Three-dimensional reconstruction of a biliary system in a bioengineered liver using decellularized scaffold

Area of Science:

• Regenerative Medicine
• Tissue Engineering
• Hepatology

Background:

• Bioengineered livers offer a promising alternative for liver transplantation in end-stage liver disease.
• Current challenges include reconstructing an integrated biliary system within these engineered organs.

Purpose of the Study:

• To structurally reconstruct a three-dimensional biliary architecture in bioengineered livers.
• To assess bile acid distribution in relation to the reconstructed hepatobiliary architecture.

Main Methods:

• Decellularized rat liver scaffolds were recellularized with primary hepatocytes (PHs) and intrahepatic cholangiocyte organoids (ICOs).
• A perfusion culture system was used for co-culture and assessment of biliary drainage.
• Histological, immunofluorescence, and ELISA analyses were performed.

Main Results:

• Successful engraftment of ICOs into bile ducts and PHs into the parenchymal space was confirmed.
• Reconstructed bile canaliculi and structures resembling native liver architecture were observed.
• Bile acid concentrations in biliary drainage fluid were higher in samples with reconstructed biliary systems.

Conclusions:

• This study demonstrates the successful structural reconstruction of a three-dimensional biliary system in bioengineered livers.
• These findings represent a significant step toward clinical applications of bioengineered livers using decellularization and recellularization techniques.