Scarless Healing of Injured Vocal Folds Using an Injectable Hyaluronic Acid-Waterborne Polyurethane Hybrid Hydrogel to Tune Inflammation and Collagen Deposition

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.