Injectable cell-laden gelatin-chondroitin sulphate hydrogels for liver in vitro models

Liver extracellular matrix-based models that precisely reproduce liver physiology and functions are required as 3D culture microenvironments for multiple applications in toxicology and metabolism, or for understanding the mechanisms implicated in liver disease. We introduced injectable gelatin-chondroitin sulphate (Gel/CS) hydrogels for culturing HepG2 cells, and evaluated the mechanical properties and functionality of cells in different Gel/CS compositions. The Gel/CS hydrogels exhibited soft mechanical properties and allowed the HepG2 culture. The characterisation and comparison of 3D cultures to standard monolayer systems revealed the regulation of key hepatic markers (i.e. CYP3A4, GSTA1) when cells were cultured in the Gel/CS hydrogels compared to 2D cultures, and also enhanced urea and albumin production, which would indicate increased cells functionality. This study underpins 3D in vitro models based on the Gel/CS hydrogels that can be used for different hepatology applications by offering increased predictivity and physiological relevance compared to current in vitro models.