The Advanced Integrated Respiratory (AIR) Model: Integration of Air-Liquid Interface Cell Cultures within a Human...

Area of Science:

• Respiratory research
• Toxicology
• Aerosol science

Background:

• Traditional 2D cell cultures lack physiological relevance for studying inhaled substances.
• Accurate assessment of aerosol deposition and toxicity in the respiratory tract is crucial.

Purpose of the Study:

• To introduce the Advanced Integrated Respiratory (AIR) model, a physiologically relevant benchtop system.
• To assess aerosol deposition and interactions within the human respiratory tract.
• To investigate the toxicity of aerosolized Ricinus communis agglutinin-1 (RCA I) using the AIR model.

Main Methods:

• Integration of a 3D human airway cast, vacuum-driven aerosol inhalation, and an air-liquid interface (ALI) cell culture platform.
• Characterization of aerosolized RCA I (particle size, charge, rheology, aerosol performance).
• Real-time quantification using Micro Analytical Device (MAD) and assessment of cytotoxicity and barrier function in human epithelial cells.

Main Results:

• Significant differences in toxic dose thresholds were observed between the AIR model and 2D models.
• RCA I showed significantly increased mass transport across the epithelial cell layer at toxic concentrations.

Conclusions:

• The AIR model represents a significant advancement for studying inhaled aerosol deposition, toxicity, and pharmacokinetics.
• This integrated approach offers a robust tool for predicting lung injury.
• The model enhances the detection capabilities for various inhaled aerosols, including toxins.