Bionic breathing-type airway exposure system for inhalation exposure studies.

To address limitations in anatomical fidelity and respiratory dynamics of animal-based and static in vitro models, a personalized bionic airway exposure system was developed as a physiologically relevant alternative. The platform integrates an anatomically accurate human airway replica (trachea to G3 bronchi, reconstructed from chest CT and 3D printing), millisecond-synchronized dynamic breathing control with five waveforms and oral/nasal/combined inhalation routes, branch-level deposition analysis, independent oral and nasal circuits, CO2 exchange, and multi-zone exposure interfaces. Using programmable logic control, the system simulates breathing from normal to pathological states, including smoking-integrated patterns, while enabling gas exchange and site-specific exposure testing. Validation demonstrates that the system recapitulates right-dominant airflow distribution (right main bronchus 51.6% ± 0.1% vs. left 48.4% ± 0.1%) and differential particle deposition between inhalation patterns (large-loop 78.0% ± 1.6% vs. small-loop 61.7% ± 1.3%). BEAS-2B cells exhibited dose-dependent cytotoxicity and cytokine release, while hiPSC-derived lung models showed selective inflammatory responses consistent with human airway pathology. This platform provides an in vitro model that mimics human respiratory physiology, supporting inhalation toxicology and drug screening while reducing reliance on animal testing.