Vocal fold scarring is the single greatest cause of poor voice after vocal fold surgery (Hirano, 1995;Woo, Casper, Colton and Brewer, 1994). Such scarring results in replacement of healthy tissue by fibrous tissue, which can irrevocably alter vocal fold function, leading to a decreased or absent vocal fold mucosal wave (Benninger, Alessi, Archer et al., 1996). Even small foci of scar can impede vocal fold function when separation of the body (muscle) and cover (epithelium and the superficial layer of the lamina propria) is compromised. Because there is currently no consistently effective treatment for the scarred vocal fold, it is 1 of the most challenging laryngeal disorders to treat (Thibeault and Ford, 2003) and is the focus of this competing renewal on characterizing taryngeal scars. The long-range aim of this project no longer focuses exclusively on sulcus vocalis, but now encompasses the characterization and treatment of the more universal phenomenon of vocal fold scarring. This long-range objective will be accomplished by characterizing laryngeal scarring and its influence on phonation, both pre-and post-treatment, using 1) controlled laboratory experiments, and 2) computer modeling experiments. The laboratory experiments will investigate treatment effects at the cellular level in animal's tissues and excised larynx models. Building on experiments completed over the last 5 years, we will investigate the role of growth factors and vitamin A in preventing and treating scars, and we will attempt to better characterize scars in the vocal fold and their vibratory consequences. We have found it necessary to combine modeling and systematic laboratory investigations to resolve the complex interactions between tissue characteristics, geometry and surgical requisites necessary to create a suitable clinical outcome. This proposal is timely because no consistently effective treatment modality is known for scarring, and it remains 1 of the unsolved problems of phonosurgery. While our initial 5 years of study have yielded several key hypotheses to guide treatment options, the current proposal will enable us to substantiate and/or further clarify these hypotheses so that they will have a greater impact.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004428-09
Application #
7642403
Study Section
Special Emphasis Panel (ZRG1-BBBP-E (02))
Program Officer
Shekim, Lana O
Project Start
2000-05-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
9
Fiscal Year
2009
Total Cost
$511,570
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Thibeault, Susan L; Welham, Nathan V (2017) Strategies for advancing laryngeal tissue engineering. Laryngoscope 127:2319-2320
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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
Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho et al. (2016) Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model. Clin Exp Otorhinolaryngol 9:56-61
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
Tateya, Ichiro; Tateya, Tomoko; Watanuki, Makoto et al. (2015) Homeostasis of hyaluronic acid in normal and scarred vocal folds. J Voice 29:133-9

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