Background: Liver diseases are a major global cause of mortality and are in urgent need of innovative therapeutic strategies. This review explores the role of small molecules as key modulators in liver tissue regeneration.
Methods: A comprehensive review of the literature was conducted to evaluate the regenerative potential of small molecules and their underlying mechanisms in liver tissue engineering and regenerative medicine. Particular attention was given to molecules involved in regulating key signaling pathways associated with hepatocyte proliferation, fibrosis inhibition, differentiation, and cell survival.
Results: The findings indicated that compounds such as CHIR99021 (activator of the Wnt/β-catenin signaling pathway), SB431542 (inhibitor of the TGF-β pathway), dexamethasone (inducer of hepatocytic differentiation), and Y-27632 (enhancer of cell survival) can effectively promote hepatocyte proliferation, reduce fibrotic progression, and enhance hepatic functionality through distinct molecular mechanisms. The targeted application of these molecules—especially within engineered microenvironments such as 3D-bioprinted scaffolds or hydrogels—can further improve regenerative outcomes by mimicking native extracellular matrix conditions and supporting cell–matrix interactions.
Conclusion: Despite existing challenges such as safety concerns, the need for targeted delivery systems, and limited clinical evidence, integrating these agents with advanced technologies, including 3D bioprinting and personalized medicine, offers a promising outlook for the treatment of liver diseases. Future efforts should focus on optimizing combinatorial small-molecule therapies, developing smarter delivery platforms, and validating these approaches in clinically relevant models to accelerate translation into regenerative hepatology.