Wet-Adhesive Hydrogel Patch for Sustained Oral Ulcer Treatment

Oral ulcers are a common mucosal disorder that causes persistent pain and significantly impairs quality of life for patients. Current therapeutic approaches, including sprays and commercial patches, provide only temporary relief, as the complex, dynamic, and moist oral environment hinders prolonged retention and drug efficacy. Here, we report the rational design of a multifunctional hydrogel adhesive that integrates poly(acrylic acid) (PAA) for hydrogen bonding, polyamidoamine-epichlorohydrin (PAE) for electrostatic interactions with mucosal surfaces, and poly(methyl methacrylate) (PMMA) for swelling resistance. The resulting hydrogel exhibits an instant wet tissue adhesion strength of ∼40 kPa and enhances adhesion after prolonged immersion in phosphate-buffered saline (PBS). Remarkably, it retains high adhesion strength under extreme conditions, such as hypertonic and strongly acidic environments. When loaded with dexamethasone acetate, the hydrogel enables controlled drug release, significantly improving therapeutic outcomes in a rat oral ulcer model. By ensuring prolonged retention and effective drug delivery, this hydrogel patch offers a promising strategy for enhancing oral ulcer treatment.