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International Journal of Bioprinting 3D-printed NAFLD model

impacting hepatic detoxification capacity. The experimental a promising platform for in vitro drug screening and research
findings align with most of the literature reporting decreased on liver disease mechanisms, which contributes to a deeper
secretion of CYP450 enzymes in NAFLD patients, affecting understanding of NAFLD and facilitates the development
drug metabolism and excretion. 34 of related pharmaceuticals and therapeutic strategies.
Furthermore, in future studies, liver sinusoidal endothelial
3.5. 3D-printed NAFLD model application: cells, stellate cells, and Kupffer cells can be used to gain a
Prevention and reversibility more comprehensive understanding of NAFLD.
The 3D-printed NAFLD model was used for drug testing,
and ELA (a PPARα and PPARδ agonist) was selected Acknowledgments
due to its positive efficacy in both animal studies and in
vitro cell experiments. 35,36 The therapeutic effects of ELA None.
for the prevention and reversal of NAFLD were studied
in 3D-printed NAFLD models. For NAFLD prevention, Funding
ELA and lipogenic medium were added simultaneously This research was funded by the Natural Science Foundation
(Figure 5A). ELA (10 or 30 μM) was used to prevent NAFLD, of Hubei Province (grant number 2023AFB411) and the
and both ELA dosages had no significant effect on the cell Knowledge Innovation Project of Wuhan Science and
survival rate (Figure 5B), whereas 30 μM ELA prevented Technology Bureau (grant number 2023020201020532).
intracellular lipid accumulation (lipid accumulation was
close to that of the control group) (Figure 5C and D). For Conflict of interest
NAFLD reversal, lipogenic medium was added to induce The authors declare no conflicts of interest.
NAFLD, which was then replaced with medium containing
10 or 30 μM ELA to reverse NAFLD (Figure 5E). Moreover, Author contributions
10 and 30 μM ELA did not affect the cell survival rate
(Figure 5F), whereas 30 μM ELA reversed intracellular Conceptualization: Jing Liu
lipid accumulation (the lipid accumulation was close to Formal analysis: Tao Ding, Tianma He
that of the control group) (Figure 5G and H). Notably, ELA Investigation: Kun Du, Wei Peng, Zibei Ming
is a PPARα and PPARδ agonist that has beneficial effects Methodology: Feifei Pu, Ying Zhao, Renquan Ruan
on lipid metabolism according to the literature. 37,38 In this Writing – original draft: Kun Du, Wei Peng
study, ELA was used as an example to verify the feasibility Writing – review & editing: Jing Liu
of this platform for studying NAFLD drugs, suggesting
that both prevention and reversal of NAFLD could be Ethics approval and consent participate
replicated on the platform. Owing to the highly biomimetic Not applicable.
3D-printed liver tissue, physiologically similar physical and
chemical microenvironments, and more accurate NAFLD Consent for publication
modeling, the NAFLD model proposed in this study can
be used as a promising platform for in vitro drug screening Not applicable.
and liver disease mechanism research.
Availability of data
4. Conclusion Data is available from the corresponding author upon
In this study, a functional NAFLD model was successfully reasonable request.
constructed via 3D bioprinting technology. Large-scale
liver tissue with vascular-like functions was created in vitro References
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formation of bile canaliculi-like structures were also observed doi: 10.1016/j.jhep.2021.10.025
within it. The induced NAFLD model displayed significant 2. Sozen E, Demirel-Yalciner T, Sari D, Ozer NK. Cholesterol
lipid droplet accumulation in the NAFLD induction accumulation in hepatocytes mediates IRE1/p38 branch
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Volume 10 Issue 6 (2024) 370 doi: 10.36922/ijb.4312