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International Journal of Bioprinting Three-dimensional bioprinting in toxicological research

and their native microenvironment can also be mimicked. to expand and proliferate, while remaining stiff enough to
Thanks to the porous structures, blood flow can also be adhere during migration [10,47,83,85,86,88-90,96] . The blood vessels,
modeled, and even vascularized tissues can be built. The tubules and lumens found in organs are extremely difficult
success of implantation depends on many factors, but the to bioprint, but tissue mimicry will fail without these
most important include functionality, proper remodeling, structures. In the absence of channels, nutrients and oxygen
and a satisfactory host-graft response. In vivo research on could diffuse to a maximum of 200 μm, so it is not allowed
the effects of transplantable 3D biofabricated tissues on an to build larger structures. Bioprinting of organs with
individual is still ongoing, but by improving the method, it tubular structure, such as the kidney, is also challenging
will be possible in the future to replace damaged or missing for researchers. The tubular structure of the kidney allows
human organs with new ones that are not only functional, it to function properly, so the 3D structure has to resemble
but also able to cooperate with the human innate organs the original structure. Applying sacrificial hydrogels makes
too [5,9,10,83,85-92] . The development of preclinical models it possible for printing lumens and tubules, by filling the
suitable for toxicological tests is of particular importance interior of the lumen with liquefiable material that can be
(Figure 5). Finding the ideal model is essential for quickly washed out at the end of the printing process so as to leave
identifying novel medications with excessive toxicity at an empty tube [79,96,97] .
an early phase [10,82] . Since organs have complex structure,
spatial location and presence of cell types characteristic According to ISO/ASTM 52900:2015-12 Standard
of organs are essential for appropriate function. A lack of Terminology for Additive Manufacturing, there are three
categories of bioprinting, namely material jetting, material
proper 3D structure prevents the measurement of toxicity
because different medications may cause different reactions extrusion, and vat polymerization. This review provides
in different cell types [82,93] . The liver and kidneys play a a brief introduction of widely used bioprinting methods
[10,47,83,85,86,88-90]
central role in the elimination of drugs, but the skin is also (Figure 6) .
exposed to many toxic agents [10,82,94,95] . Characterizing their 8.1. Material extrusion
response to various drugs is essential for drug development
since systemic drug toxicity has a significant impact on these Extrusion techniques apply pneumatic or mechanic
organs. Modeling presents numerous challenges, including pressure to eject bioink through a nozzle. The pneumatic
the selection of appropriate spatial arrangement and cell approach uses air flow to compress bioink, while the
type as well as the selection of a suitable hydrogel. In many mechanic one works with axial piston to jet or form
cases, the hydrogel affects the cell viability, reproduction droplet. Both variants have one or multiple cartridges
rate, morphology, and spatial location. Therefore, the fixed on a moveable XYZ platform and a printing
selection of appropriate hydrogel is critical, because the surface. The design of parameters and printing process
cells need to be encased in a tissue-like, biocompatible are computerized, allowing printing of defined structure.
extracellular matrix that must be soft enough to allow cells Extrusion-based bioprinting is able to manage a variety of
hydrogels, high cell density, and constructs with complex
structure and composition. These features allow the
printing of heterogenic biomimetic structures; therefore,
this kind of technique is suitable for tissue/organ printing.
Further advantages, such as affordability, easy handling,
and commercial availability, make this technique the most
common printing method. The drawback of this technique
is that the high pressure causes shear stress effects on cells,
so the cell viability rate of this technique is lower than
that of the jetting techniques. Issues in nozzle clogging,
printing resolution, and speed could be a problem in
several cases [80,94,98,99] .
8.2. Material jetting
8.2.1. Inkjet bioprinting
Inkjet bioprinting could be divided into continuous, drop-
on-demand, and non-drop-on-demand inkjet bioprinting.
Figure 5. 3D models in toxicology testing. Created with BioRender.
com. 3D cell cultures can be developed for drug testing so as to allow the Since the continuous method is not used for bioprinting, it
selection of suitable medicine for patients. is omitted from discussion. One of the main advantages is

Volume 9 Issue 2 (2023) 204 https://doi.org/10.18063/ijb.v9i2.663