Towards new preclinical respiratory models

Yoann Montigaud


Background: Assessment of aerosol deposition patterns into the lungs remains challenging despite the various models previously developed. Indeed, in vitro studies are barely transposable. In vivo experiments using radiolabelled aerosols are the gold standard but suffer from ethical restrictions. Some computational models have been developed to overcome these limitations, but they are based on extrapolations from healthy patients’ data.

Methods: Our work aimed to develop easy-to-use, reliable and relevant ex vivo respirtory models to precisely cartography and quantify deposition patterns. Our models were composed of 3D-printed Ear-Nose-Throat (ENT) replicas of adult and paediatric patients connected to respitatory tracts placed in sealed enclosures. Passive ventilation could be achieved by mimicking pleural depressions in the enclosure with a depression generation, while invasive ventilation was simulated by the mean of a medical ventilator. Regional ventilation of breathing models was assessed by 81mkrypton scintigraphies. Quantitative cartography of aerosol deposited in the models was carried out by nebulization of a radioaerosol and analyzed with clinical gamma-cameras.

Results: We successfully developed and validated healthy and pathological breathing models showing physiological features that were similar to in vivo patients’ data. Ventilation and deposition patterns were comparable to existing data in literature.

Conclusions: This work demonstrated that these original ex vivo models could be a reliable and relevant tool for regional aerosol depositions studies with less ethical restrictions. We hope that our models would accelerate and facilitate the development of pulmonary delivery strategies by offering an interesting and cost-effective alternative to animal and in vitro studies.

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