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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

the 3D-bioprinted model allows for the creation of more focused on assessing the dose-dependent toxicity of CuO
physiologically relevant structures, which can provide NPs by examining cell viability, contractile function,
more accurate assessments of drug effects. and gene expression related to mitochondrial biogenesis

The authors also demonstrated the induction of a and apoptosis pathways. The 3D bioprinting process was
colitis-like condition in their 3D-printed model by treating used to construct cardiac microtissues that closely mimic
it with dextran sodium sulfate (Figure 7A). Histological the structural and functional properties of human heart
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analysis showed significant epithelial disorganization, tissue. The bioprinted tissues included iPSC-derived
indicative of colitis, thereby validating the model’s ability cardiomyocytes and human cardiac fibroblasts, creating a
to mimic disease conditions accurately. This is crucial complex tissue environment. CuO NPs were coated with
for studying the efficacy of anti-inflammatory drugs in a bovine serum albumin to simulate protein adsorption
controlled, reproducible environment. Furthermore, the in vivo, which stabilizes the NPs and enhances the
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study compared the barrier function of the 3D-printed reliability of experimental results. CuO NP exposure
constructs with traditional 2D monolayer cultures. The resulted in significant cytotoxicity in the bioprinted
transepithelial electrical resistance (TEER) measurements cardiac tissues. Viability assays indicated a median lethal
revealed that the 3D-printed models provided more dose (LD ) of 7.176 µg/mL, with complete cell death
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reliable data on barrier function, maintaining higher observed at 100 µg/mL. Notably, the contractile force of
physiological relevance over time compared to 2D cultures the tissues significantly decreased at 10 µg/mL after 48
(Figure 7B). This is a significant finding, as barrier integrity hours, highlighting the impact of CuO NPs on cardiac
is a critical factor in evaluating the therapeutic potential of function. Interestingly, the beating frequency of the tissues
anti-inflammatory drugs. The researchers also assessed the was not significantly affected up to the 10 µg/mL dose,
impact of albumin nano-encapsulated drugs, specifically suggesting that the electrical signaling pathways related to
roxadustat and caffeic acid phenethyl ester, on the barrier contraction remained intact at lower NP concentrations.
function of the 3D-printed colitis model. They observed Gene expression analyses provided further insights into
that these nano-encapsulated drugs were effective in the mechanisms of CuO NP toxicity. The study found
maintaining barrier integrity, as indicated by stable TEER dose-dependent increases in markers of mitochondrial
values. This suggests that the 3D-printed model can biogenesis, such as peroxisome proliferator-activated
be an effective tool for evaluating the efficacy of nano- receptor gamma coactivator 1-alpha (PCG-1α) and
encapsulated therapies, which are increasingly important NADH dehydrogenase 1 (NDI), indicating mitochondrial
in the treatment of inflammatory diseases. 101 damage. Additionally, significant upregulation of caspase
3 and caspase 8 suggested that apoptosis in the cardiac
8. Three-dimensional bioprinted tissues was mediated primarily through the extrinsic death
toxicity models receptor pathway. The use of 3D-bioprinted cardiac tissues
offers several specific advantages over traditional models.
Understanding the toxicity of NPs is crucial to ensuring For example, it allows for more accurate replication of
their safe application in biological systems. 102–104 Toxicity cell-cell and cell-matrix interactions, providing a realistic
studies investigate how NPs interact with cellular assessment of cellular behavior and response. Additionally,
environments, affecting cell survival, proliferation, and the integration of force measurement capabilities enables
function. Nanoparticle toxicity can lead to cell damage, direct evaluation of changes in tissue contractility, which
inflammatory responses, and long-term biocompatibility is crucial for understanding the impact of toxicants on
issues. 105–107 Three-dimensional bioprinting technology cardiac health. Miller et al.’s study presents significant
offers a novel method for toxicity evaluation by mimicking methodological advancements in utilizing bioprinting
more realistic tissue structures compared to traditional technology to evaluate NP toxicity. This approach provides
2D cultures. This approach allows for a more accurate a robust tool for precisely assessing the effects of NPs on
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analysis of the long-term effects and bioaccumulation human tissues and establishes a solid foundation for future
of NPs. 109,110 toxicological research. 112
8.1. Three-dimensional bioprinted human 8.2. Organoid-based bioprinting for toxicological
cardiac tissue model for evaluating copper oxide evaluation of silver nanoparticles
nanoparticle toxicity Gerbolés et al. studied the application of 3D bioprinting to
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The study by Miller et al. utilized advanced bioprinting create organoid-based scaffolds for long-term toxicological
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technology to create human-induced pluripotent stem investigations of NPs (Figure 8). This approach aims to
cell (iPSC)-derived cardiac microtissues for evaluating simulate the exposure of lung cells to NPs, providing
the toxicity of copper oxide (CuO) NPs. This research a more accurate model for nanotoxicological studies

Volume 10 Issue 5 (2024) 19 doi: 10.36922/ijb.4273