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

Area of Science:

• Biotechnology
• Tissue Engineering
• Regenerative Medicine

Background:

• Epithelial organoids are crucial for tissue engineering but lack scalable, shape-controlled assembly methods.
• Current techniques struggle to create larger, anatomically relevant structures from individual organoids.

Purpose of the Study:

• To present a novel organoid engineering approach for scalable, shape-controlled bio-assembly of epithelial organoids.
• To develop scaffold-free airway tubes with predefined shapes from individual airway organoids.

Main Methods:

• Developed Multi-Organoid Patterning and Fusion (MOrPF) for assembling airway organoids.
• Utilized a matrix-depleted, free-floating environment to promote accelerated fusion of Multi-Organoid Aggregates (MOAs).
• Investigated inter-organoid surface integration, luminal material clearance, and lumen connection in fused organoids.

Main Results:

• MOrPF successfully created upscaled, scaffold-free airway tubes with predefined shapes from individual organoids.
• Fused MOAs exhibited a continuous lumen and maintained prescribed shapes without external scaffolds.
• Theoretical modeling confirmed the shape stability of patterned MOAs based on organoid morphology and fusion forces.
• Fused organoid tubes displayed an unstratified epithelium composed primarily of tracheal basal stem cells.

Conclusions:

• MOrPF provides a robust method for scalable and shape-controlled bio-assembly of epithelial organoids.
• This approach enables the creation of structurally complex organ tubes for integrated organoid devices.
• The technique advances tissue engineering by facilitating the construction of larger, functional organoid structures.