Recent Advances in Microenvironment-Responsive Materials for Periodontitis Therapy.

Periodontitis is a chronic inflammatory condition characterized by the progressive destruction of periodontal supporting tissues. With a global prevalence exceeding 60%, it poses a significant public health challenge. Traditional therapeutic approaches, primarily mechanical debridement, systemic antibiotics, and surgical interventions, often face limitations such as incomplete biofilm removal, rapid drug clearance, and systemic adverse effects. To overcome these challenges, recent research has shifted towards the development of intelligent biomaterials capable of modulating the pathological microenvironment. These microenvironment-responsive strategies leverage unique biochemical signatures, including acidic pH, elevated reactive oxygen species (ROS), and enzymatic dysregulation, to facilitate precise, on-demand drug delivery at the lesion site. This review examines recent advances from three integrated perspectives: (1) material platforms (hydrogels, microneedles, fiber membranes, microspheres, inorganic nanoparticles, and vesicles); (2) responsive design (pH, ROS, enzyme, glucose, and multi-stimulus cascade logic); and (3) spatiotemporal functional orchestration (early-stage microecological remodeling, mid-stage osteoimmunomodulation, and late-stage tissue regeneration). Additionally, we analyze critical translational challenges, including manufacturing scalability, clinical sterilization, and long-term biosafety, while discussing prospects for clinical implementation. This review aims to provide a strategic roadmap and theoretical guidance for the development of next-generation precision therapies for periodontitis.