{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:46:45Z","timestamp":1790635605105,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011500","name":"Research Institute, Nationwide Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Humans receiving tissue\u2010engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Large animal model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Pediatric academic research institute.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>Human scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow\u2013derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4\u2010month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All animals had signs of graft stenosis. Three of 5 animals (60%) designated for long\u2010term surveillance survived until the 4\u2010month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In our ovine model, clinically applied synthetic tissue\u2010engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599819844754","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T05:45:35Z","timestamp":1556603135000},"page":"458-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Factors Influencing Poor Outcomes in Synthetic Tissue\u2010Engineered Tracheal Replacement"],"prefix":"10.1002","volume":"161","author":[{"given":"Victoria","family":"Pepper","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery Loma Linda Children\u2019s Hospital Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron A.","family":"Best","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine Research Institute at Nationwide Children\u2019s Hospital Columbus Ohio USA"},{"name":"Biomedical Sciences Graduate Program College of Medicine The Ohio State University Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaila","family":"Buckley","sequence":"additional","affiliation":[{"name":"Department of Pathology The Ohio State University Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Texas Tech University Health Sciences Center Lubbock Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekene","family":"Onwuka","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Ohio State 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