Recent advances in natural macromolecule-based hydrogels for treating oral soft tissue inflammation: A review

Oral soft tissue inflammatory diseases (e.g., recurrent aphthous stomatitis, periodontitis, oral mucositis) present persistent clinical challenges due to high prevalence, recurrence, and limited treatment efficacy. Conventional therapies are often limited by rapid clearance, poor retention at the affected site, and systemic side effects. Natural macromolecule-based hydrogels, including chitosan, hyaluronic acid, and gelatin, provide a promising alternative due to their biocompatibility, ability to adhere to mucosal surfaces, and controllable drug release properties. This review summarizes the design strategies and key physicochemical properties of natural macromolecule-based hydrogels and systematically introduces various crosslinking methods, including physical, chemical, and dual-network approaches. It also highlights advanced hydrogel systems responsive to physiological stimuli such as pH, reactive oxygen species, enzymes, or temperature. Furthermore, the review discusses the applications of these hydrogels in common oral soft tissue inflammatory diseases, showing that they not only accelerate tissue repair but also exert anti-inflammatory, antibacterial, and antioxidant effects through the intrinsic bioactivity of the polymers and controlled drug release. Despite these advances, challenges remain in standardization, large-scale production, and clinical translation. Future research should focus on developing multi-stimuli-responsive platforms, personalized hydrogel systems, and integration with biosensors to enable intelligent therapy. Overall, natural macromolecule-based hydrogels hold significant potential to transform the treatment of oral inflammatory diseases.