Liver toxicity is a major cause of drug discovery failure in clinical trials and of adverse events leading to regulatory action on approved drugs. It is therefore critical to use in vitro models that are predictive of in vivo liver toxicity in the drug discovery cascade. Current in vitro models often culture immortalised cell lines or primary hepatocytes in 2D tissue culture plates, which results in a decrease in liver-specific functionality, gene expression and longevity. In order to recreate the complex cellular microenvironment of the liver and improve performance and culture longevity of hepatocytes, three-dimensional culture systems are being developed. These are designed to provide more realistic data in drug discovery testing that is predictive of behaviour in the clinic.

The Mimetix® scaffold consists of highly uniform electrospun PLLA microfibres which support the three-dimensional growth of cells. This study investigates the Mimetix scaffold in a 96-well plate format as a culture system for upcyte® Hepatocytes, HepG2 cells and primary human hepatocytes. We assessed cell viability and liver-specific cell functions, such as urea production, albumin synthesis and glucose metabolism in our 3D Mimetix® scaffold vs. 2D culture, as well as CYP activities and acute toxicity of terfenadine. The 3D growth environment provided by the Mimetix scaffold improved cell functionality and CYP activities of the different types of hepatocytes and reduced sensitivity of HepG2 cells to the cytotoxic drug terfenadine.