Development of Liver-on-Chip Integrating a Hydroscaffold Mimicking the Liver’s Extracellular Matrix

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Messelmani, Taha | Le Goff, Anne | Souguir, Zied | Maes, Victoria | Roudaut, Méryl | Vandenhaute, Elodie | Maubon, Nathalie | Legallais, Cécile | Leclerc, Eric | Jellali, Rachid

Edité par CCSD ; MDPI -

International audience. The 3Rs guidelines recommend replacing animal testing with alternative models. One of thesolutions proposed is organ-on-chip technology in which liver-on-chip is one of the most promisingalternatives for drug screening and toxicological assays. The main challenge is to achieve the relevantin vivo-like functionalities of the liver tissue in an optimized cellular microenvironment. Here, weinvestigated the development of hepatic cells under dynamic conditions inside a 3D hydroscaffoldembedded in a microfluidic device. The hydroscaffold is made of hyaluronic acid and composed ofliver 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 for21 days. After seeding, the cells formed aggregates and proliferated, forming 3D spheroids. The cellviability, functionality, and spheroid integrity were investigated and compared to static cultures. Theresults showed a 3D aggregate organization of the cells up to large spheroid formations, high viabilityand albumin production, and an enhancement of HepG2 cell functionalities. Overall, these resultshighlighted the role of the liver-on-chip model coupled with a hydroscaffold in the enhancementof cell functions and its potential for engineering a relevant liver model for drug screening anddisease study.

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