Mechanisms and translational strategies for extrahepatic bile duct regeneration: a review

Extrahepatic bile duct (EHBD) injury remains a major challenge in hepatobiliary medicine, because effective repair requires sustained epithelial integrity, structural continuity, and luminal patency. In this narrative review, we examine the biological basis of EHBD regeneration, focusing on cholangiocytes, peribiliary glands and the surrounding stromal microenvironment. We highlight redox regulation and tissue mechanics, along with signaling pathways that influence epithelial proliferation and fibrotic remodeling. We also compare regenerative strategies by intended application, including cell-based approaches for epithelial restoration, scaffolds for structural reconstruction, and pharmacological interventions to modify injury and repair. However, current evidence remains predominantly experimental, with limited clinical validation. Future translation will require functional epithelial recovery and sustained patency beyond scaffold degradation or withdrawal of temporary support, together with reproducible manufacturing and safety assessment.