Multifunctional Hydrogel with Dual Functions of ROS Scavenging and Responsive Antibiotic Release for Synergistic Oral Mucositis Treatment

Radiotherapy- and chemotherapy-induced oral mucositis (OM), characterized by high incidence and delayed healing, significantly impacts patient recovery and quality of life. Current clinical management of OM wounds remains unsatisfactory, primarily due to the risks of oxidative damage and bacterial infection during the healing process. To address this challenge, we developed a multifunctional hydrogel (QTMP-Gel) based on dynamic cross-linking between quaternary ammonium chitosan (QCS) and tannic acid (TA). This QCS-TA matrix provides robust adhesion to wet oral mucosa and enables ROS-responsive drug release. The hydrogel is coloaded with two active components: platinum nanoparticles, which exhibit catalase-like activity for efficient and sustained ROS scavenging, and the broad-spectrum antibiotic minocycline hydrochloride, which provides synergistic antibacterial and anti-inflammatory effects. In vitro assays demonstrated excellent biocompatibility, remarkable antioxidant capacity, and effective inhibition of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. In an acetic acid-induced hamster oral mucositis model, QTMP-Gel significantly accelerated wound healing, markedly downregulated the expression levels of key proinflammatory cytokines, and efficiently cleared local excess ROS, thereby achieving comprehensive therapy through pathological mechanism intervention and infection control. This study provides a promising strategy and offers novel insights into developing intelligent, multisynergistic therapeutics for oral mucositis.