RFA-DC-22-001: Translating a biostimulatory implant for the long-term treatment of glottic insufficiency Abstract Glottic insufficiency (GI) is a laryngeal disorder that can impair communication and swallowing function due to vocal fold paralysis, presbylarynges, trauma, surgery, or radiation. The most common treatment for GI is vocal fold augmentation with temporary nanoporous biomaterials that assist with glottic closure. However, currently available materials poorly restore the biomechanical properties of the native vocal fold and can be associated with dense histiocytic responses, while only lasting three to eighteen months. In addition, vocal folds are a complex laminar tissue capable of producing voice due to specific mechanical properties of the extracellular matrix and cellular components. However, the structural, cellular, and intrinsic mechanical effects of vocal fold augmentation have not yet been fully characterized, particularly after achieving homeostasis in situ. There is a need for a well characterized and purposefully-designed injectable implant that can restore permanent laryngeal function without producing inflammation or compromising vocal fold pliability. To address this need, we developed a novel iteration of microporous annealed particle (MAP) scaffold that is biomechanically matched to the vocal fold, capable of promoting tissue integration, and providing persistent tissue bulk. This proposal aims to (1) develop assays of MAP-associated de novo tissue formation, (2) characterize the clinical feasibility of in vivo delivery, (3) determine the toxicology profile and (4) initiate a first-in-human clinical trial of MAP hydrogel vocal fold augmentation.