A research team, with participation from the DZL, has developed an innovative human “lung-on-a-chip” model that realistically replicates key mechanisms of ventilator-associated pneumonia (VAP). The study, published in the Journal of Clinical Investigation, shows that mechanical strain — such as that occurring during mechanical ventilation — can significantly worsen bacterial lung infections.
Ventilator-associated pneumonia is among the most common infections in intensive care units and is associated with high mortality. However, its pathophysiology remains insufficiently understood, partly due to the lack of suitable models. To address this gap, the researchers developed a so-called “pneumonia-on-a-chip” system. This system is based on a microfluidic lung model that mimics the alveolar-capillary interface, air–liquid transitions, and the mechanical stretching movements of breathing. Primary human lung cells were used, including alveolar epithelial and endothelial cells.
The key finding: Increased mechanical strain, comparable to more intensive ventilation, made lung tissue more susceptible to infection with Pseudomonas aeruginosa, a typical pathogen in VAP. Under higher strain, the cells exhibited an altered immune response and increased bacterial colonization.
The model was also able to reproduce important disease processes, including bacterial colonization and virulence mechanisms that are critical for the progression of pneumonia.
The study provides important evidence that mechanical factors, particularly ventilation parameters, can actively contribute to the worsening of lung infections. At the same time, it highlights the potential of modern organ-on-a-chip technologies to investigate complex disease mechanisms under physiologically relevant conditions.
Such models could help optimize ventilation strategies and support the targeted development of new therapeutic approache, especially for critically ill patients in intensive care units.
Original publication:
Hoffmann, Karen; Behrendt, Ulrike; Pennitz, Peter; Kirsten, Holger; Pohl, Jessica; Lopez-Rodriguez, Elena et al. (2026): Mechanical strain exacerbates Pseudomonas infection in an organoid-based pneumonia-on-a-chip model. In: The Journal of clinical investigation 136 (2). DOI: 10.1172/JCI192454.
