Bioengineered Bile Duct for Liver Regenerative Medicine and Bile Duct Reconstruction

Abstract

Bioengineered tubular bile ducts are an emerging strategy in liver regenerative medicine and extrahepatic bile duct reconstruction, offering potential solutions to address biliary diseases and improve outcomes in liver transplantation. Disorders of the biliary system, such as biliary atresia, primary sclerosing cholangitis, and bile duct injury, often result in irreversible damage and cannot be adequately treated with conventional therapies. This review explores the latest advancements in the bioengineering of both intrahepatic and extrahepatic bile ducts, focusing on approaches that leverage cholangiocyte biology, stem cell technologies, and biomaterial innovations. Key cell sources, including primary cholangiocytes, induced pluripotent stem cells (iPSCs), liver progenitor cells (LPCs), and transdifferentiated hepatocytes, are discussed for their potential to generate functional bile duct epithelial cells capable of restoring biliary function. The role of biomaterials in providing structural support and promoting cellular growth and differentiation is critically examined, emphasizing synthetic and natural scaffolds, such as poly(lactic acid) (PLA) and collagen-based materials, for creating viable tubular structures. This review provides a comprehensive overview of the current progress and challenges in bioengineered bile duct tissue, focusing on the goals of enhancing liver regeneration and enabling extrahepatic bile duct reconstruction for clinical applications. Integrating cellular, biomaterial, and bioengineered strategies offers promising avenues for advancing treatments for biliary diseases and improving liver transplantation outcomes.

Keywords: bioartificial; bioengineered bile duct; biomaterials; cholangiopathies; liver regeneration.

FIGURE 1

Cholangiocyte organoids could be generated from patients' tissue‐derived cell sources, including primary cholangiocytes, mature hepatocyte‐derived chemically indued progenitor cells and isolated progenitor cells.