{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:47Z","timestamp":1792088027117,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2976\/20"],"award-info":[{"award-number":["2976\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Most tympanic membrane (TM) perforations heal spontaneously, but 10%\u201320% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1\u2010antitrypsin (AAT) is a circulating tissue\u2010protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to examine the effects of local clinical\u2010grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>\u2009mL at 20\u2009mg\/mL on days 0, 1, and 2; <jats:italic>n<\/jats:italic>\u2009=\u200915\/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post\u2010injury, and TMs were excised for gene analysis by RT\u2010PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no adverse reactions in hAAT\u2010treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median: 4 and 9, respectively). According to gene expression analysis, VEGF, TGF\u03b2, and collagen\u20105A1 were induced earlier in AAT\u2010treated mice (day 4\u20135 compared with day 9). Additionally, IL\u201010 expression levels were higher and IL\u20106 levels were lower in treated versus untreated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro\u2010dosing in the format of a single local application.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 134:3802\u20133806, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31454","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T05:53:17Z","timestamp":1713851597000},"page":"3802-3806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Local Alpha1\u2010Antitrypsin Accelerates the Healing of Tympanic Membrane Perforation in Mice"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-7554","authenticated-orcid":false,"given":"Sabri","family":"El\u2010Saied","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Soroka University Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Amar","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Soroka University Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Shitrit","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3609-1591","authenticated-orcid":false,"given":"Benyamin M.","family":"Kaminer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Soroka University Medical Center  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aharon","family":"Keshet","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli C.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences Ben\u2010Gurion University of the Negev  Beer\u2010Sheva 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