Advancement of a Physiologically Relevant 3D Lung Model through One-Stage DLP Bioprinting for the Study of Lung Diseases

Developing a lung-on-a-chip (LOC) platform that is both physiologically and pathologically relevant is crucial due to the mortality and recurrent pandemics of zoonotically transmitted pathogens. This study reports the fabrication of an LOC with an intrinsic air-liquid interface (ALI) via a digital light processing (DLP) 3D bioprinter. The platform architecture supports the localization of different cells, such as human lung epithelial cells (HLEC), human fibroblasts, and human endothelial cells, to mimic their in vivo counterparts. While the air layer of the LOC undergoes cyclic air-breathing via a custom-built lung bioreactor device, the epithelial cells in the LOC express relevant physiological proteins such as aquaporin 5, E-cadherin, and prosurfactant C. Furthermore, the platform incorporates a dynamic perfusion system in the liquid layer of the LOC, which improves the viability of the cells in the inner core of the 3D model and enhances the expression of V-Cadherin and VEGF-A. We mimicked the infection of the airborne SARS-CoV-2 virus to replicate the disease characteristics of the lungs during SARS-CoV-2 infection by the expression of CoV-NP and OAS1 as an innate response to the viral infection. Incorporating the endothelial layer, ALI, 3D hydrogel, air-induced 3D stretching, and airborne viral infection enhances the physiological relevance of the platform, making it an attractive option for respiratory preclinical testing.