Three Dimensional Biomimetic Liver Models to Reconstitute Metabolic Dysfunction-Associated Steatohepatitis (MASH) In Vitro: Hope and Reality.

This review article provides an in-depth exploration of recent advancements in in vitro liver models for studying metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease linked to metabolic disorders. The article highlights the significance of these models in mimicking the liver's complex microarchitecture and physiological functions, offering an essential platform for understanding MASH pathogenesis and testing potential therapeutic agents. Key innovations discussed include biomimetic three-dimensional cultures, microfluidic liver-on-a-chip systems, liver organoids, and scaffold-based approaches. These modals partially recapitulate key features of MASH, such as lipid accumulation, inflammation, and fibrosis, while enabling the investigation of signaling pathways and molecular mechanisms underlying the disease. Additionally, the article examines the advantages and limitations of various models, with a focus on their application in drug discovery, toxicity assessment, and personalized medicine. By facilitating a deeper understanding of MASH's intricate biology, these models hold promise for the identification of new therapeutic targets and the development of more effective treatment strategies for a disease with no current Food and Drug Administration (FDA)-approved pharmacological therapies. This review underscores the transformative potential of bioengineered platforms in MASH research and their role in advancing the future of liver disease management.