Normal vocal fold vibration is crucially dependent upon tissue composition and viscoelasticity. When composition of the extracellular matrix (ECM) of the vocal fold cover (i.e. lamina propria - superficial and middle layers) is altered, vocal fold vibratory function can be severely disrupted due to alterations in tissue viscoelasticity. The dysphonias that result are generally difficult to treat effectively with current surgical paradigms and available biomaterials. Treatment failures have been ascribed to poor understanding of pathologic processes in the ECM, as well as suboptimal materials that may negatively affect vocal fold biomechanical properties. Accordingly, there is a clinical need for improved understanding of the pathophysiology of disrupted ECM and the development of advanced biomaterials that appreciate the biomechanical properties of the lamina propria. The long-term aim of this project is to engineer injectable products that promote wound repair and induce tissue regeneration, for treatment of scarring and other existing ECM defects of the lamina propria, exclusively for the superficial and middle layers. For the proposed funding period, we will specifically focus on chemically modified injectable synthetic ECM (sECM) hydrogels (HA derivatives) for tissue regeneration. These products will mimic and augment the existing ECM and yield optimal vocal fold ECM biomechanical properties. We will employ a unique combination of systematic chemical, biomechanical, in vitro and in vivo studies to resolve the complex interactions among cell and biomaterial characteristics, biomechanical properties and influences on cell behavior and the surgical requisites necessary to create a suitable clinical outcome. The overarching hypothesis is that manipulation of the ECM with injectable HA hydrogels and sols that have been encapsulated with living cells will yield optimal tissue composition and biomechanically optimal results.

Public Health Relevance

Voice disorders affect an estimated 3-9% of Americans yearly and 29% of the population in their lifetime. Treatment for vocal fold scarring, a voice disorder caused by connective tissue or ECM injury or loss has been limited. The proposed research defines a novel and fundamental tissue engineering approach to repair vocal folds with longstanding damage due to injury or disease PROJECT NARRATIVE Voice disorders affect an estimated 3-9% of Americans yearly and 29% of the population in their lifetime. Treatment for vocal fold scarring, a voice disorder caused by connective tissue or ECM injury or loss has been limited. The proposed research defines a novel and fundamental tissue engineering approach to repair vocal folds with longstanding damage due to injury or disease

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004336-16
Application #
8704322
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Shekim, Lana O
Project Start
2000-02-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
Bartlett, Rebecca S; Gaston, Joel D; Ye, Shuyun et al. (2018) Mechanotransduction of vocal fold fibroblasts and mesenchymal stromal cells in the context of the vocal fold mechanome. J Biomech :
Li, Linqing; Stiadle, Jeanna M; Levendoski, Elizabeth E et al. (2018) Biocompatibility of injectable resilin-based hydrogels. J Biomed Mater Res A 106:2229-2242
Brates, Danielle; Molfenter, Sonja M; Thibeault, Susan L (2018) Assessing Hyolaryngeal Excursion: Comparing Quantitative Methods to Palpation at the Bedside and Visualization During Videofluoroscopy. Dysphagia :
Bartlett, Rebecca S; Thibeault, Susan L (2018) Insights Into Oropharyngeal Dysphagia From Administrative Data and Clinical Registries: A Literature Review. Am J Speech Lang Pathol 27:868-883
Lungova, Vlasta; Verheyden, Jamie M; Sun, Xin et al. (2018) ?-Catenin signaling is essential for mammalian larynx recanalization and the establishment of vocal fold progenitor cells. Development 145:
Chen, Xia; Foote, Alexander G; Thibeault, Susan L (2017) Cell density, dimethylsulfoxide concentration and needle gauge affect hydrogel-induced bone marrow mesenchymal stromal cell viability. Cytotherapy 19:1522-1528
Li-Jessen, Nicole Y K; Powell, Michael; Choi, Ae-Jin et al. (2017) Cellular source and proinflammatory roles of high-mobility group box 1 in surgically injured rat vocal folds. Laryngoscope 127:E193-E200
Thibeault, Susan L; Welham, Nathan V (2017) Strategies for advancing laryngeal tissue engineering. Laryngoscope 127:2319-2320
Tang, Sharon S; Mohad, Vidisha; Gowda, Madhu et al. (2017) Insights Into the Role of Collagen in Vocal Fold Health and Disease. J Voice 31:520-527
Stevens, Kimberly A; Thomson, Scott L; Jetté, Marie E et al. (2016) Quantification of Porcine Vocal Fold Geometry. J Voice 30:416-26

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