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International Journal of Bioprinting Coronavirus-infected bioprinted intestine

3D bioprinting system was adapted to work with reduced a high-throughput organ-on-chip platform capable of
bioink volumes and environmental control, allowing the generating more complex tissue structures, with 96 chips
fabrication of cell-laden structures resembling the intestinal per platform, enabling real-time measurement of barrier
mucosa in a single printing step. The resulting intestinal function, oxygen concentration, and renal transport. 89
tissues closely mimic the 3D architecture of the small A pivotal advantage of 3D printing lies in its ability
intestine, including villi and crypts, with both the epithelial to create a wide array of high-throughput systems swiftly
and stromal compartments faithfully represented. These and automatically with varying designs. Mazrouei et al.
integrated intestinal models offer a promising platform demonstrated this potential by employing bioprinting
to study viral–host interactions, viral dynamics within to generate a range of custom-designed organ-on-chip-
the gut, and the influence of the gut microenvironment like platforms, integrating human colon cancer cells.
on viral infectivity and pathogenesis. With ongoing These platforms have proven effective for conducting 3D
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research and innovation in bioprinting technologies, the cell model analysis and exploring cellular responses to
field is continuously advancing to address challenges in therapeutic interventions (Figure 5A). Moreover, recent
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recapitulating the human intestinal system more accurately. advancements in bioprinting technology have paved the
Recently, tissue-specific biomaterials, such as colon- way for complete automation of the organ-on-chip process,
derived decellularized extracellular matrix (colon dECM), from fabrication to data analysis. To illustrate, Lind et
have been utilized in novel bioprinting strategies to create al. harnessed multi-material 3D printing to produce a
perfusable tubular models that spontaneously mimic the heart-on-chip system that incorporated a built-in sensor
3D morphogenesis of human intestinal epithelium. These for gauging the contractile strength of cardiac muscles.
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innovative bioprinted models offer an unprecedented Notably, the sensor itself was created via 3D printing
platform to study potential drug-induced toxicity on the during the fabrication phase. More recently, Trampe et
human intestinal tissue and to create co-culture models al. developed a bioink containing sensor nanoparticles
with commensal microbes and immune cells for future for monitoring oxygen in bioprinted cell-laden structures
therapeutic investigations. 83 (Figure 5B). These instances underscore the substantial
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potential of bioprinting technology in streamlining the
5.2. Bioprinted intestine-on-chip for high- creation of multifaceted devices encompassing cellular
throughput drug screening components and sensors. Ultimately, this progress holds the
High-throughput screening techniques are essential for promise of revolutionizing drug screening and advancing
drug development and discovery in the modern era. 84-87 coronavirus research through intestine-on-chip models.
Organ-on-chip technology has emerged as a powerful
tool for understanding human physiology and various 5.3. Studying multi-organ interactions using
diseases. While significant advancements have been made bioprinted intestine-on-chip
in the field, the advances in automating high-throughput The human intestine plays a pivotal role in upholding our
screening approaches in organ-on-chip models still lag well-being by serving as a vital communicator with distal
behind the developments of other in vitro models. This organs. For instance, perturbations in the integrity of the
is due to additional considerations such as device design, intestinal barrier have been linked to chronic liver disease,
fabrication, maintenance, and operation. diabetes, and obesity. Numerous diseases progress via
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Most studies utilizing organ-on-chip systems have intricate multi-organ interactions. Consequently, it is
focused on single or a few organ units per platform, plausible that an intestinal coronavirus infection could
limiting throughput. Fortunately, recent studies have potentially trigger aberrations in other organs.
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proposed scalable designs with increased throughput. The concept of multi-organ-on-chip (MOC) involves
Beaurivage et al. developed an intestine-on-chip model for the integration of cells from diverse organs or tissues
high-throughput disease modeling and drug discovery. within a single platform, thereby emulating multi-
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Their platform consisted of 40 individual intestine-on- organ interplay. Notable endeavors have employed such
chip units, each featuring three lanes of channels in platforms to replicate and study the impacts of intestinal
a single layer, with an intestinal tubule in the middle pathogens on interconnected organs. For instance, we
channel and two side media channels. Perfused culture have previously emulated kidney damage induced by shiga
was achieved through periodic tilting of the platform. toxin-producing E. coli through an intestine-kidney-on-
Additionally, an automated multichannel impedance chip setup. This design encompasses distinct intestine
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spectrometer designed for use with the platform measured and kidney modules, enabling an examination of antibiotic
transepithelial electrical resistance (TEER) at different time treatments’ effects on each organ during infection.
points. In a more recent study, Azizgolshani et al. created Leveraging the modular nature of this setup, our findings

Volume 10 Issue 2 (2024) 174 doi: 10.36922/ijb.1704