Modelling cigarette smoke-induced lung vascular dysfunction using an alveolus-on-chip

Area of Science:

• Biomedical Engineering
• Pulmonary Research
• Organ-on-Chip Technology

Background:

• Alveolar damage is key in lung diseases like COPD.
• Understanding alveolar microvascular and epithelial-endothelial interactions is crucial for disease modeling.
• Current models lack the complexity of in vivo alveolar microenvironments.

Purpose of the Study:

• To develop an advanced alveolus-on-chip platform for studying lung physiology and disease.
• To investigate vascular-epithelial crosstalk and responses to environmental insults.
• To create a human-relevant model for lung injury and drug testing.

Main Methods:

• Constructed an open-top, membrane-free alveolus-on-chip with 3D vascular networks using primary human lung endothelial cells and pericytes, co-cultured with alveolar epithelial type 2 (AEC2) cells.
• Utilized continuous flow for vascular network development and assessed stability.
• Exposed the model to whole cigarette smoke (WCS) to evaluate its impact on vascular-epithelial integrity.

Main Results:

• Developed stable, perfusable 3D vascular networks within 6 days.
• Pericytes enhanced capillary-like vessel formation and specific gene expression (EDNRB1).
• AEC2 exposure to WCS caused vascular network disintegration, highlighting a critical interaction.

Conclusions:

• The alveolus-on-chip platform provides a human-relevant system for studying vascular-epithelial crosstalk in the lung.
• This model is valuable for investigating smoke-induced lung injury and immune responses.
• The platform offers potential for future lung disease modeling and therapeutic development.