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International Journal of Bioprinting 3D bioprinting for translational toxicology

In the domain of food safety, Chandiramoha et al. highlighting the model’s superior replication of in vivo NP
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utilized 3D printing technology to create an in vitro exposure exposure responses. The study highlighted the numerous
system (IVES) to simulate the physiological effects of advantages of 3D bioprinting in nanotoxicology research,
cannabis inhalation on the lungs. The system was designed including the creation of physiologically relevant models,
to load epithelial cells and expose them to cannabis smoke enhanced NP diffusion and cellular interactions, and
to mimic pulmonary responses to inhaled substances. more realistic toxicity assessments. These findings suggest
The team fabricated a lung-like four-chamber IVES that 3D bioprinting could become a pivotal tool in future
using 3D printing, featuring two inlets, four outlets, and nanotoxicology and nanomedicine research, providing a
four chamber lids, effectively simulating the “inhalation” reliable and ethical alternative to traditional methods while
process and distributing smoke to four cell-filled chambers adhering to the 3R principles in toxicological studies.
before expelling it. During experiments, research-grade
cannabis was ignited, with smoke introduced into the IVES 4.4. Cardiovascular toxicology
via a three-way valve and syringe. Following simulated The heart, as a key target organ for the toxicity of exogenous
inhalation, the researchers assessed epithelial cell viability chemicals, is crucial in drug toxicology research. Zhang
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and immune function, finding a marked impairment of et al. developed an innovative approach utilizing 3D
cellular immunity. Results revealed that cannabis use bioprinting technology to construct endothelialized
could induce symptoms such as coughing, wheezing, myocardial and heart-on-a-chip models. Using composite
and chest tightness. By comparing cytokine levels in the bioinks, the researchers created microfibrillar hydrogel
IVES with those extracted from individuals with smoking- scaffolds via 3D bioprinting and directly incorporated
related disorders, the study underscored the heightened endothelial cells into these scaffolds. Over time, the
susceptibility of recreational cannabis users to throat endothelial cells migrated to the periphery of the
inflammation and other respiratory issues. These findings microfibers, establishing a continuous endothelial layer.
hold particular relevance in the context of cannabis Subsequently, cardiomyocytes were seeded onto these 3D
legalization for medical use. The study also emphasized endothelial beds, resulting in organized myocardial tissues
the potential of 3D printing technology in toxicological that exhibited spontaneous and synchronous contraction.
research, including aerosol analysis, pathogen impact These organoids were embedded into specially designed
evaluations, and immune system studies. microfluidic perfusion bioreactors, thereby completing the
endothelialized myocardial platform for cardiovascular
In material toxicology, Gerbolés et al. investigated the toxicity evaluation. Using doxorubicin—a common
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application of 3D bioprinting in fabricating organoid-based anticancer drug—as a test case, the endothelialized
scaffolds for long-term NP toxicity studies. This approach myocardial tissue chip model was evaluated for its
aimed to better simulate lung cell exposure to NPs, cardiovascular toxic response to the drug. Results showed
providing a more accurate model compared to traditional that upon exposure to 10 and 100 mM doxorubicin,
2D cell cultures. Using a customized 3D bioprinter, the cardiomyocyte contraction rates decreased to 70.5% and
researchers fabricated viscous hydrogels containing cells, 1.62%, respectively. Constructs exposed to 10 and 100
composed of alginate, gelatin, and Matrigel, optimized to mM doxorubicin exhibited reductions in von Willebrand
support cell viability and structural integrity. Immortalized factor levels secreted by endothelial cells to 76.0% and
lung cell lines were cultured within the bioprinted scaffolds 35.3%, respectively. These findings demonstrate that the
over extended periods to examine interactions with NPs, endothelialized myocardial tissue chip model effectively
including 40 nm fluorescent latex particles and 11–14 nm simulates the dose-dependent toxic effects of doxorubicin
silver NPs. Results revealed enhanced cell proliferation on cardiomyocytes and endothelial cells, providing
within the 3D scaffolds, with cell numbers increasing from potential applications for personalized drug screening and
5 × 10 to 1.27 × 10 over 14 days, indicating an optimal mitigating drug-induced cardiovascular toxicity.
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environment for cellular growth. Lipid peroxidation levels
decreased by 91%, indicating reduced oxidative stress, a Concurrently, Yong et al. created a biohybrid 3D
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common response to NP exposure. Additionally, the 3D printing method to fabricate a tissue-sensor platform,
environment demonstrated minimal cell death over 21 as shown in Figure 7E. This platform consists of an
days, underscoring the protective nature of the bioprinted engineered heart tissue (EHT) integrated with dual-
scaffolds. NP diffusion within the 3D scaffolds was another column-grafted strain gauge sensors, facilitating wireless,
critical observation, with fluorescent NPs permeating real-time, and continuous monitoring of drug-induced
the scaffold, effectively replicating in vivo conditions. cardiotoxicity. Through a one-step printing process,
Compared to 2D cultures, cells exposed to silver NPs in researchers produced integrated 3D EHT and strain
the 3D model displayed significantly higher survival rates, gauge sensors utilizing five distinct inks. By printing two

Volume 11 Issue 4 (2025) 119 doi: 10.36922/IJB025210209