{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:39:31Z","timestamp":1787611171937,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Excellence Strategy of the Federal Government and the L\u00e4nder by the Berlin University Alliance","award":["ProTUTec"],"award-info":[{"award-number":["ProTUTec"]}]},{"name":"Excellence Strategy of the Federal Government and the L\u00e4nder by the Berlin University Alliance","award":["EZ-2020-597-2"],"award-info":[{"award-number":["EZ-2020-597-2"]}]},{"DOI":"10.13039\/501100006764","name":"internal funding instrument ProTUTec of the Technische Universit\u00e4t Berlin","doi-asserted-by":"publisher","award":["ProTUTec"],"award-info":[{"award-number":["ProTUTec"]}],"id":[{"id":"10.13039\/501100006764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006764","name":"internal funding instrument ProTUTec of the Technische Universit\u00e4t Berlin","doi-asserted-by":"publisher","award":["EZ-2020-597-2"],"award-info":[{"award-number":["EZ-2020-597-2"]}],"id":[{"id":"10.13039\/501100006764","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Einstein Foundation Berlin","award":["ProTUTec"],"award-info":[{"award-number":["ProTUTec"]}]},{"name":"Einstein Foundation Berlin","award":["EZ-2020-597-2"],"award-info":[{"award-number":["EZ-2020-597-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Viral lung infections are a never-ending threat to public health due to the emergence of new variants and their seasonal nature. While vaccines offer some protection, the need for effective antiviral drugs remains high. The existing research methods using 2D cell culture and animal models have their limitations. Human cell-based tissue engineering approaches hold great promise for bridging this gap. Here, we describe a microextrusion bioprinting approach to generate three-dimensional (3D) lung models composed of four cell types: endothelial cells, primary fibroblasts, macrophage cells, and epithelial cells. A549 and Calu-3 cells were selected as epithelial cells to simulate the cells of the lower and upper respiratory tract, respectively. Cells were bioprinted in a hydrogel consisting of alginate, gelatin, hyaluronic acid, collagen, and laminin-521. The models were cultured under air\u2013liquid interface (ALI) conditions to further enhance their physiological relevance as lung cells. Their viability, metabolic activity, and expression of specific cell markers were analyzed during long-term culture for 21 days. The constructs were successfully infected with both a seasonal influenza A virus (IAV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, demonstrating their potential for studying diverse viral infections.<\/jats:p>","DOI":"10.3390\/ijms26125543","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"5543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bioprinted Four-Cell-Type Lung Model for Viral Infection Studies Under Air\u2013Liquid Interface Conditions"],"prefix":"10.3390","volume":"26","author":[{"given":"Johanna","family":"Berg","sequence":"first","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Heinze","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Institute of Virology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-6365","authenticated-orcid":false,"given":"Daniela","family":"Niemeyer","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Institute of Virology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefin","family":"Hellgren","sequence":"additional","affiliation":[{"name":"Cellink, L\u00e5ngfilsgatan 1-7, 412 77 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himjyot","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Cellink, L\u00e5ngfilsgatan 1-7, 412 77 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-731X","authenticated-orcid":false,"given":"Anna","family":"L\u00f6wa","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hocke","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itedale","family":"Namro","sequence":"additional","affiliation":[{"name":"Cellink, L\u00e5ngfilsgatan 1-7, 412 77 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Drosten","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Charit\u00e9platz 1, 10117 Berlin, Germany"},{"name":"Institute of Virology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-0052","authenticated-orcid":false,"given":"Jens","family":"Kurreck","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-7503","authenticated-orcid":false,"given":"Beatrice","family":"Tolksdorf","sequence":"additional","affiliation":[{"name":"Department of Applied Biochemistry, Institute of Biotechnology, Technische Universit\u00e4t Berlin, 10623 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"L338","DOI":"10.1152\/ajplung.00261.2022","article-title":"World Lung Day: Impact of \u201cthe big 5 lung diseases\u201d in the context of COVID-19","volume":"323","author":"Cohen","year":"2022","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e01031-17","DOI":"10.1128\/JVI.01031-17","article-title":"Complexities of Viral Mutation Rates","volume":"92","author":"Peck","year":"2018","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1128\/JVI.00694-10","article-title":"Belshaw, Viral Mutation Rates","volume":"84","author":"Nebot","year":"2010","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chakraborty, C., Bhattacharya, M., and Dhama, K. (2023). SARS-CoV-2 Vaccines, Vaccine Development Technologies, and Significant Efforts in Vaccine Development during the Pandemic: The Lessons Learned Might Help to Fight against the Next Pandemic. Vaccines, 11.","DOI":"10.3390\/vaccines11030682"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cmi.2021.10.005","article-title":"Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: A narrative review","volume":"28","author":"Fiolet","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rijsbergen, L.C., van Dijk, L.L.A., Engel, M.F.M., de Vries, R.D., and de Swart, R.L. (2021). In Vitro Modelling of Respiratory Virus Infections in Human Airway Epithelial Cells\u2014A Systematic Review. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.683002"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00418-018-1747-9","article-title":"The micromechanics of lung alveoli: Structure and function of surfactant and tissue components","volume":"150","author":"Knudsen","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1016\/j.biocel.2013.08.009","article-title":"Alveolar epithelial cells: Master regulators of lung homeostasis","volume":"45","author":"Guillot","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/v20801530","article-title":"Animal Models for Influenza Virus Pathogenesis and Transmission","volume":"2","author":"Bouvier","year":"2010","journal-title":"Viruses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?","volume":"4","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/biostatistics\/kxx069","article-title":"Estimation of clinical trial success rates and related parameters","volume":"20","author":"Wong","year":"2019","journal-title":"Biostatistics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D1080","DOI":"10.1093\/nar\/gkv1192","article-title":"WITHDRAWN\u2014A resource for withdrawn and discontinued drugs","volume":"44","author":"Siramshetty","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.15252\/emmm.201506025","article-title":"Defining the optimal animal model for translational research using gene set enrichment analysis","volume":"8","author":"Weidner","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_14","first-page":"576","article-title":"3D engineered tissue models for studying human-specific infectious viral diseases","volume":"21","author":"Hwang","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.bj.2020.11.009","article-title":"3D culture models to study SARS-CoV-2 infectivity and antiviral candidates: From spheroids to bioprinting","volume":"44","author":"Melo","year":"2020","journal-title":"Biomed. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.phrs.2018.11.002","article-title":"3D organ models-Revolution in pharmacological research?","volume":"139","author":"Weinhart","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zscheppang, K., Berg, J., Hedtrich, S., Verheyen, L., Wagner, D.E., Suttorp, N., Hippenstiel, S., and Hocke, A.C. (2018). Human Pulmonary 3D Models For Translational Research. Biotechnol. J., 13.","DOI":"10.1002\/biot.201700341"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bejoy, A.M., Makkithaya, K.N., Hunakunti, B.B., Hegde, A., Krishnamurthy, K., Sarkar, A., Lobo, C.F., Keshav, D.V.S., Dharshini, G., and Dharshini, S.D. (2021). An insight on advances and applications of 3d bioprinting: A review. Bioprinting, 24.","DOI":"10.1016\/j.bprint.2021.e00176"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Berg, J., Weber, Z., Fechler-Bitteti, M., Hocke, A.C., Hippenstiel, S., Elomaa, L., Weinhart, M., and Kurreck, J. (2021). Bioprinted Multi-Cell Type Lung Model for the Study of Viral Inhibitors. Viruses, 13.","DOI":"10.3390\/v13081590"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Berg, J., Hiller, T., Kissner, M.S., Qazi, T.H., Duda, G.N., Hocke, A.C., Hippenstiel, S., Elomaa, L., Weinhart, M., and Fahrenson, C. (2018). Optimization of cell-laden bioinks for 3D bioprinting and efficient infection with influenza A virus. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31880-x"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ali, A.S.M., Berg, J., Roehrs, V., Wu, D., Hackethal, J., Braeuning, A., Woelken, L., Rauh, C., and Kurreck, J. (2024). Xeno-Free 3D Bioprinted Liver Model for Hepatotoxicity Assessment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031811"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, D., Berg, J., Arlt, B., R\u00f6hrs, V., Al-Zeer, M.A., Deubzer, H.E., and Kurreck, J. (2021). Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010122"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2314171","DOI":"10.1002\/adfm.202314171","article-title":"Bioprinting of Perfusable Vascularized Organ Models for Drug Development via Sacrificial-Free Direct Ink Writing","volume":"34","author":"Wu","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mahfouzi, S.H., Tali, S.H.S., and Amoabediny, G. (2021). 3D bioprinting for lung and tracheal tissue engineering: Criteria, advances, challenges, and future directions. Bioprinting, 21.","DOI":"10.1016\/j.bprint.2020.e00124"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Xu, J., Wei, Y., Zou, S., and Ye, J. (2023). Characterization of 3D-Bioprinted In Vitro Lung Cancer Models Using RNA-Sequencing Techniques. Bioengineering, 10.","DOI":"10.3390\/bioengineering10060667"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sanchez-Guzman, D., Boland, S., Brookes, O., Mc Cord, C., Lai Kuen, R., Sirri, V., Baeza Squiban, A., and Devineau, S. (2021). Long-Term Evolution of the Epithelial Cell Secretome in Preclinical 3D Models of the Human Bronchial Epithelium. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-86037-0"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.4049\/jimmunol.182.3.1296","article-title":"Differentiated Human Alveolar Type II Cells Secrete Antiviral IL-29 (IFN-\u03bb1) in Response to Influenza A Infection","volume":"182","author":"Wang","year":"2009","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wiese-Rischke, C., Murkar, R.S., and Walles, H. (2021). Biological Models of the Lower Human Airways\u2014Challenges and Special Requirements of Human 3D Barrier Models for Biomedical Research. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122115"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11684-020-0754-0","article-title":"Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection","volume":"14","author":"Zou","year":"2020","journal-title":"Front. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S2666-5247(20)30004-5","article-title":"Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study","volume":"1","author":"Chu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Niemeyer, D., M\u00f6sbauer, K., Klein, E.M., Sieberg, A., Mettelman, R.C., Mielech, A.M., Dijkman, R., Baker, S.C., Drosten, C., and M\u00fcller, M.A. (2018). The papain-like protease determines a virulence trait that varies among members of the SARS-coronavirus species. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007296"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","article-title":"Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR","volume":"25","author":"Corman","year":"2020","journal-title":"Euro Surveill."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Are, E.B., Song, Y., Stockdale, J.E., Tupper, P., and Colijn, C. (2023). COVID-19 endgame: From pandemic to endemic? Vaccination, reopening and evolution in low- and high-vaccinated populations. J. Theor. Biol., 559.","DOI":"10.1016\/j.jtbi.2022.111368"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rabaan, A.A., Al-Ahmed, S.H., Albayat, H., Alwarthan, S., Alhajri, M., Najim, M.A., AlShehail, B.M., Al-Adsani, W., Alghadeer, A., and Abduljabbar, W.A. (2023). Variants of SARS-CoV-2: Influences on the Vaccines\u2019 Effectiveness and Possible Strategies to Overcome Their Consequences. Medicina, 59.","DOI":"10.3390\/medicina59030507"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.molmed.2012.05.003","article-title":"In vivo veritas, in vitro artificial","volume":"18","author":"Matarese","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1749-6632.2009.04972.x","article-title":"Toward a durable anti-HIV gene therapy based on RNA interference","volume":"1175","author":"Berkhout","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/infdis\/jiu504","article-title":"Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice","volume":"211","author":"Stein","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.omtn.2017.07.002","article-title":"Anti-adenoviral Artificial MicroRNAs Expressed from AAV9 Vectors Inhibit Human Adenovirus Infection in Immunosuppressed Syrian Hamsters","volume":"8","author":"Schaar","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1002\/1873-3468.13647","article-title":"MiR-375-mediated suppression of engineered coxsackievirus B3 in pancreatic cells","volume":"594","author":"Pryshliak","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105879","DOI":"10.1016\/j.antiviral.2024.105879","article-title":"Development of a highly stable, active small interfering RNA with broad activity against SARS-CoV viruses","volume":"226","author":"Tolksdorf","year":"2024","journal-title":"Antiviral Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tolksdorf, B., Nie, C., Niemeyer, D., R\u00f6hrs, V., Berg, J., Lauster, D., Adler, J.M., Haag, R., Trimpert, J., and Kaufer, B. (2021). Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence. Viruses, 13.","DOI":"10.3390\/v13102030"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1038\/s41467-020-18319-6","article-title":"Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gard, A.L., Luu, R.J., Miller, C.R., Maloney, R., Cain, B.P., Marr, E.E., Burns, D.M., Gaibler, R., Mulhern, T.J., and Wong, C.A. (2021). High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-94095-7"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zarkoob, H., Allu\u00e9-Guardia, A., Chen, Y.-C., Garcia-Vilanova, A., Jung, O., Coon, S., Song, M.J., Park, J.-G., Oladunni, F., and Miller, J. (2022). Modeling SARS-CoV-2 and influenza infections and antiviral treatments in human lung epithelial tissue equivalents. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03753-7"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12931-025-03095-y","article-title":"Optimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2","volume":"26","author":"Sen","year":"2025","journal-title":"Respir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Goh, K.J., Lu, H., Tan, E.K., Lee, Z.Y., Wong, A., Tran, T., Dunn, N.R., and Roy, S. (2024). Differentiation of CD166-positive hPSC-derived lung progenitors into airway epithelial cells. Biol. Open, 13.","DOI":"10.1242\/bio.061729"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jensen, C., and Teng, Y. (2020). Is It Time to Start Transitioning From 2D to 3D Cell Culture?. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00033"},{"key":"ref_48","first-page":"269","article-title":"Clean bioprinting\u2014Fabrication of 3D organ models devoid of animal components","volume":"38","author":"Berg","year":"2021","journal-title":"ALTEX"},{"key":"ref_49","first-page":"293","article-title":"Kinetic profile of influenza virus infection in three rat strains","volume":"53","author":"Daniels","year":"2003","journal-title":"Comp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/nm1280","article-title":"Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque","volume":"11","author":"Li","year":"2005","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/j.ymthe.2021.05.004","article-title":"A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19","volume":"29","author":"Idris","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.omtn.2023.05.016","article-title":"Lipid nanoparticle-encapsulated, chemically modified anti-adenoviral siRNAs inhibit hepatic adenovirus infection in immunosuppressed Syrian hamsters","volume":"32","author":"Geisler","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E2165","DOI":"10.1073\/pnas.1209182109","article-title":"Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B","volume":"109","author":"Sitia","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1038\/s41591-019-0560-x","article-title":"A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model","volume":"25","author":"Yant","year":"2019","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1111\/exd.14327","article-title":"Herpes simplex virus 1 proteins can induce skin inflammation in an atopic dermatitis-like mouse model","volume":"30","author":"Novak","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.cell.2020.06.011","article-title":"A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies","volume":"182","author":"Hassan","year":"2020","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.cell.2020.06.010","article-title":"Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment","volume":"182","author":"Sun","year":"2020","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Moysidou, C.-M., Barberio, C., and Owens, R.M. (2021). Advances in Engineering Human Tissue Models. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.620962"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Karamchand, L., Makeiff, D., Gao, Y., Azyat, K., Serpe, M.J., and Kulka, M. (2023). Biomaterial inks and bioinks for fabricating 3D biomimetic lung tissue: A delicate balancing act between biocompatibility and mechanical printability. Bioprinting, 29.","DOI":"10.1016\/j.bprint.2022.e00255"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zimmerling, A., and Chen, X. (2020). Bioprinting for combating infectious diseases. Bioprinting, 20.","DOI":"10.1016\/j.bprint.2020.e00104"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Zimmerling, A., Dahlan, N.A., Zhou, Y., and Chen, X. (2024). Recent frontiers in biofabrication for respiratory tissue engineering. Bioprinting, 40.","DOI":"10.1016\/j.bprint.2024.e00342"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, Z., Lam, E.H.Y., Yu, F., and Zhu, S. (2023). 3D Bioprinting for Next-Generation Personalized Medicine. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076357"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1177\/2211068214557813","article-title":"Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening","volume":"20","author":"Nam","year":"2015","journal-title":"J. Lab. Autom."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.apsb.2018.03.006","article-title":"3D tissue engineering, an emerging technique for pharmaceutical research","volume":"8","author":"Jensen","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.stem.2020.10.004","article-title":"Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2","volume":"27","author":"Youk","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-020-3014-1","article-title":"Progenitor identification and SARS-CoV-2 infection in human distal lung organoids","volume":"588","author":"Salahudeen","year":"2020","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41551-021-00718-9","article-title":"A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics","volume":"5","author":"Si","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lee, Y., Lee, M.K., Lee, H.-R., Kim, B., Kim, M., and Jung, S. (2024). 3D-printed airway model as a platform for SARS-CoV-2 infection and antiviral drug testing. Biomaterials, 311.","DOI":"10.1016\/j.biomaterials.2024.122689"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6822","DOI":"10.1073\/pnas.1806308115","article-title":"Differentiated human airway organoids to assess infectivity of emerging influenza virus","volume":"115","author":"Zhou","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jviromet.2018.12.017","article-title":"Enhanced in vitro virus expression using 3-dimensional cell culture spheroids for infection","volume":"265","author":"Rosellini","year":"2019","journal-title":"J. Virol. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/aor.13880","article-title":"Spheroids and organoids as humanized 3D scaffold-free engineered tissues for SARS-CoV-2 viral infection and drug screening","volume":"45","author":"Kronemberger","year":"2021","journal-title":"Artif. Organs"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.bbrc.2021.09.015","article-title":"Air-liquid interphase culture confers SARS-CoV-2 susceptibility to A549 alveolar epithelial cells","volume":"577","author":"Sasaki","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4062\/biomolther.2020.226","article-title":"Differential Signaling and Virus Production in Calu-3 Cells and Vero Cells upon SARS-CoV-2 Infection","volume":"29","author":"Park","year":"2021","journal-title":"Biomol. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e29579","DOI":"10.1002\/jmv.29579","article-title":"The use of human iPSC-derived alveolar organoids to explore SARS-CoV-2 variant infections and host responses","volume":"96","author":"Gandikota","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Fisher, C.R., Medie, F.M., Luu, R.J., Gaibler, R.B., Mulhern, T.J., Miller, C.R., Zhang, C.J., Rubio, L.D., Marr, E.E., and Vijayakumar, V. (2023). A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening. Cells, 12.","DOI":"10.3390\/cells12222639"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41579-021-00542-7","article-title":"Influenza virus and SARS-CoV-2: Pathogenesis and host responses in the respiratory tract","volume":"19","author":"Flerlage","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316","article-title":"The Pathology of Influenza Virus Infections","volume":"3","author":"Taubenberger","year":"2008","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12985-019-1146-4","article-title":"Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures","volume":"16","author":"Chen","year":"2019","journal-title":"Virol. J."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Yeo, M., Sarkar, A., Singh, Y.P., Derman, I.D., Datta, P., and Ozbolat, I.T. (2024). Synergistic coupling between 3D bioprinting and vascularization strategies. Biofabrication, 16.","DOI":"10.1088\/1758-5090\/ad0b3f"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1093\/infdis\/jis455","article-title":"Influenza A Viruses Target Type II Pneumocytes in the Human Lung","volume":"206","author":"Weinheimer","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Niemeyer, D., Stenzel, S., Veith, T., Schroeder, S., Friedmann, K., Weege, F., Trimpert, J., Heinze, J., Richter, A., and Jansen, J. (2022). SARS-CoV-2 Variant Alpha Has a Spike-Dependent Replication Advantage over the Ancestral B.1 Strain in Human Cells with Low ACE2 Expression. PLOS Biol., 20.","DOI":"10.1371\/journal.pbio.3001871"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"L263","DOI":"10.1152\/ajplung.00141.2021","article-title":"A toolbox for studying respiratory viral infections using air-liquid interface cultures of human airway epithelial cells","volume":"321","author":"Michi","year":"2021","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wu, N.-H., Yang, W., Beineke, A., Dijkman, R., Matrosovich, M., Baumg\u00e4rtner, W., Thiel, V., Valentin-Weigand, P., Meng, F., and Herrler, G. (2016). The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells. Sci. Rep., 6.","DOI":"10.1038\/srep39668"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:29Z","timestamp":1760032169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":83,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125543"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125543","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}