Tunicate-Inspired Carboxymethyl Cellulose Hydrogel Filler for Treating Age-Associated Vocal Fold Atrophy

For the treatment of dysphonia and aspiration induced by presbylaryngis, injection laryngoplasty is widely conducted. Here, the feasibility of carboxymethyl cellulose hydrogel modified with pyrogallol (CMC-PG) is checked for injection laryngoplasty. CMC-PG, owing to its low viscosity, is easily injectable in liquid form and can self-polymerize into a hydrogel without the need for oxidative cross-linking agents. Moreover, the CMC-PG hydrogel demonstrates improved stability, tissue adhesiveness, and elastic modulus, compared to a commercial product currently being used for injection laryngoplasty. CMC-PG hydrogel has high binding affinity to various functional moieties and can maintain its structure under swelling condition for an extended period, thereby enabling sustained release of growth factors. CMC-PG is highly biocompatible both in vitro and in vivo, and it does not induce fibrosis or immunogenic responses. Injection of CMC-PG hydrogel encapsulating basic fibroblast growth factor (bFGF) regenerates both the lamina propria and the muscle layer in the vocal folds of an aged rat model, showing increased hyaluronic acids layer and muscle density, enhanced angiogenesis, and modulated immunogenicity. Importantly, bFGF-loaded CMC-PG hydrogel facilitates functional restoration of the aged vocal folds. This study offers clinical potential of CMC-PG hydrogel for injection laryngoplasty for the treatment of presbylaryngis.