A 3D Hepatocyte Model with Composite Nanofibers that Reproduced Human in vivo Drug Clearance Profiles

Abstract

This study presents a novel in vitro 3D hepatocyte model that contains a nanofibrous scaffold designed to mimic the extracellular matrix (ECM) of the human liver, both structurally and biochemically. A modular 3D-printed device housing the ECM scaffold was also developed, readily fitting in well plates. HepaRG hepatocytes cultured on the scaffold exhibited enhanced metabolic activity compared to traditional 2D cultures, indicating improved hepatocyte functionality. Drug clearance studies with lidocaine, clozapine, and fluoxetine demonstrated significantly faster clearance rates on the scaffold, closely aligning with in vivo results from literature, while 2D cultures showed limited metabolic capacity. This model offers a physiologically relevant platform for hepatocyte studies. The findings underscore the model’s potential to advance preclinical drug development by replicating liver-specific functions in vitro.