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Bio-assembling Macro-Scale, Lumenized Airway Tubes of Defined Shape via Multi-Organoid Patterning and Fusion.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Liu, Ye 
Dabrowska, Catherine 
Mavousian, Antranik 
Strauss, Bernhard 
Meng, Fanlong 

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

bio‐assembly, organoids, respiratory system, tissue engineering, tissue morphogenesis, Animals, Biomimetics, Cell Fusion, Mice, Models, Animal, Morphogenesis, Organoids, Stem Cells, Tissue Culture Techniques, Tissue Engineering, Trachea

Journal Title

Adv Sci (Weinh)

Conference Name

Journal ISSN

2198-3844
2198-3844

Volume Title

8

Publisher

Wiley
Sponsorship
Wellcome Trust (107633/Z/15/Z)
European Research Council (679411)
European Research Council (758865)
Medical Research Council (MC_PC_17230)