Development of Liver-on-Chip Integrating a Hydroscaffold Mimicking the Liver’s Extracellular Matrix
Abstract
The 3Rs guidelines recommend replacing animal testing with alternative models. One of the
solutions proposed is organ-on-chip technology in which liver-on-chip is one of the most promising
alternatives for drug screening and toxicological assays. The main challenge is to achieve the relevant
in vivo-like functionalities of the liver tissue in an optimized cellular microenvironment. Here, we
investigated the development of hepatic cells under dynamic conditions inside a 3D hydroscaffold
embedded in a microfluidic device. The hydroscaffold is made of hyaluronic acid and composed of
liver extracellular matrix components (galactosamine, collagen I/IV) with RGDS (Arg-Gly-Asp-Ser)
sites for cell adhesion. The HepG2/C3A cell line was cultured under a flow rate of 10 L/min for
21 days. After seeding, the cells formed aggregates and proliferated, forming 3D spheroids. The cell
viability, functionality, and spheroid integrity were investigated and compared to static cultures. The
results showed a 3D aggregate organization of the cells up to large spheroid formations, high viability
and albumin production, and an enhancement of HepG2 cell functionalities. Overall, these results
highlighted the role of the liver-on-chip model coupled with a hydroscaffold in the enhancement
of cell functions and its potential for engineering a relevant liver model for drug screening and
disease study.
Origin | Publication funded by an institution |
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