Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell-Laden Thermogel: An Effective Tool to Assess Drug-Induced Hepatotoxic Response

Manuele Gori, Sara M. Giannitelli, Miranda Torre, Pamela Mozetic, Franca Abbruzzese, Marcella Trombetta, Enrico Traversa, Lorenzo Moroni, Alberto Rainer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number2001163
Number of pages11
JournalAdvanced Healthcare Materials
Volume9
Issue number21
Early online date17 Sep 2020
DOIs
Publication statusPublished - Nov 2020

Keywords

  • 3D liver models
  • bioprinting
  • drug hepatotoxicity
  • hepatic constructs
  • Pluronic
  • alginate thermogels
  • ACETAMINOPHEN-INDUCED HEPATOTOXICITY
  • IN-VITRO MODEL
  • CYTOCHROME-P450 INDUCTION
  • HEPG2 CELLS
  • LIVER
  • CULTURE
  • TOXICITY
  • HEPATOCYTE
  • PREDICTION
  • MECHANISMS

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