Abstract
Localized drug delivery in the oral cavity is challenging owing to its wet, dynamic, and microbiologically complex nature. Adhesive hydrogels have attracted increasing attention for their ability to adhere under wet conditions, provide sustained drug release, and respond to pathological environments. This review provides a structured perspective by categorizing advancements into a three-level hierarchy encompassing molecular bonding, network reinforcement, and system-level adaptation. Chemical motifs for interfacial stability and responsive designs are systematically evaluated to enhance site-specific compatibility. Unlike previous reports that primarily cataloged material types, this study distinguishes itself through a rigorous quantitative comparison between experimental hydrogels and clinical gold standards across diverse oral pathologies. A primary differentiator is the emphasis on biomechanical crosstalk where microbial enzymatic activity and mechanical fatigue concurrently dictate the longevity of the adhesive interface. Furthermore, the work identifies systemic disconnects in current testing methodologies and advocates for integrated evaluation paradigms that simulate simultaneous physical and biological stressors. By synthesizing these granular insights, this review offers a comprehensive roadmap for achieving stable and efficient therapy in next-generation oral medicine.