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

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004336-13
Application #
8134378
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (03))
Program Officer
Shekim, Lana O
Project Start
2000-02-01
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
13
Fiscal Year
2011
Total Cost
$555,204
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
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
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
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
Chen, Xia; Thibeault, Susan L (2016) Cell-cell interaction between vocal fold fibroblasts and bone marrow mesenchymal stromal cells in three-dimensional hyaluronan hydrogel. J Tissue Eng Regen Med 10:437-46
Stevens, Kimberly A; Thomson, Scott L; Jetté, Marie E et al. (2016) Quantification of Porcine Vocal Fold Geometry. J Voice 30:416-26
Bartlett, R S; Guille, J T; Chen, X et al. (2016) Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment. Cytotherapy 18:1284-96
Li, Linqing; Stiadle, Jeanna M; Lau, Hang K et al. (2016) Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration. Biomaterials 108:91-110
Woo, Joo Hyun; King, Suzanne N; Hoffman, Henry et al. (2016) MERS versus Standard Surgical Approaches for Porcine Vocal Fold Scarring with Adipose Stem Cell Constructs. Otolaryngol Head Neck Surg 155:612-23
Lungova, Vlasta; Leydon, Ciara; Thibeault, Susan (2016) Derivation of Epithelial Cells from Human Embryonic Stem Cells as an In Vitro Model of Vocal Mucosa. Methods Mol Biol 1307:237-43
Branco, Anete; Bartley, Stephanie M; King, Suzanne N et al. (2016) Vocal fold myofibroblast profile of scarring. Laryngoscope 126:E110-7

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