Pathological Microenvironment-Guided Smart Hydrogels for Periodontitis Therapy

Periodontitis is a chronic inflammatory disease initiated by dental plaque biofilms and mediated by dysregulated host immune responses, frequently resulting in irreversible alveolar bone resorption. Although mechanical debridement, local drug delivery, and antimicrobial therapies are widely applied in clinical practice, their therapeutic efficacy remains limited by insufficient drug retention, nonspecific drug release, antibiotic resistance, and inadequate periodontal tissue regeneration. Recently, smart hydrogels have emerged as promising platforms for periodontal therapy owing to their ECM-mimicking three-dimensional networks, excellent biocompatibility, and ability to respond to specific stimulus signals. Therefore, this review focuses on design strategies for smart hydrogels driven by the periodontal pathological microenvironment, guiding the development of hydrogels responsive to both endogenous and exogenous stimuli. Subsequently, it elaborates on the role of these smart hydrogels in antibacterial, anti-inflammatory, immunomodulatory, and tissue regeneration therapies. Additionally, it explores the challenges faced by smart hydrogels during clinical translation. By integrating disease mechanisms, material design principles, and therapeutic function regulation, this review aims to provide guidance for the development of smart hydrogel systems for periodontal therapy.