Vocal fold scarring is a debilitation condition that has proven difficult to treat with current surgical techniques or standard injectable fillers. Our long term aim is to engineer injectable products that promote wound repair and induce tissue regeneration to treat chronic vocal fold scarring and other extracellular matrix (ECM) defects of the lamina propria. This proposal aims to harness the capacity of implanted materials to modulate the phenotype of invading macrophages and vocal fold fibroblasts toward achieving improved restoration of chronic vocal fold scar. We will develop PEGDA based injectable hydrogels that will be conjugated to cytokines previously identified as anti-fibrotic and/or immunomodulatory. Our working hypothesis is that these PEGDA cytokine hydrogels will be able to shift myofibroblasts found in chronic scar toward a normal vocal fold fibroblast phenotype associated with normal vocal fold lamina propria structure and function. We further hypothesize that the classically activated phenotype that is undesirable for chronic vocal fold scar restoration will be modified to an anti-inflammatory phenotype in the presence of our developed hydrogels. We will employ a unique combination of systematic chemical, in vitro cell 2D/3D mono/co culture studies, in vivo and ex vivo studies to resolve the complex interactions among cell biomaterial characteristics, and influences on cell behavior, biomechanics and the surgical requisites necessary to create a suitable clinical outcome. Our findings will provide the necessary ground work for manipulating chronic vocal fold scar phenotypes as a mechanism to promote rapid, complete restoration of vocal fold function.

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. This approach focuses on developing biomaterials that will alter macrophage and myofibroblast phenotypes as an innovative and fundamental biological approach to improving vocal fold scarring.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Schools of Medicine
United States
Zip Code
Erndt-Marino, Josh D; Jimenez-Vergara, Andrea C; Diaz-Rodriguez, Patricia et al. (2018) In vitro evaluation of a basic fibroblast growth factor-containing hydrogel toward vocal fold lamina propria scar treatment. J Biomed Mater Res B Appl Biomater 106:1258-1267
Samavedi, Satyavrata; Diaz-Rodriguez, Patricia; Erndt-Marino, Joshua D et al. (2017) A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis. Tissue Eng Part A 23:101-114
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
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
Branco, Anete; Bartley, Stephanie M; King, Suzanne N et al. (2016) Vocal fold myofibroblast profile of scarring. Laryngoscope 126:E110-7
King, Suzanne N; Guille, Jeremy; Thibeault, Susan L (2015) Characterization of the Leukocyte Response in Acute Vocal Fold Injury. PLoS One 10:e0139260
Hughes, Lindsay A; Gaston, Joel; McAlindon, Katherine et al. (2015) Electrospun fiber constructs for vocal fold tissue engineering: effects of alignment and elastomeric polypeptide coating. Acta Biomater 13:111-20