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Bioprinting of a Hepatic Tissue Model
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           Figure 5. Liver function-related mRNA and protein expression in the 2D, SW, and 3DP hepatic tissue models. (A) Detection of liver function-
           related mRNA expression by qRT-PCR: cytochrome P450-1A2, cytochrome P450-3A4, α-1-Antitrypsin (AAT), tyrosine aminotransferase
           (TAT), albumin, transferrin, asialoglycoprotein receptor-1, and cytokeratin-18. Data are presented as means ± SD (n = 3). (B) Measurement
           of liver function-related proteins by ELISA: AAT, albumin, and blood urea nitrogen. Data are presented as means ± SD (n = 12). *P < 0.05,
           **P < 0.01, ***P < 0.001.

            A                      B                           Table 1. IC50 values (mM) of APAP-induced hepatotoxic response.
                                                                             2D model    SW model   3DP model
                                                               24 h treatment  11.89       26.48       49.54
                                                               48 h treatment   0.89       16.41       12.88

                                                               does  not  always  meet  the  standard  of  drug  screening
                                                               due to its low reproducibility. Artificial microstructures
            C                                                  in  microfluidic  devices  ensure  the  establishment  of
                                                               controllable microenvironments. However, high cost and
                                                               specific requirements for fabrication technology limit the
                                                               large-scale generation of hepatic tissues. Compared to cell
                                                               microencapsulation and microfluidics, 3D bioprinting has
                                                               unique benefits for the efficient, scalable, and reproducible
                                                               fabrication of hepatic tissue models, which could easily
                                                               meet the demands of high-throughput drug screening and
           Figure  6.  APAP-induced  hepatotoxicity  of  the  hepatic  tissue
           models. (A) Dose-response curves after 24 h treatment of APAP.   toxicological tests.
           (B)  Dose-response  curves  after  48  h  of  treatment  with  APAP.   Given these merits, we chose 3D bioprinting as the
           (C) Expression of cytochrome CYP1A2 measured at the 2 time   tissue model construction method for this study of hiPSCs,
           points under the APAP exposure of IC50 concentrations. Data are   an easily accessible and highly expandable hepatic cell
           presented as means ± SD (n = 3). *P < 0.05, **P < 0.01.  source. A standard type of bioink alginate-gelatin, which
                                                               has  been  widely  used  for  bioprinting  various  types  of
           bioprinting [3,36] . Cell  microencapsulation  is a  relatively   tissue  models [37-39]  including  liver  tissue [12,13,18] ,  was
           easy way to generate liver microtissues, but this method   employed  to construct a simple and practical  hepatic


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