Fabrication and Characterization of 3D Bioprinted Triple-layered Human Alveolar Lung Models.

The global prevalence of respiratory diseases caused by infectious pathogens has resulted in an increased demand for realistic alveolar lung models to serve as suitable disease models. This demand has resulted in the fabrication of numerous two-dimensional (2D) and three-dimensional (3D) alveolar lung models. The ability to fabricate these 3D alveolar lung models in an automated manner with high repeatability and reliability is important for potential scalable production. In this study, we reported the fabrication of human triple-layered alveolar lung models comprising of human lung epithelial cells, human endothelial cells, and human lung fibroblasts using the drop-on-demand (DOD) 3D bioprinting technique. The polyvinylpyrrolidone-based bio-inks and the use of a 300 mm nozzle diameter improved the repeatability of the bioprinting process by achieving consistent cell output over time using different human alveolar lung cells. The 3D bioprinted human triple-layered alveolar lung models were able to maintain cell viability with relative similar proliferation profile over time as compared to non-printed cells. This DOD 3D bioprinting platform offers an attractive tool for highly repeatable and scalable fabrication of 3D human alveolar lung models.