{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:12:52Z","timestamp":1782889972642,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the effectiveness of scaffold\u2010embedded mesenchymal stem cells (MSCs) as a topical treatment for healing tympanic membrane perforations (TMPs) in a mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Prospective animal study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Experimental.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>In vitro: under sterile conditions, porcine\u2010derived (Gelita\u2010Spon [GS]), hyaluronate\u2010derived (EpiDisc [ED]), and polyvinyl alcohol (PVA) scaffolds were cut into small pieces and cocultured with murine bone marrow\u2013derived MSCs (BM\u2010MSCs) expressing green fluorescent protein (GFP) for 72 hours. The cultures were either analyzed by confocal microscopy or used for subsequent in vivo experiments. In vivo: 26\u00a0mice were divided into 3\u00a0groups (ie, control [n = 9], GS [n = 8], ED [n = 9]). Under general anesthesia, TMPs of equal sizes were performed bilaterally using a sterile 27\u2010gauge needle under a surgical microscope. The BM\u2010MSCs embedded within GS or ED scaffolds were soaked in phosphate\u2010buffered saline and then topically applied on right TMPs, and scaffolds alone were applied on left TMPs 6 to 8 hours after injury. Control mice did not receive treatment. On day 7, animals were euthanized and bullae were harvested for histological analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro: BM\u2010MSCs grew well on both GS (<jats:italic>P =<\/jats:italic>. 0012) and ED (<jats:italic>P =<\/jats:italic>. 0001) scaffolds compared with PVA. In vivo: 100% of untreated (control) TMPs remained open after 7\u00a0days. Animals treated with MSC\u2010embedded ED scaffolds had a higher percentage of TMP closure (<jats:italic>P =<\/jats:italic>. 016) and a thicker neotympanum (<jats:italic>P =<\/jats:italic>. 0033) than control animals. The experimentally applied BM\u2010MSCs engrafted and differentiated into epithelial cells suggested by the colocalized expression of cytokeratin\u201019 and GFP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The topical application of bone marrow\u2013derived MSCs enhances the healing of TMPs in this animal model and is a promising alternative to tympanoplasty.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599816636845","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T22:19:28Z","timestamp":1458080368000},"page":"1106-1114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Effects of Cell\u2010Based Therapy for Treating Tympanic Membrane Perforations in Mice"],"prefix":"10.1002","volume":"154","author":[{"given":"Stefania","family":"Goncalves","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery University 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