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Bioprinting of a Hepatic Tissue Model
has potential applications in in vitro toxicological studies. Department of Health (YKK19070), the Fundamental
However, further investigation into this methodology Research Funds for the Central Universities (0214-
is needed. The mechanical strength of alginate-gelatin 14380510), the Nanjing health science and technology
bioink is relatively weak and incapable of supporting development project for Distinguished Young Scholars
long-term cultures; therefore, bioink components should (JQX19002), Project of Modern Hospital Management
be optimized to achieve better mechanical properties and and Development Institute, Nanjing University and
favorable biofunctionality. In addition, the co-culture of Aid project of Nanjing Drum Tower Hospital Health,
hiPSC-Heps with non-parenchymal hepatic cells, such Education & Research Foundation (NDYG2020047),
as mesenchymal stem cells , fibroblasts , vascular fundings for Clinical Trials from the Affiliated Drum
[52]
[51]
endothelial cells , stellate cells , and Kupffer cells , Tower Hospital, Medical School of Nanjing University
[53]
[55]
[54]
should be incorporated into the 3DP hepatic tissue model to (2021-LCYJ-PY-46), the Chen Xiao-ping Foundation for
more accurately mimic the cellular microenvironment of the Development of Science and Technology of Hubei
liver tissue. Furthermore, investigation of hepatotoxicity Province, China (CXPJJH121001—2021073).
induced by other types of drugs, such as antituberculotic
and antineoplastic drugs, should be considered in this Conflict of interest
3DP model. The authors declare that the research was conducted in
the absence of any commercial or financial relationships
5. Conclusion that could be construed as a potential conflict of interest.
A hepatic tissue model was constructed by 3D bioprinting Author contributions
hiPSC-Heps using an alginate-gelatin bioink. Compared
with the non-printed SW model, the hiPSC-Heps in the Research, writing, editing and formatting of the
3DP model formed 3D spheroids with higher overall manuscript: JH, JW, and HR; Data collection and
viability and proliferation. The hiPSC-Heps in the SW analysis: HY and KS; Administrative support and funding
and 3DP models showed upregulated mRNA expression acquisition. YP, XQ, TX and HR. All authors contributed
of liver function-related biomarkers compared to those in to the article and approved the submitted version.
the 2D model. The secretion of AAT, albumin, and BUN
was found to be highest in the 3DP model of the three References
models, indicating the well-maintained biofunctions of
hiPSC-Heps using this method. In the drug testing of 1. Agarwal T, Banerjee D, Konwarh R, et al., 2021, Recent
APAP-induced hepatotoxicity, the 3DP model exhibited Advances in Bioprinting Technologies for Engineering
favorable performance with the upregulation of the drug Hepatic Tissue. Mater Sci Eng C Mater Biol Appl, 123:112005.
metabolic enzyme CYP1A2. This 3DP model could be https://doi.org/10.1016/j.msec.2021.112013
used as an advanced hepatic tissue model for potential 2. Hwang DG, Choi YM, Jang J, 2021, 3D Bioprinting-Based
applications in in vitro toxicological studies. Vascularized Tissue Models Mimicking Tissue-Specific
Acknowledgments Architecture and Pathophysiology for In Vitro Studies. Front
Bioeng Biotechnol, 9:685507.
None.
https://doi.org/10.3389/fbioe.2021.685507
Funding 3. Ma L, Wu YT, Li YT, et al., 2020, Current Advances on
3D-Bioprinted Liver Tissue Models. Adv HealthcMater,
This work was supported by the National Natural 9:2001517.
Science Foundation of China (82100664, 52075285),
the Key-Area Research and Development Program of https://doi.org/10.1002/adhm.202001517
Guangdong Province (2020B090923003), the National 4. Gough A, Soto-Gutierrez A, Vernetti L, et al., 2021, Human
Key Research and Development Program of China Biomimetic Liver Microphysiology Systems in Drug
(2018YFA0703004), Tsinghua University-Peking Union Development and Precision Medicine. Nat Rev Gastroenterol
Medical College Hospital Initiative Scientific Research Hepatol, 18:252–68.
Program (20191080843) Tsinghua University Spring https://doi.org/10.1038/s41575-020-00386-1
Breeze Fund (20201080760), the Natural Science 5. Hiller T, Berg J, Elomaa L, et al., 2018, Generation of a 3D
Foundation of Jiangsu Province (BK20190114), Jiangsu
Province Postdoctoral Research Funding Program Liver Model Comprising Human Extracellular Matrix in an
(2021K116B), Key Project supported by Medical Science Alginate/Gelatin-Based Bioink by Extrusion Bioprinting
and technology development Foundation, Nanjing for Infection and Transduction Studies. Int J Mol Sci,

186 International Journal of Bioprinting (2022)–Volume 8, Issue 3