Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell-Laden Thermogel: An Effective Tool to Assess Drug-Induced Hepatotoxic Response
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- 3D liver models, Pluronic/alginate thermogels, bioprinting, drug hepatotoxicity, hepatic constructs,
- MeSH
- Printing, Three-Dimensional MeSH
- Bioprinting * MeSH
- Hydrogels MeSH
- Chemical and Drug Induced Liver Injury * MeSH
- Tissue Engineering MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hydrogels MeSH
A thermoresponsive Pluronic/alginate semisynthetic hydrogel is used to bioprint 3D hepatic constructs, with the aim to investigate liver-specific metabolic activity of the 3D constructs compared to traditional 2D adherent cultures. The bioprinting method relies on a bioinert hydrogel and is characterized by high-shape fidelity, mild depositing conditions and easily controllable gelation mechanism. Furthermore, the dissolution of the sacrificial Pluronic templating agent significantly ameliorates the diffusive properties of the printed hydrogel. The present findings demonstrate high viability and liver-specific metabolic activity, as assessed by synthesis of urea, albumin, and expression levels of the detoxifying CYP1A2 enzyme of cells embedded in the 3D hydrogel system. A markedly increased sensitivity to a well-known hepatotoxic drug (acetaminophen) is observed for cells in 3D constructs compared to 2D cultures. Therefore, the 3D model developed herein may represent an in vitro alternative to animal models for investigating drug-induced hepatotoxicity.
Center for Translational Medicine St Anne's University Hospital Studentská 812 6 Brno 62500 Czechia
Institute of Nanotechnology National Research Council via Monteroni Lecce 73100 Italy
See more in PubMed
S. M. Giannitelli, A. Rainer, D. Accoto, S. De Porcellinis, E. M. De-Juan-Pardo, E. Guglielmelli, M. Trombetta, in Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior, (Eds: P. R. Fernandes, P Bartolo), Springer, Dordrecht 2014, pp. 113-128.
S. Li, Y. Yan, Z. Xiong, C. W. R. Zhang, X. Wang, J. Bioact. Compat. Polym. 2009, 24, 84.
C. Chimate, B. Koc, Int. J. Adv. Manuf. Technol. 2014, 75, 317.
S. Sakai, H. Ohi, T. Hotta, H. Kamei, M. Taya, Biopolymers 2018, 109, e23080.
N. E. Fedorovich, J. R. De Wijn, A. J. Verbout, J. Alblas, W. J. A. Dhert, Tissue Eng., Part A 2008, 14, 127.
A. Faulkner-Jones, C. Fyfe, D.-J. Cornelissen, J. Gardner, J. King, A. Courtney, W. Shu, Biofabrication 2015, 7, 044102.
C. Kryou, V. Leva, M. Chatzipetrou, I. Zergioti, Bioengineering 2019, 6, 95.
Y. Zhao, R. Yao, L. Ouyang, H. Ding, T. Zhang, K. Zhang, S. Cheng, W. Sun, Biofabrication 2014, 6, 035001.
F. P. W. Melchels, T. J. Klein, J. Malda, P. J. Bartolo, D. W. Hutmacher, Prog. Polym. Sci. 2012, 37, 1079.
A. Khademhosseini, G. Camci-Unal, 3d Bioprinting in Regenerative Engineering: Principles and Applications, CRC Press, Boca Raton, FL 2018.
R. Suntornnond, J. An, C. K. Chua, Int. J. Bioprint. 2017, 3, 83.
T. Billiet, M. Vandenhaute, J. Schelfhout, S. Van Vlierberghe, P. Dubruel, Biomaterials 2012, 33, 6020.
A. Dalmoro, A. A. Barba, G. Lamberti, M. Grassi, M. d'Amore, Adv. Polym. Technol. 2012, 31, 219.
S. Das, F. Pati, S. Chameettachal, S. Pahwa, A. R. Ray, S. Dhara, S. Ghosh, Biomacromolecules 2013, 14, 311.
T. Zhang, Y. Yan, X. Wang, Z. Xiong, F. Lin, R. Wu, R. Zhang, J. Bioact. Compat. Polym. 2007, 22, 19.
P. Mozetic, S. M. Giannitelli, M. Gori, M. Trombetta, A. Rainer, J. Biomed. Mater. Res., Part A 2017, 105, 2582.
V. Chiono, S. Sartori, M. Boffito, E. Gioffredi, M. Trombetta, P. Mozetic, A. Rainer, S. M. Giannitelli, WO2016194011 A1, 2016.
I. Ozbolat, M. Hospodiuk, Biomaterials 2016, 76, 321.
N. E. Fedorovich, W. Schuurman, H. M. Wijnberg, H.-J. Prins, P. R. van Weeren, J. Malda, J. Alblas, W. J. A. Dhert, Tissue Eng., Part C 2012, 18, 33.
E. Goulart, L. C. de Caires-Junior, K. A. Telles-Silva, B. H. S. Araujo, S. A. Rocco, M. Sforca, I. L. de Sousa, G. S. Kobayashi, C. M. Musso, A. F. Assoni, D. Oliveira, E. Caldini, S. Raia, P. I. Lelkes, M. Zatz, Biofabrication 2019, 12, 015010.
A. Skardal, M. Devarasetty, C. Rodman, A. Atala, S. Soker, Ann. Biomed. Eng. 2015, 43, 2361.
J. Wong, S. Shi, H. Wang, F. Xing, Y. Quan, M. Zhao, BioRxiv 2019, 499723.
P. Pingitore, K. Sasidharan, M. Ekstrand, S. Prill, D. Lindén, S. Romeo, Int. J. Mol. Sci. 2019, 20, 1629.
N. S. Bhise, V. Manoharan, S. Massa, A. Tamayol, M. Ghaderi, M. Miscuglio, Q. Lang, Y. Shrike Zhang, S. R. Shin, G. Calzone, N. Annabi, T. D. Shupe, C. E. Bishop, A. Atala, M. R. Dokmeci, A. Khademhosseini, Biofabrication 2016, 8, 014101.
X. Ma, X. Qu, W. Zhu, Y. Li, S. Yuan, H. Zhang, J. Liu, P. Wang, C. Lai, F. Zanella, G.-S. Feng, F. Sheikh, S. Chien, S. Chen, Proc. Natl. Acad. Sci. 2016, 113, 2206.
D. G. Nguyen, J. Funk, J. B. Robbins, C. Crogan-Grundy, S. C. Presnell, T. Singer, A. B. Roth, PLoS One 2016, 11, e0158674.
L. M. Norona, D. G. Nguyen, D. A. Gerber, S. C. Presnell, E. L. LeCluyse, Toxicol. Sci. 2016, 154, 354.
X. Ma, J. Liu, W. Zhu, M. Tang, N. Lawrence, C. Yu, M. Gou, S. Chen, Adv. Drug Delivery Rev. 2018, 132, 235.
A. Mazzocchi, M. Devarasetty, R. Huntwork, S. Soker, A. Skardal, Biofabrication 2018, 11, 015003.
T. Hiller, J. Berg, L. Elomaa, V. Röhrs, I. Ullah, K. Schaar, A.-C. Dietrich, M. Al-Zeer, A. Kurtz, A. Hocke, S. Hippenstiel, H. Fechner, M. Weinhart, J. Kurreck, Int. J. Mol. Sci. 2018, 19, 3129.
D. Choudhury, H. W. Tun, T. Wang, M. W. Naing, Trends Biotechnol. 2018, 36, 787.
M. Schutte, B. Fox, M.-O. Baradez, A. Devonshire, J. Minguez, M. Bokhari, S. Przyborski, D. Marshall, Assay Drug Dev. Technol. 2011, 9, 475.
S. S. Bale, L. Moore, M. Yarmush, R. Jindal, Tissue Eng., Part B 2016, 22, 383.
S. M. Giannitelli, P. Mozetic, M. Trombetta, A. Rainer, in Additive Manufacturing: Innovations, Advances, and Applications, (Eds: T. S. Srivatsan, T. S. Sudarshan) CRC Press, Boca Raton, FL 2015, Ch. 6.
I. R. Schmolka, J. Am. Oil Chem. Soc. 1977, 54, 110.
M. Müller, J. Becher, M. Schnabelrauch, M. Zenobi-Wong, Biofabrication 2015, 7, 035006.
M. Kang, C. A. Day, A. K. Kenworthy, E. DiBenedetto, Traffic 2012, 13, 1589.
V. Chiono, P. Mozetic, M. Boffito, S. Sartori, E. Gioffredi, A. Silvestri, A. Rainer, S. M. Giannitelli, M. Trombetta, D. Nurzynska, F. Di Meglio, C. Castaldo, R. Miraglia, S. Montagnani, G. Ciardelli, Interface Focus 2014, 4, 20130045.
A. Rainer, S. M. Giannitelli, D. Accoto, S. De Porcellinis, E. Guglielmelli, M. Trombetta, Ann. Biomed. Eng. 2012, 40, 966.
R. Seyedmahmoud, P. Mozetic, A. Rainer, S. M. Giannitelli, F. Basoli, M. Trombetta, E. Traversa, S. Licoccia, A. Rinaldi, J. Biomed. Mater. Res., Part A 2015, 103, 103.
C. Colosi, M. Costantini, R. Latini, S. Ciccarelli, A. Stampella, A. Barbetta, M. Massimi, L. Conti Devirgiliis, M. Dentini, J. Mater. Chem. B 2014, 2, 6779.
M. Esch, J. Prot, Y. Wang, P. Miller, J. Llamas-Vidales, B. A. Naughton, D. R. Applegate, M. L. Shuler, Lab Chip 2015, 15, 2269.
M. Y. Zhang, P. J. Lee, P. J. Hung, T. Johnson, L. P. Lee, M. R. K. Mofrad, Biomed. Microdevices 2008, 10, 117.
J. Vandesompele, K. De Preter, F. Pattyn, B. Poppe, N. Van Roy, A. De Paepe, F. Speleman, Genome Biol. 2002, 3, research0034.1.
H. Weichert, I. Blechschmidt, S. Schröder, H. Ambrosius, Allerg. Immunol. 1991, 37, 139.
V. Lewerenz, S. Hanelt, C. Nastevska, C. El-Bahay, E. Röhrdanz, R. Kahl, Toxicology 2003, 191, 179.
H. Parikh, N. Pandita, A. Khanna, Pharm. Biol. 2015, 53, 975.
S.-F. Lan, B. Starly, Toxicol. Appl. Pharmacol. 2011, 256, 62.
M. R. McGill, H.-M. Yan, A. Ramachandran, G. J. Murray, D. E. Rollins, H. Jaeschke, Hepatology 2011, 53, 974.
S. C. Ramaiahgari, M. W. den Braver, B. Herpers, V. Terpstra, J. N. M. Commandeur, B. van de Water, L. S. Price, Arch. Toxicol. 2014, 88, 1083.
Y.-C. Toh, T. C. Lim, D. Tai, G. Xiao, D. van Noort, H. Yu, Lab Chip 2009, 9, 2026.
R. Kostadinova, F. Boess, D. Applegate, L. Suter, T. Weiser, T. Singer, B. Naughton, A. Roth, Toxicol. Appl. Pharmacol. 2013, 268, 1.
A. Ghallab, EXCLI J. 2014, 13, 1286.
J. M. Choi, S. J. Oh, S. Y. Lee, J. H. Im, J. M. Oh, C. S. Ryu, H. C. Kwak, J.-Y. Lee, K. W. Kang, S. K. Kim, Arch. Pharm. Res. 2015, 38, 691.
X. F. Koe, T. S. Tengku Muhammad, A. S.-C. Chong, H. A. Wahab, M. L. Tan, Food Sci. Nutr. 2014, 2, 500.
Y. Zhengyin, G. W. Caldwell, Curr. Top. Med. Chem. 2001, 1, 403.
S. Cho, A. Tripathi, G. Chlipala, S. Green, H. Lee, E. B. Chang, H. Jeong, PLoS One 2017, 12, e0182977.
H. Yoshioka, T. Nonogaki, H. Ohnishi, N. Fukuishi, M. Yoshikawa, M.-Y. Gui, Y.-R. Jin, X.-W. Li, Y. Adachi, N. Ohno, K. Takeya, Y. Hitotsuyanagi, N. Miura, Y. Aoyagi, Biomed. Res. 2018, 39, 251.
S. Wilkening, F. Stahl, A. Bader, R. A. Prough, Drug Metab. Dispos. 2003, 31, 1035.
K. L. Schmeichel, M. J. Bissell, J. Cell Sci. 2003, 116, 2377.
T. Sun, S. Jackson, J. W. Haycock, S. MacNeil, J. Biotechnol. 2006, 122, 372.
V. Y. Soldatow, E. L. LeCluyse, L. G. Griffith, I. Rusyn, Toxicol. Res. 2013, 2, 23.
T. Grix, A. Ruppelt, A. Thomas, A.-K. Amler, B. Noichl, R. Lauster, L. Kloke, Genes 2018, 9, 176.
A. Asthana, W. S. Kisaalita, Drug Discovery Today 2012, 17, 810.
F. Hirschhaeuser, H. Menne, C. Dittfeld, J. West, W. Mueller-Klieser, L. A. Kunz-Schughart, J. Biotechnol. 2010, 148, 3.
A. M. Larson, J. Polson, R. J. Fontana, T. J. Davern, E. Lalani, L. S. Hynan, J. S. Reisch, F. V. Schiødt, G. Ostapowicz, A. O. Shakil, W. M. Lee, Hepatology 2005, 42, 1364.
J. G. M. Bessems, N. P. E. Vermeulen, Crit. Rev. Toxicol. 2001, 31, 55.
H. Jaeschke, M. L. Bajt, Toxicol. Sci. 2006, 89, 31.
S. R. Khetani, S. N. Bhatia, Nat. Biotechnol. 2008, 26, 120.
E. L. LeCluyse, R. P. Witek, M. E. Andersen, M. J. Powers, Crit. Rev. Toxicol. 2012, 42, 501.
S. A. Langhans, Front. Pharmacol. 2018, 9, 6.
S. R. Caliari, J. A. Burdick, Nat. Methods 2016, 13, 405.
Y. S. Zinchenko, L. W. Schrum, M. Clemens, R. N. Coger, Tissue Eng. 2006, 12, 751.
V. L. Tsang, A. A. Chen, L. M. Cho, K. D. Jadin, R. L. Sah, S. DeLong, J. L. West, S. N. Bhatia, FASEB J. 2007, 21, 790.
M. Yamada, A. Hori, S. Sugaya, Y. Yajima, R. Utoh, M. Yamato, M. Seki, Lab Chip 2015, 15, 3941.
M. Gori, B. Barbaro, M. Arciello, R. Maggio, C. Viscomi, A. Longo, C. Balsano, J. Cell. Physiol. 2014, 229, 1182.
N. B. Javitt, FASEB J. 1990, 4, 161.
K. Bhadriraju, C. S. Chen, Drug Discovery Today 2002, 7, 612.
