Construction of functional biliary epithelial branched networks with predefined geometry using digital light stereolithography

Cholangiocytes, biliary epithelial cells, are known to spontaneously self-organize into spherical cysts with a central lumen. In this work, we explore a promising biocompatible stereolithographic approach to encapsulate cholangiocytes into geometrically controlled 3D hydrogel structures to guide them towards the formation of branched tubular networks. We demonstrate that within the appropriate mix of hydrogels, normal rat cholangiocytes can proliferate, migrate, and organize into branched tubular structures with walls consisting of a cell monolayer, transport fluorescent dyes into the luminal space, and show markers of epithelial maturation such as primary cilia and continuous tight junctions. The resulting structures have dimensions typically found in the intralobular and intrahepatic biliary tree and are stable for weeks, without any requirement of bulk supporting material, thereby offering total access to the external side of these biliary epithelial constructs.

Automated summary

Cholangiocytes, biliary epithelial cells, are able to self-organize into spherical cysts with a central lumen naturally. This study demonstrates a biocompatible stereolithographic approach to encapsulate cholangiocytes in hydrogel structures, guiding them to form branched tubular networks. The resulting structures, resembling those found in the biliary tree, show stable organization and epithelial maturation markers without the need for additional supporting materials.