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

¹ Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore

² HP-NTU Digital Manufacturing Corporate Lab, 65 Nanyang Avenue, 637460, Singapore

³ Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, 117510, Singapore

⁴ Lee Kong Chian School of Medicine, Novena Campus, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore

†These authors contributed equally to this work.

IJB 2021, 7(2), 332 https://doi.org/10.18063/ijb.v7i2.332

© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

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 µm 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.

Keywords

3D bioprinting

3D printing

Biofabrication

Lung bioprinting

In-vitro human tissue models

Drop-on-demand

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