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Bioassembling Macro-Scale, Lumenized Airway Tubes via Multi-Organoid Patterning and Fusion

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Liu, Ye 
Dabrowska, Catherine 
Lee, Joo Hyeon 

Abstract

Epithelial, stem-cell derived organoids are ideal building blocks for tissue engineering, however, scalable and shape-controlled bio-assembly of epithelial organoids into larger and anatomical structures is yet to be achieved. Here, a robust organoid engineering approach, Multi-Organoid Patterning and Fusion (MOrPF), is presented to assemble individual airway organoids of different sizes into upscaled, scaffold-free airway tubes with predefined shapes. Multi-Organoid Aggregates (MOAs) undergo accelerated fusion in a matrix-depleted, free-floating environment, possess a continuous lumen, and maintain prescribed shapes without an exogenous scaffold interface. MOAs in the floating culture exhibit a well-defined three-stage process of inter-organoid surface integration, luminal material clearance, and lumina connection. The observed shape stability of patterned MOAs is confirmed by theoretical modelling based on organoid morphology and the physical forces involved in organoid fusion. Immunofluorescent characterization shows that fused MOA tubes possess an unstratified epithelium consisting mainly of tracheal basal stem cells. By generating large, shape-controllable organ tubes, MOrPF enables upscaled organoid engineering towards integrated organoid devices and structurally complex organ tubes.

Description

Keywords

Stem cells - general, Organ-on-a-chip / lab-on-a-chip / organoids and ex vivo models

Journal Title

TISSUE ENGINEERING PART A

Conference Name

Journal ISSN

1937-3341
1937-335X

Volume Title

Publisher

Wiley Open Access

Rights

All rights reserved
Sponsorship
European Research Council (758865)
European Research Council (ERC-StG 758865; ERC StG 679411, ERC-AdG 786659) Royal Society (107633/Z/15/Z)