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) 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, both for prophylactic treatment and for existing ECM defects of the lamina propria, i.e., scarring. We will focus on hyaluronic acid (HA) and its derivatives. These products will mimic normal ECM composition and yield optimal vocal fold ECM biomechanical properties. We will accomplish our long-term aim through a unique combination of systematic chemical, biomechanical, in vitro and in vivo animal studies. The overarching hypothesis is that in vivo ECM manipulation with injectable HA agents will yield optimal tissue composition and biomechanically functional results.
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