Learning about liver regeneration from liver-on-a-chip

Organ on a chip, or in the context of liver, liver-on-a-chip or LoC, are recently in the lookout for being bioengineered tools preserving the in vivo cell features and recapitulating the complexity of liver physiology in a controlled microfluidic environment. In the recent years, LoC have been tailored at several levels including biological input, matrix and mechanobiological cues or additional design features such as patterned cultures, multi-organ chips or sensor integration. Latest research in LoC designs include the integration of mechanobiological cues and recapitulation of the most common liver disease etiologies (alcohol associated liver disease, MAFLD or viral infection), enhancing LoC value for hepatotoxicity testing, drug discovery and research. Liver regeneration is a common physiological response to diverse injuries to the liver. In this review, we summarize the latest findings learned from LoC to understand liver regeneration, focusing on the role of transcription growth factor beta (TGFβ), hepatocyte growth factor (HGF) and hypoxia inducible factor 1 alpha (HIF-1α) as key players in the regenerative response by regulating fibrosis, EMT, proliferation and inflammation among others.