Advanced 3D In Vitro Liver Fibrosis Models: Spheroids, Organoids, and Liver-on-Chips

Liver fibrosis (LF) is a progressive and increasingly prevalent condition, yet current therapeutic options remain limited. This underscores the growing demand for advanced three-dimensional (3D) preclinical models that better recapitulate the complex pathophysiology of human LF and overcome the limitations of conventional systems. Although a number of in vitro models have been proposed in recent years, many still rely on two-dimensional (2D) hepatocyte cultures, which fail to represent the multicellular interactions and spatial architecture of the fibrotic liver. In contrast, 3D in vitro models, including spheroids, organoids, and liver-on-a-chip (LoC) platforms, offer more physiologically relevant microenvironments, enabling improved disease modeling and patient-specific drug testing. In this review, we summarize current bioengineering strategies for constructing 3D LF models and highlight their advantages, limitations, and future directions for clinical translation.