Abstract

Severevocalfold(VF)mucosalinjuryanditsassociatedvoiceimpairment(dysphonia)isadebilitatingand challengingclinicalproblemwithfewtreatmentoptions,noneofwhichareconsistentlyeffective.Inpatients withsuchtissueimpairmentorloss,anengineeredVFmucosawouldprovideabiomechanicallyappropriate tissuegraftforvoicerestoration.Duringourpreviousfundingcycle,weengineeredsuchaVFmucosavia organotypiccultureofprimaryvocalfoldfibroblastsandepithelialcellsfromhumandonors.Inaseriesof preclinicalexperiments,theengineeredmucosarecapitulatedthestructureandphysiologicfunctionofnative humantissue.Inthecurrentapplication,weproposeanaturalextensionofourpriorworkbyadvancing characterizationoftheinvitrotissueengineeringprocessatthebiologicalsystemlevel(Aim1),studying remodelingandtheadaptiveimmuneresponsetotheengineeredmucosafollowinginvivoheterotopic implantation(Aim2),andstudyinglong-termphysiologicandimmunologicoutcomesfollowinginvivo orthotopicimplantation(Aim3).Theseexperimentswillgenerateimportantpreclinicalsafetyandefficacydata. Wewillcombinetheplannedexperimentalworkwithregulatoryandclinicalmanufacturingmilestones(Aim4), withafinalgoalofholdingapre-InvestigationalNewDrugmeetingwiththeFDAbytheendofthegrant.The tissueengineeringtechnologyoutlinedinthisapplicationhasthepotentialtotransformtreatmentofthemost recalcitrantVFtissuedisordersencounteredintheclinic.

Public Health Relevance

Thegoaloftheproposedresearchistofurtherdevelopandrefineatissueengineeringapproachtocreate replacementvocalfoldtissuesforpatientswithseverelydamagedvocalfolds.Suchpatientshavesignificant voicedifficultieswhichoftencontributetoreducedqualityoflife.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC010777-06
Application #
9176894
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2010-04-01
Project End
2021-07-31
Budget Start
2016-08-20
Budget End
2017-07-31
Support Year
6
Fiscal Year
2016
Total Cost
$582,755
Indirect Cost
$198,336

  Institution

Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Li, Qiyao; Shortreed, Michael R; Wenger, Craig D et al. (2017) Global Post-Translational Modification Discovery. J Proteome Res 16:1383-1390
Thibeault, Susan L; Welham, Nathan V (2017) Strategies for advancing laryngeal tissue engineering. Laryngoscope 127:2319-2320
Gilpin, Sarah E; Li, Qiyao; Evangelista-Leite, Daniele et al. (2017) Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration. Biomaterials 140:212-219
Moore, Jaime E; Rathouz, Paul J; Havlena, Jeffrey A et al. (2016) Practice variations in voice treatment selection following vocal fold mucosal resection. Laryngoscope 126:2505-2512
Li, Qiyao; Chang, Zhen; Oliveira, Gisele et al. (2016) Protein turnover during in vitro tissue engineering. Biomaterials 81:104-113
Kishimoto, Ayami Ohno; Kishimoto, Yo; Young, David L et al. (2016) High- and ultrahigh-field magnetic resonance imaging of naïve, injured and scarred vocal fold mucosae in rats. Dis Model Mech 9:1397-1403
Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun et al. (2016) Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds. Lab Invest 96:807-16
Li, Qiyao; Uygun, Basak E; Geerts, Sharon et al. (2016) Proteomic analysis of naturally-sourced biological scaffolds. Biomaterials 75:37-46
Ling, Changying; Li, Qiyao; Brown, Matthew E et al. (2015) Bioengineered vocal fold mucosa for voice restoration. Sci Transl Med 7:314ra187
Welham, Nathan V; Ling, Changying; Dawson, John A et al. (2015) Microarray-based characterization of differential gene expression during vocal fold wound healing in rats. Dis Model Mech 8:311-21

Showing the most recent 10 out of 16 publications