Advanced In Vitro Platforms for Experimental Liver Research: From Organoids and Liver‐on‐Chip to Omics and Artificial Intelligence

Hepatocytes perform essential physiological functions in the human body. Gaining more profound insight into the liver structure, diseases, and physiology by using in vitro models can help to propose more relevant clinical applications. Conventional in vitro liver models, such as two-dimensional (2D) cell cultures, fail to adequately replicate the hepatic microenvironment, even when improved by adding additional cell types and extracellular matrix (ECM). These models do not address all necessary key components to mimic in vivo conditions, particularly multicellularity, specific ECM, and proper biophysical and biochemical parameters. Organoids, 3D-bioprinted constructs, and liver-on-chip platforms establish physiologically relevant models by improving cell-cell and cell-matrix interactions and multicellular architecture. For a comprehensive understanding of the liver's interconnections with related tissues and organs, a multi-organ-on-chip is a useful platform for more systemic studies. Also, other interdisciplinary approaches, particularly omics and artificial intelligence (AI), can enhance the accuracy of experimental and pre-clinical data achieved by such advanced in vitro liver platforms. This review highlights developing platforms for integrated approaches in experimental liver studies to enable researchers to have a holistic view of the liver in physiologic and pathologic conditions.