Materials for liver-on-a-chip: modules, properties, and future directions

The liver is the primary hub of our body for metabolism, detoxification, and drug biotransformation. While conventional two-dimensional cell culture and animal models can only partly recapitulate the complex hepatic microenvironment for the study of the liver, Liver-on-a-chip (LiOC) systems can simulate livers by integrating microfluidics, cell biology and engineered microenvironments. It is crucial to apply materials with specific properties in appropriate places because no single material can meet all the requirements for fabrication of LiOC systems. Moreover, improper material selection may lead to abnormal cell phenotypes and generate false experimental data. By advancing the philosophy of "right material in right place", in this review we systematically evaluated the structure of LiOC modules, including microfluidic, biological and sensing modules, followed by dissection of material-induced artifacts. We then discussed critical challenges including long-term material degradation, batch-to-batch variability, and the gap between laboratory prototypes and industrial production. We also summarize application-oriented material selection criteria and reporting needs for drug screening, hepatotoxicity testing, disease modeling, and personalized medicine. Finally, it outlined future perspectives on possible applications of smart biomimetic materials in LiOC systems, such as stimulus-responsive hydrogels, wood, and piezoelectric hydrogels, along with functionally integrated materials and AI-assisted material screening. This review may provide a framework for material selection and design toward standardized, high-fidelity LiOC platforms.