Bionic breathing-type airway exposure system for inhalation exposure studies

Abstract We developed an advanced bionic breathing-type airway exposure platform to address the anatomical and physiological limitations of conventional inhalation toxicology models. This system integrates four key technological innovations: a biomimetic respiratory structure with a 3D-bioprinted, anatomically realistic tracheobronchial tree that includes integrated oral/nasal conduits and compliance modules, enabling spatially resolved simulation of aerosol deposition; an intelligent multi-mode breathing control system that reproduces clinical and tobacco-related inhalation patterns at a 0.1-second resolution via triple-route switching; programmable CO₂control to simulate both normal and pathological respiratory gas exchange; and modular sub-regional exposure interfaces for compartment-specific toxicological analysis. Validation studies demonstrated that the platform accurately replicates smoking-related aerosol deposition patterns and detects dose-dependent cytotoxic and pro-inflammatory responses in air-liquid interface cultured human bronchial epithelia. By offering a physiologically realistic model for investigating inhalation toxicity mechanisms and particle dynamics, this platform effectively bridges the gap between in vitro systems and human respiratory responses.