{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:48:00Z","timestamp":1790009280495,"version":"4.0.1"},"reference-count":26,"publisher":"SAGE Publications","issue":"9-10","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tissue Engineering Part A"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bioengineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we developed laryngeal scaffolds which were generated by detergent perfusion-decellularization over 9 days and preserved their glycosaminoglycan content and biomechanical properties of a native larynx. After subcutaneous implantations in rats for 14 days, the scaffolds did not elicit a CD3 lymphocyte response. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated reendothelialized arterial and venous vascular beds. Under the same culture medium, we bioengineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in an intramuscular transplantation model in immunodeficient mice. We supported formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing complex, multicellular, ready-to-transplant tissue grafts.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Impact Statement<\/jats:title>\n                    <jats:p>\n                      For patients undergoing laryngectomy, no reconstruction methods are available to restore the complex functions of the human larynx. The first promising preclinical results have been achieved with the use of biological scaffolds fabricated from decellularized tissue. However, the complexity of laryngeal tissue composition remains a hurdle to create functional viable grafts, since previously each cell type requires tailored culture conditions. In this study, we report the\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      formation of three humanized laryngeal tissue compartments under one uniform culture condition, a possible keystone in creating vital composite tissue grafts for laryngeal regeneration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ten.tea.2019.0128","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T07:34:19Z","timestamp":1572420859000},"page":"543-555","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds"],"prefix":"10.1177","volume":"26","author":[{"given":"Philipp T.","family":"Moser","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Gerli","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Great Ormond Street Institute of Child Health, University College London Medical School, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian R.","family":"Diercks","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Evangelista-Leite","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Charest","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua R.","family":"Gershlak","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Ren","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Gilpin","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard J.","family":"Jank","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn R.","family":"Gaudette","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Hartnick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald C.","family":"Ott","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Department of Thoracic Surgery, Harvard Medical School, Boston, Massachusetts, 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