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Review
. 2025 Sep;53(9):1993-2028.
doi: 10.1007/s10439-025-03779-y. Epub 2025 Jun 28.

Lessons Learned from Liver-on-Chip Platform

Affiliations
Review

Lessons Learned from Liver-on-Chip Platform

Zahra Sadat Razavi et al. Ann Biomed Eng. 2025 Sep.

Abstract

The liver is one of the most studied human organs due to its central role in the metabolism of xenobiotics and pharmaceuticals. In vitro liver models that can mimic liver activities for the goal of studying pathophysiological hints in high-throughput and repeatable conditions have received a lot of attention during the past few decades. Two-dimensional (2D) models have been widely used in the process of screening potentially dangerous substances; nevertheless, these models have been unable to accurately depict the hepatic milieu's three-dimensionality (3D). To get around these limitations, scientists have developed better strategies for three-dimensional culturing that mimic the liver's natural milieu. The major goal of these models is to replicate the structure of the liver. They think about the interplay between parenchymal and nonparenchymal cells and the cellular environment. Newer models of the liver, called livers on a chip (LioCs), have been developed with the intention of simulating physiological fluid flow and, hence, performing key hepatic activities. This was done to ensure normal fluid dynamics. Due to their unrivaled capacity to recapture crucial aspects of the cellular microenvironment of the liver, LioC have been widely utilized in pathophysiology modeling. LioCs are now being used in tissue engineering and drug screening, where they have proven to be an effective tool. From 2D hepatocyte models, which are commonly used for liver toxicity screening, to more recent 3D and LioCs culture strategies, which have been adopted to mimic a more physiological microenvironment in order to study liver diseases, we discuss the development of experimental liver models in this article.

Keywords: In vitro model; Liver metabolism; Liver-on-Chip; Organ-on-a-Chip.

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Conflict of interest statement

Declarations. Conflict of interest: No potential conflict of interest was reported by the authors.

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