{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:11:38Z","timestamp":1785456698536,"version":"3.56.0"},"reference-count":83,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp; Transla Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here, a biomimetic in vitro three\u2010dimensional (3D) upper airways model allows to recapitulate lung injury and immune responses induced during invasive mechanical ventilation in neonates. Under such ventilatory support, flow\u2010induced stresses injure the bronchial epithelium of the intubated airways model and directly modulate epithelial cell inflammatory cytokine secretion associated with pulmonary injury. Fluorescence microscopy and biochemical analyses reveal site\u2010specific susceptibility to epithelial erosion in airways from jet\u2010flow impaction and are linked to increases in cell apoptosis and modulated secretions of cytokines IL\u20106, \u20108, and \u201010. In an effort to mitigate the onset of biotrauma, prophylactic pharmacological treatment with Montelukast, a leukotriene receptor antagonist, reduces apoptosis and pro\u2010inflammatory signaling during invasive ventilation of the in vitro model. This 3D airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research toward protective therapies and improved protocols for patient care.<\/jats:p>","DOI":"10.1002\/btm2.10271","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T01:59:56Z","timestamp":1637114396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ventilation\u2010induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti\u2010inflammatory therapeutics"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-1401","authenticated-orcid":false,"given":"Eliram","family":"Nof","sequence":"first","affiliation":[{"name":"Faculty of Biomedical Engineering Technion \u2010 Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-7410","authenticated-orcid":false,"given":"Arbel","family":"Artzy\u2010Schnirman","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering Technion \u2010 Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-9580","authenticated-orcid":false,"given":"Saurabh","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering Technion \u2010 Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Sabatan","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering Technion \u2010 Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6768-0042","authenticated-orcid":false,"given":"Dan","family":"Waisman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Technion \u2010 Israel Institute of Technology  Haifa Israel"},{"name":"Department of Neonatology Carmel Medical Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-7278","authenticated-orcid":false,"given":"Ori","family":"Hochwald","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Technion \u2010 Israel Institute of Technology  Haifa Israel"},{"name":"Department of Neonatology Ruth Rappaport Children's Hospital, Rambam Healthcare  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Gruber","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine Bar\u2010Ilan University  Safed Israel"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Galilee Medical Center  Nahariya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-4308","authenticated-orcid":false,"given":"Liron","family":"Borenstein\u2010Levin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Technion \u2010 Israel Institute of Technology  Haifa Israel"},{"name":"Department of Neonatology Ruth Rappaport Children's Hospital, Rambam Healthcare  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-3842","authenticated-orcid":false,"given":"Josu\u00e9","family":"Sznitman","sequence":"additional","affiliation":[{"name":"Faculty of Biomedical Engineering Technion \u2010 Israel Institute of Technology  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181ef4460"},{"issue":"5","key":"e_1_2_9_3_1","first-page":"646","article-title":"Ventilator\u2010induced lung injury: from barotrauma to biotrauma","volume":"50","author":"Slutsky AS","year":"2005","journal-title":"Respir Care"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.68.072304.113443"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2016.07.019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.6825"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.9611"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-020-00692-6"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"e_1_2_9_10_1","first-page":"9","article-title":"ICU and ventilator mortality among critically ill adults with coronavirus disease 2019","volume":"48","author":"Auld SC","year":"2020","journal-title":"Crit Care Med"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208707"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421801"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30188-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20449-w"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.1.9803046"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2008.09.020"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.1.54"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-004-2363-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012414-040418"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2020.1738380"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004249"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.616830"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.602646"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.5023034"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)30159-X"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00057-6"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770909909087284"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2003.09.024"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medengphy.2014.01.010"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2019.0516"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01179.2001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1542\/9781610020275"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80585-6"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198409000-00035"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-87553-3"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022112001003809"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevFluids.3.103101"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiomech.2017.11.009"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(00)00452-X"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.12.017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-74901-3_10"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-243733"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120436"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712287105"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.fl.09.010177.001305"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000149854.61192.DC"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.96.09071531"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2014.06.008"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/358748"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207711"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02368418"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2009.02.018"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2017.06.003"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1159\/000499361"},{"issue":"2","key":"e_1_2_9_56_1","first-page":"228","article-title":"Comparison of airway pathologic lesions after high\u2010frequency jet or conventional ventilation","volume":"143","author":"Polak MJ","year":"1989","journal-title":"Am J Dis Child"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00361.2009"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1039\/C0LC00251H"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00176807"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/948406"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3109\/03639041003695113"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.683"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2019.1670640"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S50995"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2021.101223"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2019.09.006"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00764.2002"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00989"},{"key":"e_1_2_9_69_1","first-page":"163","article-title":"1 232, respiratory biomechanics","volume":"163","author":"Ghadiali SN","year":"2008","journal-title":"Respir Physiol Neurobiol"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00091"},{"key":"e_1_2_9_71_1","first-page":"758","article-title":"AARC Clinical Practice Guidelines. Endotracheal suctioning of mechanically ventilated patients with artificial airways 2010","volume":"55","author":"American Association for Respiratory Care","year":"2010","journal-title":"Respir Care"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000002324"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2019.03.024"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.72.1.27"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-198101000-00001"},{"key":"e_1_2_9_76_1","first-page":"CD000437","article-title":"Rescue high\u2010frequency jet ventilation versus conventional ventilation for severe pulmonary dysfunction in preterm infants","volume":"10","author":"Rojas\u2010Reyes M","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-802900-8.00009-9"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3181cfc416"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-1-1"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2016.05.012"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2005.01.002"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1159\/000365488"},{"key":"e_1_2_9_83_1","first-page":"25","article-title":"Effect of montelukast on bronchopulmonary dysplasia (BPD) and related mechanisms","volume":"2019","author":"Chen X","year":"1886","journal-title":"Med Sci Monit"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113901"}],"container-title":["Bioengineering &amp; Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.10271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btm2.10271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btm2.10271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:07:42Z","timestamp":1760040462000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btm2.10271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":83,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/btm2.10271"],"URL":"https:\/\/doi.org\/10.1002\/btm2.10271","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/BTM2.10271\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/BTM2.10271\/v2\/decision1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.05.02.441992","asserted-by":"object"}]},"ISSN":["2380-6761","2380-6761"],"issn-type":[{"value":"2380-6761","type":"print"},{"value":"2380-6761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10271"}}