Bioprinted Ventilated 3D Alveoliform Epithelial Sacculoids.

Area of Science:

• Biomedical Engineering
• Respiratory Biology
• Stem Cell Biology

Background:

• Current ex-vivo lung models lack structural hierarchy and mechanical simulation.
• Existing models fail to replicate the complex environment of alveolar sacs.
• There's a need for advanced models to study lung diseases and mechanics.

Purpose of the Study:

• To create a 3D ex-vivo model of human distal lung air sacs.
• To incorporate structural hierarchy and mechanical ventilation into lung organoids.
• To enable studies on epithelial plasticity, viral pathogenesis, and biomechanical signaling.

Main Methods:

• Bioprinting of pluripotent stem cell-derived alveolar epithelial type II cells (ATIIs) into 3D geometries.
• Development of a custom air-driven platform for 3D ventilation of sacculoids.
• Analysis of cellular organization, polarization, surfactant secretion, and signaling pathways.

Main Results:

• Established 3D alveolar epithelial sacculoids (AES) that self-organized into lumenized sacs.
• AES exhibited polarized epithelia, surfactant secretion, and cell heterogeneity.
• Ventilation induced Hippo signaling, driving ATII-to-ATI remodeling and supporting antiviral responses.

Conclusions:

• AES provide a physiologically ventilated model of the human alveolar niche.
• This model facilitates mechanistic studies of epithelial plasticity and viral pathogenesis.
• AES offer a foundation for advanced ex-vivo respiratory research and drug development.