Recent advances in hepatic tissue engineering for the treatment of liver disease

Liver failure and chronic liver disease represent escalating global health burdens, exacerbated by donor organ shortages and the limitations of current transplant-based options. Although the liver possesses intrinsic regenerative capacity, chronic inflammation, fibrosis, and architectural disruption can inhibit complete repair, necessitating alternative therapeutic strategies. Hepatic tissue engineering has emerged as a multidisciplinary approach to reconstruct functional liver tissue by integrating stem cell biology, biomaterial science, and advanced bioprinting technologies. This review synthesizes recent advances in stem cell-derived regeneration, focusing on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and liver stem/progenitor cells (LSPCs). MSCs primarily exert immunomodulatory and paracrine effects that remodel fibrotic microenvironments, whereas iPSCs offer scalable, patient-specific hepatocyte-like cells with evolving strategies to improve maturation and safety. LSPCs demonstrate strong lineage commitment and engraftment potential but remain constrained by limited availability and expansion challenges. Complementing cellular approaches, scaffold technologies include decellularized extracellular matrices, synthetic polymers, and emerging biomaterials such as plant-derived, silk-based, and nanostructured systems, providing critical structural, biochemical, and mechanical cues for hepatic organization and vascular integration. In parallel, emerging strategies utilizing ectopic transplantation sites, particularly lymph nodes, highlight the importance of vascularized, immunologically permissive niches for hepatocyte engraftment and expansion, offering a solution to early graft failure caused by insufficient perfusion. Advanced platforms including 3D bioprinting, organoids, and liver-on-a-chip systems enable precise spatial patterning, multicellular coordination, and dynamic microenvironmental control, enhancing metabolic functionality and disease-modeling capacity. Despite these advances, barriers including inadequate vascularization, immune incompatibility, incomplete cellular maturation, and lack of manufacturing standardization continue to limit clinical translation. Integrative strategies combining complementary stem cell populations, bioactive scaffolds, programmable biofabrication technologies, and biologically derived expansion niches represent the most promising pathway toward clinically viable liver reconstruction.