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research article

Bioengineered Tubular Biliary Organoids

Elci, Bilge Sen  
•
Nikolaev, Mikhail  
•
Rezakhani, Saba  
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January 14, 2024
Advanced Healthcare Materials

Liver organoids have emerged as promising in vitro models for toxicology, drug discovery, and disease modeling. However, conventional 3D epithelial organoid culture systems suffer from significant drawbacks, including limited culture duration, a nonphysiological 3D cystic anatomy with an inaccessible apical surface, and lack of in vivo-like cellular organization. To address these limitations, herein a hydrogel-based organoid-on-a-chip model for the development functional tubular biliary organoids is reported. The resulting constructs demonstrate long-term stability for a minimum duration of 45 d, while retaining their biliary organoid identity and exhibiting key cholangiocyte characteristics including transport activities, formation of primary cilia, and protective glycocalyx. Additionally, tubular organoids are susceptible to physical and chemical injury, which cannot be applied in such resolution to classical organoids. To enhance tissue-level complexity, in vitro formation of a perfusable branching network is induced using a predetermined geometry that faithfully mimics the intricate structure of the intrahepatic biliary tree. Finally, cellular complexity is augmented through co-culturing with vascular endothelial cells and fibroblasts. The models described in this study offer valuable opportunities for investigating biliary morphogenesis and elucidating associated pathophysiological mechanisms.|This study explores the intersection of Organ-on-a-Chip technology and liver ductal organoids, leading to the creation of advanced, long-lived tubular organoids with apical accessibility. The models presented here facilitate functional assays, injury modeling, and the faithful reproduction of intricate biliary tissue formation beyond the capabilities of classical 3D organoids.image

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Type
research article
DOI
10.1002/adhm.202302912
Web of Science ID

WOS:001142302900001

Author(s)
Elci, Bilge Sen  
Nikolaev, Mikhail  
Rezakhani, Saba  
Lutolf, Matthias P  
Date Issued

2024-01-14

Publisher

Wiley

Published in
Advanced Healthcare Materials
Subjects

Technology

•

Bile Duct

•

Bioengineering

•

Liver Ductal Organoids

•

Organ-On-A-Chip

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPLUT  
FunderGrant Number

European Union's Horizon 2020 research and innovation programme

EPFL facilities, Bioimaging optics platform (BIOP)

Center of Micronanotechnolgy (CMi)

812954

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Available on Infoscience
February 21, 2024
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/205046
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