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International Journal of Bioprinting Three-dimensional bioprinting in toxicological research

Based on the previous research, mouse and human Chesne et al. created an organoid system using
organoid systems are promising models for therapeutic cryopreserved differentiated HepaRGs and human
applications and are more physiologically relevant than liver non-parenchymal fractions (NHS) in 1:2 ratio.
previous models, and they allow genome engineering and They exposed the cells with acetaminophen to simulate
manipulation of signaling pathways [7-9,34,48,58,60-77] . drug- DILI. They used fibrotic compounds, allyl alcohol

Organoids generated from tissue-resident stem cells and methotrexate, and observed that NHS is only activated
[77]
or progenitor cells derived from adult or embryonic in 3D co-cultures .
human tissue require special maintenance conditions. 8. 3D bioprinting
The cultivation of organoids must ensure that the
in vitro microenvironment is similar to the physiological 3D tissue printing is a dynamically evolving, computer-
attributions of the tissue; therefore, medium composition, controlled microarchitectural technology that uses living
physical environment, and hydrogel should be carefully cells, molecules, and biomaterials, called hydrogels, to
selected. By creating these conditions, multipotent create complex and functional tissue structures. 3D tissue
progenitors will be able to follow their own built-in program printing offers many opportunities for researchers in the
and self-organize into 3D organoid structures through field of regenerative medicine, as complete organs can
proliferation, and they must be similar to its origin tissue. be built layer by layer using raw biomaterials and living
Recent data show that primary cell-derived organoids cells directly from the patient. The complexity of different
are suitable for screening drug toxicity and studying tissues can also be excellently modeled using human-
molecular mechanisms of organ-specific functions, while derived cells and biomaterials, and the resultant model
stem cell-derived organoids can be applied as an effective can yield much more realistic responses in drug testing.
model for organogenesis and development. Organoids are Thus, 3D biofabrication undoubtedly outperforms the
appropriate for reproductive toxicology studies and more traditional 2D cultures [36,79-84] . A further advantage, in
suitable than animals in preclinical studies, because of addition to its structural features, is that different types of
interspecies differences [7-9,34,48,58,60-77] . To form organoids, tissue-specific cells can be incorporated into an artificial
progenitor cells and an extracellular matrix-like scaffold organ that function together, but can be in the same or
are needed to create a cell-cell and cell-matrix interactions. separate modular units, as in the case of the original
These interactions are essential for the cells to gain polarity organ. In addition to the presence of tissue-specific cell
and proper cell function, and after that, the concentration types, the role of the extracellular matrix can also be easily
gradient can be observed too (Figure 4) . mimicked, so that the cells are in the correct 3D position
[78]

Figure 4. Drug discovery and personalized medicine using organoids. Created with BioRender.com.

Volume 9 Issue 2 (2023) 203 https://doi.org/10.18063/ijb.v9i2.663