Development of an acute inhalation toxicity testing method based on a lung-on-a-chip

Area of Science:

• Toxicology
• Biotechnology
• Microfluidics

Background:

• No standardized in vitro methods for acute inhalation toxicity exist.
• Mimicking the human lung's physiological environment in vitro is challenging.
• Microfluidic lung-on-a-chip (LOC) models offer potential for simulating lung function.

Purpose of the Study:

• To establish optimal conditions for an LOC model for acute inhalation toxicity testing.
• To evaluate the predictive capacity of the LOC system for chemical toxicity.

Main Methods:

• Calu-3 and MRC-5 cells were cultured in a microfluidic chip under air-liquid interface (ALI) conditions.
• Epithelial barrier integrity was assessed via trans-epithelial electrical resistance and permeability.
• Acute inhalation toxicity was predicted using cell viability assays on reference chemicals.

Main Results:

• Optimal epithelial barrier integrity was achieved on day 7 with 2.5% mechanical stretching.
• The LOC model demonstrated 78% sensitivity, 67% specificity, and 72% accuracy in toxicity prediction.
• Receiver operating characteristic (ROC) curve analysis confirmed the model's predictive capacity.

Conclusions:

• The optimized LOC system shows potential as a standardized in vitro method for acute inhalation toxicity testing.
• This microfluidic technology integrated with human-relevant cells offers a practical and ethical alternative to animal testing.
• Further validation is warranted for this promising in vitro toxicology approach.