title: Bioengineered vocal fold mucosa for voice restoration.
abstract: Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Changying
authors.initials: C
authors.lastname: Ling
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Qiyao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Brown
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Yo
authors.initials: Y
authors.lastname: Kishimoto
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Toya
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Devine
authors.affiliation: Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Choi
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nishimoto
authors.affiliation: Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Norman
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Tenzin
authors.initials: T
authors.lastname: Tsegyal
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Jiang
authors.affiliation: Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
authors.affiliation: Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Sundaram
authors.initials: S
authors.lastname: Gunasekaran
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Lloyd M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Frey
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. welham@surgery.wisc.edu.
authors.forename: Nathan V
authors.initials: NV
authors.lastname: Welham
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004285:Dogs; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D006085:Graft Survival; D064593:Heterografts; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D010641:Phenotype; D010699:Phonation; D040901:Proteomics / Q000379:methods; D020127:Recovery of Function; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D013997:Time Factors; D023822:Tissue Engineering; D014827:Vocal Cords / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D014831:Voice; D014832:Voice Disorders / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*
chemical_list: D015415:Biomarkers