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Bioprinting, microfluidics, and organoids to defeat COVID-19
cirrhosis and hepatocellular carcinoma . Cell 3.3 Herpesviruses
[64]
polarity and micro-environmental complexity
and interactions are absent in 2D culture systems. Epithelial tissue is the initial site of infection for
Due to the drawbacks of 2D model systems, most herpesviruses. Although they cause latent
researchers are looking for alternative 3D models. infection mainly in neurons, they are still able to
The establishment of 3D models including infect other cells. Therefore, there are numerous
spheroids, organoids with multi-cellular structures, tissue models available, which include various
and their specific extracellular matrix (ECM), cell types to study this virus group. For example,
was shown to exhibit higher tissue-specific Tajpara et al. developed a model based on the
environmental complexity, more mature cells, microneedle-pretreated human abdominal skin
and better physiological functionality compared explant to test antivirals and their combinations
[67]
to simple 2D counterparts. For instance, several against human simplex virus (HSV-1) infection .
studies established liver spheroid models to study Zhu et al. fabricated 3D air-liquid interface
the hepatotrophic virus lifecycle in liver tissue. culture consisting of human normal vaginal
Chong et al. generated primary human hepatocyte epithelial cells to describe viral transmission of
[68]
spheroids from uninfected liver resections and HSV-2 and related pathological changes . To
inoculated the spheroids with HCV-positive study viral effects on neural tissue and acyclovir
serum . Data showed that spheroids have efficacy, D’Aiuto et al. proposed a scaffold-free
[65]
differentiated phenotype and expressed putative 3D hiPSC-based neuronal model and showed
HCV receptors; the HCV RNA was detected that the IC50 of acyclovir in 2D cell cultures was
[69]
in the cells as well as supernatant of culture lower than that in 3D culture . Sison et al. also
media . Moreover, Nie et al. used a coculture used iPSCs to fabricate cortical organoids to study
[65]
system of human induced pluripotent stem cell human cytomegalovirus infection and revealed
(hiPSC)-derived endoderm, human umbilical the organoid structure disruption and alterations
[70]
vein endothelial cells, and mesenchymal stem in specific markers expression .
cells in a 3D microwells to assess the potential 3.4 HIV
of liver organoids for HBV infection and virus-
host interactions . The cells self-organized and HIV infection is one the most difficult infections
[66]
differentiated into the functional liver organoids. to study due to high selectivity and host specificity.
Then, organoids were infected with the HBV HIV mainly infects immune cells, and the recent
genome. The liver organoids exhibited more study has offered a novel efficient 3D model based
[52]
functionality and higher susceptibility to HBV on CD4+ T-lymphocytes . By varying density of
infection compared to human iPSC-derived 2D collagen gel embedding cells, Imle et al. evaluated
hepatic-like cells. These organoids could sustain the virus transmission and revealed that it can be
HBV propagation and produce infectious virus up to significantly influenced by 3D environment.
20 days. HBV infection decreased the expression of
hepatic-specific genes and increased the expression 4 Designing an “ideal” tissue model to study
of early biomarkers for acute liver failure, alanine SARS-CoV-2 infection
aminotransferase, and lactate dehydrogenase in the 4.1 Models and their limitations
supernatant of infected organoids. The advantage
of hiPSC-derived 3D liver organoids was that To date, there is only a limited number of models
they provided HBV infection models for precision available to study the SARS-CoV-2 infection.
medicine . In addition, other cell culture models The most susceptible animals to this coronavirus
[66]
including, specific scaffold embedded cells and are ferrets [3,4] , cats , and rhesus and cynomolgus
[4]
single-channel microfluidic devices are promising macaques [5,6] . The latter is considered to be a
platforms in vitro models to study hepatotropic rapidly established SARS-CoV-2 model without
viruses . any additional modifications . Rhesus macaques
[63]
[6]
18 International Journal of Bioprinting (2020)–Volume 6, Issue 4