All-Inkjet-Printed 3D Alveolar Barrier Model with Physiologically Relevant Microarchitecture

With the outbreak of new respiratory viruses and high mortality rates of pulmonary diseases, physiologically relevant models of human respiratory system are urgently needed to study disease pathogenesis, drug efficacy, and pharmaceutics. In this paper, a 3D alveolar barrier model fabricated by printing four human alveolar cell lines, namely, type I and II alveolar cells (NCI-H1703 and NCI-H441), lung fibroblasts (MRC5), and lung microvascular endothelial cells (HULEC-5a) is presented. Automated high-resolution deposition of alveolar cells by drop-on-demand inkjet printing enables to fabricate a three-layered alveolar barrier model with an unprecedented thickness of approximate to 10 mu m. The results show that the 3D structured model better recapitulate the structure, morphologies, and functions of the lung tissue, compared not only to a conventional 2D cell culture model, as expected, but also a 3D non-structured model of a homogeneous mixture of the alveolar cells and collagen. Finally, it is demonstrated that this thin multilayered model reproduce practical tissue-level responses to influenza infection. Drop-on-demand inkjet-printing is an enabling technology for customization, scalable manufacturing, and standardization of their size and growth, and it is believed that this 3D alveolar barrier model can be used as an alternative to traditional test models for pathological and pharmaceutical applications.

Automated summary

Given the urgency to study pathogenesis, drug efficacy, and pharmaceutics in the face of new respiratory viruses and high mortality rates of pulmonary diseases, a 3D alveolar barrier model fabricated by printing human alveolar cell lines is presented in this study. This model, enabled by drop-on-demand inkjet printing technology, can better recapitulate lung tissue structure and function compared to traditional models, showing potential for pathological and pharmaceutical applications.