Smart Nanogel Systems for Periodontitis Management: A Review of Microenvironment-Targeted Therapies.

Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis and characterized by an exaggerated host immune response, leading to progressive and irreversible alveolar bone resorption. Current therapies, such as mechanical debridement and antibiotics, are empirical and fail to address the dynamic pathological microenvironment, resulting in incomplete pathogen eradication and poor tissue regeneration. Recent advances in nanotechnology have enabled the development of nanogel-based systems that intelligently adapt to key microenvironmental features, including pH fluctuations, reactive oxygen species (ROS), matrix metalloproteinases (MMPs), and microbial biofilms, enabling on-demand drug release, synergistic antibacterial effects, and enhanced regeneration. This review aims to provide a comprehensive and critical overview of responsive nanogels for precise periodontitis treatment. Based on a systematic analysis of the literature published in recent years, the material basis and design principles of nanogels are comprehensively summarized, with emphasis on innovative strategies for periodontal microgels, and the mechanisms of regulation of infection, inflammation and tissue remodeling are discussed. Special emphasis is placed on recent advances in multifunctional nanogel systems that enable more precise and controlled therapeutic interventions. In addition, this review critically discusses the advantages and limitations of different response strategies and outlines key challenges related to biosafety, reproducibility, scalability, and clinical transition. Overall, responsive nanogels represent a promising platform for improving efficacy and specificity of periodontal treatments, although further efforts are needed to facilitate their translation into clinical applications.