this disease . Hence, the
[2]
its full functionality for 30 days and sensitivity to “ideal” system should represent effects of dendritic
acetaminophen-induced toxicity [133] . cells and macrophages that secret inflammatory
The intestine is highly susceptible to the SARS- cytokines and chemokines (Interleukin [IL]-6,
CoV-2 infection because its epithelial cells express IL-8, IL-12, tumor necrosis factor-α, monocyte
ACE2 involved in amino acid homeostasis [134] . chemoattractant protein-1, Granulocyte-
[90]
Therefore, it is essential to include it as a target macrophage colony-stimulating factor, etc.) and
organ in the designed tissue model platform. cytotoxic T cells (CD4 and CD8 T cells). Hence,
+
+
There are numerous approaches for fabrication of two approaches might be applied. The first one
intestinal models, bioprinting is considered to be is designing immune-competent models [147,148] or
a promising approach [135] . Particularly, Madden integrated platforms by including lymph node
et al. showed that it is possible to fabricate a two- models [149,150] . The second approach is based on
layered construct consisting of epithelial cells the perfusion of immune cells suspension through
and myofibroblasts through bioprinting [136] . Such a chip.
construct had clear morphology, and cells expressed The integrated platform (Figure 3) includes
villin, E-cadherin, ZO-1, and enzymes and six target tissues/organs (nasal tissue, lungs,
proteins participating in xenobiotics metabolism heart, kidney, liver, and intestine), including
(cytochrome P450 2C9, multidrug resistance blood vessels. They connect to each other using
protein 1, breast cancer resistance protein, etc.) microfluidic channels ensuring virus transmission,
To mimic air and liquid flow for recapitulating cell supply with nutrients and oxygen, cell
the in vivo conditions, microfluidics can be migration, etc. Each particular model is
used as a tool. Such systems can be fabricated bioprinted to achieve native-like morphology and
using bioprinting [137-139] and have been already functionality. Bioink consists of cell (yellow) and
approved as both single organ (organ-on-a- hydrogel (blue) components and is tissue-specific.
chip) [131,140-143] and integrated (body-on-a-chip) The best option for a bioink cell component is
platforms [144-146] . Multi-organ model systems are organoids/spheroids as they can perform cell-cell
more physiologically relevant and permits better and cell-matrix interactions. To model immune
detection of complex virus-host effects than the first response, two approaches might be applied:
ones. Particularly, Maschmeyer et al. fabricated Designing immune-competent models/including
a four-organ-chip representing the intestine, the lymph node models into such integrated platform
liver, the skin, and the kidney [144] . Later, Vernetti and perfusing immune cells suspension through it.
et al. offered a more complex system reproducing
the microphysiology of coupled intestine, liver, 5 Conclusion
kidney proximal tubule, blood–brain barrier, and
skeletal muscle models [145] . However, there are To defeat COVID-19, the mankind should create
only several platforms which were fabricated new tools combining the emerging techniques
using bioprinting because the combination of these such as bioprinting, microfluidics, and organoid
emerging techniques is a relatively new approach. formation. To date, our understanding of the
For instance, Skardal et al. developed a three-tissue fabrication of tissue models for different viruses
system consisting of functional lung, cardiac, and and tissue engineering is growing, and they can
liver modules and proved its applicability for be applied in designing an integrated multi-tissue
drug testing [146] . Compared to such 2D models, bioprinted platform tailored for SARS-CoV-2
bioprinted models ensure complex cell-cell and infection. Despite that none has yet tested such

22 International Journal of Bioprinting (2020)–Volume 6, Issue 4