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International Journal of Bioprinting Bioprinted tissue-on-a-chip in drug screening

process was carried out under 37°C, meeting the drop-on-demand (DOD) inkjet bioprinting, categorized
requirement for cell survival without abrupt temperature into thermal bioprinting, piezoelectric bioprinting, and
change (Figure 3D). Chen et al. proposed a new method electrostatic bioprinting based on driving mechanisms,
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for mixing four materials in pairs in a complementary as shown in Figure 4A. Generally, natural bioinks with
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manner. One was composed of aldehyde hyaluronic acid low viscosity are suitable for inkjet-based bioprinting.
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(AHA)/N-carboxymethyl chitosan (CMC) bioink, which Stratesteffen et al. demonstrated that droplet-based
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rapidly gelled through Schiff base bonds. The other bioink bioprinting allowed the bioink to improve physiological
utilized here was the combination of gelatin and 4-arm relevance and the mechanical property simultaneously,
poly(ethyleneglycol) succinimidyl glutarate (PEG-SG), although the addition of collagen increased the viscosity of
connected by amide bonds. The addition of the latter the GelMA blend.
hindered the excessive fusion of the AHA/CMC bioink.
As a result, the four-component bioink could be directly Inkjet-based bioprinting can form tubular structures,
printed without extra crosslinking agents and exhibited but there have been no reports on 3D perfusable constructs
remarkable self-healing ability. using solely inkjet bioprinting because of the complex
production process and the ineligible quality of the hollow
3.2. Technical basis of bioink models: 3D bioprinting vessel tissue that fails to meet perfusion standards. However,
and microfluidic technologies inkjet bioprinting is well-suited for creating 3D organ or
When cell sources and biological materials are ready, the disease models and generating cell-embedded hydrogel
precision of model design and bioink delivery is determined blocks without intricate designs. Therefore, its advantages
by 3D bioprinting, which is an indispensable technological in precise cell delivery and creating homogeneous 3D
medium. The universal 3D bioprinting technologies and constructs have been extensively investigated, leading to
applications are presented in the following chapters. its wide application in high-throughput drug screening.
Twenty years ago, inkjet bioprinting was used to deliver Droplet-based bioprinting is good at maintaining cell
cell suspension as the bioink to the gel-based scaffolds, viability and precise deposition, but it fails in not only
setting a precedent for organ models produced rapidly and reproducing vascular filaments, but also restructuring the
repeatedly. Since then, multiple types of cells encapsulated integrity of tissue or organ microenvironments.
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in bioink can be printed to form 3D constructs, where the 3.2.2. Light-assisted bioprinting
bioink imitates the functions of ECM rather than a simple
support. Cultured models with pre-designed shapes, such Stereolithography (SLA) and digital light processing (DLP)
as organs or tissues, possess the interactions of cell–cell and bioprinting are two types of light-assisted bioprinting
cell–ECM and physiological characteristics, which allow for that use laser radiation to solidify the bioinks, improving
comprehensive understanding of the physiological models. efficiency, resolution, and repetitiveness in the fabrication
process. The laser beam controlled by computers scans
Vasculature is responsible for delivering nutrients the bioink, thereby realizing light curing of each layer
and removing metabolites in the human body. Although in constructs. During the construction of each layer
vascular endothelial cells are integrated, there are only structure, the preset pattern is solidified by the laser beam
disordered vessels without perfusion ability in some movement in SLA. DLP with higher efficiency can emit
3D-bioprinted vascular models. Attempts have been lights that disposably solidifies the bioink in each layer
made to mimic blood vessels using physical molds such throughout the entire construct (Figure 4B). Natural
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as microacupuncture needles, but the products in a single bioink has the risk of non-forming and excessive softness
form do not match the shape and structure of physiological in light-assisted bioprinting. Moreover, the introduction
vasculature. To overcome this, the combination of 3D of human-derived cells affects the viscosity and pellucidity
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bioprinting and microfluidic technology has emerged to of bioink. Bioinks, possessing functional groups that act
fabricate blood vessels with dynamic perfusion, thereby as crosslinks under light, should also exhibit acceptable
improving the culture efficiency. 91
mechanical properties and transparency. Although lights
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3.2.1. Droplet-based bioprinting at different wavelengths may be toxic to encapsulated
Inkjet-based bioprinting is a popular method for model cells, light-assisted bioprinting in tissue engineering
construction because of its precise deposition and low cell has been developed owing to its excellent resolution
damage. Bioink in droplet form is directly injected onto (10 μm). Similar to inkjet bioprinting, the fabrication of
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base materials, forming arrays or depositing in a layer- tube structures alone cannot completely replicate tissue
by-layer manner to create sandwich-like structures with microenvironments, even if perfusion capacity was not
functional cells. Inkjet-based bioprinting has advanced to taken into consideration.

Volume 10 Issue 3 (2024) 181 doi: 10.36922/ijb.1951