GENERATE A PHYSIOLOGICAL AND COMPLEX PULMONARY TISSUE BY 3D-BIOIMPRESSION FOR THE STUDY OF HOST / PATHOGEN INTERACTIONS – Print-A-Lung

The considerable and rising impact of respiratory diseases worldwide, such as the COVID-19 pandemic, highlights the need to improve in vitro models to predict better and treat such diseases. The Print@Lung project aims to develop a physiologically relevant in vitro model of the human lung for studying host-pathogen interactions and validating therapeutic approaches. The human lung's intricate architecture and biological composition pose a substantial challenge for in vitro modelling. While current advancements in 3D culture techniques, like organoids, show promise, they still lack key elements such as a 3D architecture, vascular network, and immune component. The multidisciplinary Print@Lung consortium aims to recreate lung tissue's complex three-dimensional, multicellular structure using 3D bioprinting technology. The project seeks to accomplish three main objectives : 1) generate a fully functional, differentiated respiratory epithelium at a physiological scale, which 2) integrate vascularized connective tissue and cells specific to the lung immune system, while reproducing the architecture of the different zones of the respiratory tract (alveoli vs bronchioli), 3) utilize this model to investigate host responses to bacterial (S. aureus and P. aeruginosa) and viral (Sars-Cov2) infections, as well as evaluate the effectiveness of various antiviral strategies. Our model functionality will be assessed and compared with reference ALI cultures. The development of such a 3D physiological lung model will provide a valuable tool for understanding the mechanisms of infection, predicting the pathogenicity of emerging microbial strains, and validating the efficacy of treatments. In addition, this complex tissue model is in line with the 3Rs approach, offering an alternative to in vivo experimentation. And over the long term, PRINT@LUNG will forge new avenues for biomedical research, not only in infectious diseases but also in cancer, chronic respiratory diseases, and genetic disorders.