Bioinspired Bioinks for the Fabrication of Chemomechanically Relevant Standalone Disease Models of Hepatic Steatosis

Abstract

Hepatotoxicity‐related issues are poorly predicted during preclinical trials, as their relevance is limited by the inadequacy to screen all the non‐physiological subclasses of the population. These pitfalls could be solved by implementing complex in vitro models of hepatic physiology and pathologies in the preclinical phase. To produce these platforms, we focused on extrusion‐based bioprinting, since it allows to manufacture tridimensional cell‐laden constructs with controlled geometries, in a high‐throughput manner. We propose different bioinks, whose formulation was tailored to mimic the chemomechanical environment of hepatic steatosis, the most prevalent hepatic disorder worldwide. Internally crosslinked alginate hydrogels were chosen as structural components of the inks. Their viscoelastic properties (G’ = 512‐730 Pa and G’’ = 94‐276 Pa, depending on frequency) were tuned to mimic those of steatotic liver tissue. Porcine hepatic ECM was introduced as a relevant biochemical cue. Sodium oleate was added to recall the accumulation of lipids in the tissue. Downstream analyses on 14‐layered bioprinted structures cultured for 10 days revealed the establishment of steatotic‐like features (intracellular lipid vesicles, viability decrease up to ≈50%) without needing external conditionings. The presented bioinks are thus suitable to fabricate complex models of hepatic steatosis to be implemented in a high‐throughput experimental frame.This article is protected by copyright. All rights reserved