3D bioprinting of a cell-laden thermogel: an effective tool to assess drug-induced hepatotoxic response

Introduction The formulation of bioinks with cytocompatible gelation mechanisms and tailored chemo-mechanical behavior represents one of the recent trends in bioprinting [1]. Here, a thermoresponsive Pluronic/alginate semi-synthetic hydrogel was developed for the fabrication of 3D hepatic constructs, with the aim to investigate liver-specific metabolic activity compared to conventional 2D cultures [2]. Experimental methods Pluronic/alginate cell-laden constructs were fabricated in combination with HepG2/C3A cells by pressure-assisted deposition, exploiting the multi-step gelation mechanism of the bioink. The bioprinting method was validated in terms of cell viability and metabolic activity. Hepatotoxicity testing was also performed using acetaminophen (paracetamol, APAP) as a model drug. Results and discussion A novel method for bioprinting hepatic cells was developed, via a robust and reproducible manufacturing process, characterized by high-shape fidelity, mild depositing conditions and easily manageable gelation mechanism. The dissolution of the sacrificial Pluronic templating agent significantly ameliorated the diffusive properties of the printed hydrogel. High cell viability and liver-specific metabolic activity were reported for the 3D constructs. A markedly increased sensitivity to a well-known hepatotoxic drug (acetaminophen) was observed for cells in 3D constructs compared to 2D cultures. Conclusion The developed 3D model may represent an innovative in vitro platform for investigating drug-induced hepatotoxicity.