Engineering liver disease models in vitro: emerging trends and innovations

In vitro liver disease modelling, a rapidly evolving field, has become a multidimensional endeavour aimed at more precisely and effectively recapitulating the complexity of hepatic pathophysiology. This review systematically outlines the essential structural and cellular components of the liver as foundational elements for model design. Emphasising pathophysiological states rather than disease hallmarks, we discuss key liver injury paradigms, including hepatic steatosis, drug-induced hepatotoxicity, fibrogenesis, tumourigenesis and cholestatic injury. Each section integrates cellular mechanisms with model development strategies, highlighting advances in co-culture systems, multicellular organoids and liver-on-a-chip platforms. Although challenges persist, emerging platforms are increasingly capable of capturing multicellular crosstalk, structural heterogeneity and injury-response dynamics. Moving forward, model utility will depend not only on structural mimicry but on the ability to produce biologically meaningful outputs under experimentally controlled conditions.