3D pulmonary fibrosis model for anti-fibrotic drug discovery by inkjet-bioprinting

Abstract

Pulmonary fibrosis (PF) is known as a chronic and irreversible disease characterized by excessive extracellular matrix accumulation and lung architecture changes. Large efforts have been made to develop prospective treatments and study the etiology of pulmonary fibrotic diseases utilizing animal models and spherical organoids. As part of these efforts, we created an all-inkjet-printed three-dimensional (3D) alveolar barrier model that can be used for anti-fibrotic drug discovery. Then, we developed a PF model by treating the 3D alveolar barrier with pro-fibrotic cytokine and confirmed that it is suitable for the fibrosis model by observing changes in structural deposition, pulmonary function, epithelial-mesenchymal transition, and fibrosis markers. The model was tested with two approved anti-fibrotic drugs, and we could observe that the symptoms in the disease model were alleviated. Consequently, structural abnormalities and changes in mRNA expression were found in the induced fibrosis model, which were shown to be recovered in all drug treatment groups. The all-inkjet-printed alveolar barrier model was reproducible for disease onset and therapeutic effects in the human body. This finding emphasized that the in vitro artificial tissue with faithfully implemented 3D microstructures using bioprinting technology may be employed as a novel testing platform and disease model to evaluate potential drug efficacy.