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.
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.
|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|