The project aimed at developing a novel cystic fibrosis model (CF) into a microfluidic chip, suitable for tissue culture, monitoring and drug administration. In contrast to the gold standard CF models, in which the epithelium is placed on a polymeric membrane, our 3D pulmonary model is composed by a human bronchial epithelium grown and differentiated on a connective airway tissue, developed by advanced tissue engineering strategies. The model showed positivity for the typical markers of tissue differentiation, and it was useful for the study of epithelial/stromal crosstalk in CF. In fact, the CF connective airway tissue showed differences in comparison with a normal one, such as increased fibroblast activity and production of an abundant and dense extracellular matrix presenting a higher stiffness. The close interaction between the epithelium and the physiologically relevant connective tissue allowed the formation of epithelial gland-like structures, which have a role in the production of the apical fluid whose composition is altered in CF. Indeed, apical mucus viscosity was higher in 3D than in the gold standard CF model. Moreover, transcriptomic analyses showed the up-regulation of genes involved in tissue remodeling and inflammatory response in 3D, which are key factors involved in the evolution of the pathology. The dynamic culture on chip allowed the fast differentiation of CF models and the time-controlled release of drugs. Therefore, the results of the study showed the development of a new CF model useful for the study of the disease and for the screening of drugs targeting CFTR but also tissue remodeling and inflammation occurring in CF.

Pubblications

• Mazio C et al., Intrinsic Abnormalities of Cystic Fibrosis Airway Connective Tissue Revealed by an In Vitro 3D Stromal Model, Cells vol. 9,6 1371. 1 Jun. 2020,