Abstract

Existing methods for treating diabetic oral ulcers often fall short in clinical environments due to potential bacterial contamination, oxidative harm, and hindered angiogenesis throughout the healing process. Here, a hydrogel patch (HYG2) have been developed for local in situ application. HYG2 comprises oxidized pullulan, quaternized chitosan, and eumelanin nanoparticles derived from cuttlefish ink. These components work together to efficiently heal wounds associated with diabetic oral ulcers. Application begins with a simple local injection that quickly forms a protective barrier over the mucosa, effectively stopping bleeding and counteracting inflammatory agents. HYG2 is distinguished by its strong antibacterial properties and capacity to eliminate reactive oxygen species, promoting bacteria clearance and managing oxidative stress, which accelerates the healing phase from inflammation to tissue regeneration. Additionally, HYG2's 3D structure, incorporating elements from natural sources, offers exemplary support for structural and nutritional cell needs. This enhancement fosters cell adhesion, migration, and proliferation, along with further angiogenesis during mucosal remodeling. Ultimately, HYG2 is fully absorbed by the body after serving its therapeutic functions. Evidence from in vitro and in vivo studies shows that HYG2 hydrogel markedly accelerates mucosal wound repair, making it a promising treatment for diabetic oral ulcers.