High-throughput Bronchus-on-a-Chip system for modeling the human bronchus

Area of Science:

• Biomedical Engineering
• Respiratory Medicine
• Cell Biology

Background:

• Chronic airway inflammation, seen in COPD and asthma, involves goblet cell hyperplasia and metaplasia, leading to airflow obstruction.
• Current in vitro models using horizontal cell cultures do not accurately replicate the human airway's tubular structure or airway stenosis.
• A need exists for advanced in vitro systems that better model human airway physiology for studying chronic inflammatory responses.

Purpose of the Study:

• To develop and validate a novel Bronchus-on-a-Chip (BoC) system for studying chronic airway inflammation.
• To create a more physiologically relevant in vitro model that replicates the human bronchial epithelium's tubular structure and cellular responses.
• To establish a high-throughput platform for assessing mucus hyperproduction and other chronic epithelial responses.

Main Methods:

• A microfluidic Bronchus-on-a-Chip (BoC) system was designed, allowing for the culture of 62 chips in a standard plate.
• Human bronchial epithelial cells were cultured on a collagen extracellular matrix within a tubular structure for up to 35 days.
• The system was characterized using barrier integrity assays, microscopy, histological examination, and exposure to inducers of goblet cell hyperplasia and metaplasia.

Main Results:

• The BoC system successfully cultured human bronchial epithelial cells in a tubular, air-lifted configuration, mimicking native airway structure.
• Epithelial cells differentiated into basal, ciliated, and secretory cell types, consistent with human bronchial epithelium.
• Exposure to inflammatory inducers resulted in mucus hyperproduction, accurately replicating chronic epithelial responses observed in diseases.

Conclusions:

• The developed Bronchus-on-a-Chip system provides a more human-relevant and accurate in vitro model for studying bronchial inflammation.
• This system enhances the assessment of chronic cell responses, including mucus hyperproduction, relevant to COPD and asthma.
• The BoC offers a high-throughput platform for advancing research into airway diseases and potential therapeutic interventions.