Nucleoside-modified PVA hydrogel with antibacterial and wet-adhesion properties accelerates healing of diabetic oral ulcers.

Oral ulcers, particularly in diabetic patients, pose significant clinical challenges due to impaired healing conditions and high susceptibility to infection. Considering the highly dynamic, moist, and complex multi-bacterial environment of the oral cavity, there is an urgent need to develop a bioactive formulation with wet-adhesion and antibacterial properties to manage diabetic oral ulcers. Here, we developed a novel multifunctional hydrogel (polyvinyl alcohol-borate-cytidine-Ag+, PBCA) based on the i-motif structure of C-Ag+-C coordination, boronate ester bonds formed between PVA and cytidine, and glucocorticoid loading. The hydrogel exhibited excellent physicochemical properties, with an adhesion force of up to 46.6 ± 2.1 kPa. It can adhere to the oral mucosa of rats for over one hour and features continuous silver ion release and structural stability. In vitro studies confirmed its broad-spectrum antibacterial efficacy against both bacterial and fungal oral pathogens, alongside outstanding cytocompatibility with human oral keratinocytes and mouse fibroblasts. In vivo experiments using an oral ulcer model in diabetic rats demonstrated that PBCA hydrogel significantly accelerated mucosal healing, enhanced collagen deposition, promoted angiogenesis, and reduced local inflammation without inducing systemic organ toxicity or skin and oral mucosa irritation. These findings suggest that PBCA hydrogel provides a promising material-based strategy for the treatment of complex chronic oral ulcers under impaired healing conditions.