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Article

Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors

1
Department of Applied Biochemistry, Technische Universität Berlin, Chair of Applied Biochemistry, 10623 Berlin, Germany
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Department of Internal Medicine/Infectious and Respiratory Diseases, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
3
Department of Organic Chemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Margaret Scull
Viruses 2021, 13(8), 1590; https://doi.org/10.3390/v13081590
Received: 14 July 2021 / Revised: 5 August 2021 / Accepted: 7 August 2021 / Published: 11 August 2021
(This article belongs to the Special Issue The Application of 3D Tissue Culture Systems in Virology)
Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses. View Full-Text
Keywords: bioprinting; human lung model; influenza A virus; LPS stimulation bioprinting; human lung model; influenza A virus; LPS stimulation
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MDPI and ACS Style

Berg, J.; Weber, Z.; Fechler-Bitteti, M.; Hocke, A.C.; Hippenstiel, S.; Elomaa, L.; Weinhart, M.; Kurreck, J. Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors. Viruses 2021, 13, 1590. https://doi.org/10.3390/v13081590

AMA Style

Berg J, Weber Z, Fechler-Bitteti M, Hocke AC, Hippenstiel S, Elomaa L, Weinhart M, Kurreck J. Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors. Viruses. 2021; 13(8):1590. https://doi.org/10.3390/v13081590

Chicago/Turabian Style

Berg, Johanna, Zia Weber, Mona Fechler-Bitteti, Andreas C. Hocke, Stefan Hippenstiel, Laura Elomaa, Marie Weinhart, and Jens Kurreck. 2021. "Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors" Viruses 13, no. 8: 1590. https://doi.org/10.3390/v13081590

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