Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees

Background and Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced disease the only curative approach is transplantation. However, less than 10% of in need get a transplant due to limited organ availability. To circumvent this challenge, there has been great focus generating bioengineered liver. Despite its essential role functions, functional biliary system not yet developed. In framework, exploration epithelial cell self-organogenesis microengineering-driven geometrical confinement allow envision bioengineering biomimetic intrahepatic tract. Approach: three-dimensional (3D) bile ducts were built vitro by restricting adhesion two-dimensional (2D) patterns guide self-organization. Tree shapes mimicking configuration human micropatterned on glass slides, attachment these areas. Different tree geometries culture conditions explored stimulate normal rat cholangiocytes (NRCs) used as model, either alone or co-culture umbilical endothelial cells (HUVECs). Results: Pre-seeding micropatterns HUVECs promoted luminogenesis higher efficiency yield branched tubes. Lumen formation, apico-basal polarity, preservation cholangiocyte phenotype confirmed. Moreover, intact structures detached from further manipulation. Conclusion: This study presents physiologically relevant 3D duct networks 2D micropatterns. opens opportunities investigating organogenesis, physiopathology, drug testing.