Advances in the application of novel smart hydrogels for periodontal tissue regeneration

Periodontal disease is a persistent inflammatory condition caused by pathogenic microorganisms, primarily characterized by the progressive destruction of the tooth-supporting structures (namely, the periodontal ligament, cementum, and alveolar bone) as well as the associated gingival tissues. Hydrogel matrices, distinguished by their superior cytocompatibility profiles, are increasingly recognized as viable therapeutic scaffolds for orchestrating periodontal tissue repair and functional restoration. This review outlines the fundamental requirements for hydrogel-based periodontal regeneration and highlights recent advances in smart, stimuli-responsive hydrogels responsive to endogenous stimuli (reactive oxygen species (ROS), matrix metalloproteinases (MMPs)) and exogenous stimuli (temperature, light, electric fields, pH). We describe innovative fabrication strategies, underlying responsive mechanisms, and associated molecular signaling pathways. Furthermore, we critically review probiotic-hydrogel composites that modulate oral microbiota homeostasis to construct immune microenvironments favorable for bone regeneration, as well as metal-organic framework (MOF)-based hydrogels achieving multifunctional therapeutic effects including antimicrobial, antioxidant, and osteogenic activities through sustained metal ion release. This review presents diverse design strategies for developing novel intelligent functional materials and establishes a theoretical foundation for precision therapeutic approaches against periodontitis.