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

Ng, Wei Long; Ayi, Teck Choon; Liu, Yi-Chun; Sing, Swee Leong; Yeong, Wai Yee; Tan, Boon-Huan

The global prevalence of respiratory diseases caused by infectious pathogens has resulted in an increased demand for realistic in-vitro 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) in-vitro alveolar lung models. The ability to fabricate these 3D in-vitro 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 in-vitro human alveolar lung models.