Sonodynamic Therapy in Periodontitis: From Mechanisms to Biomaterial-Based Innovations

Periodontitis is a common chronic inflammatory disease driven by pathogenic biofilms, leading to progressive periodontal tissue destruction and systemic health risks. Conventional therapies often fail to eradicate biofilms in deep periodontal pockets, promote antimicrobial resistance and offer limited regenerative potential. Although SDT has emerged as a promising alternative, its clinical efficacy is constrained by several material- and microenvironment-related barriers that have not been systematically addressed in previous reviews. Sonodynamic therapy (SDT) employs low-intensity ultrasound to activate sonosensitizers, generating reactive oxygen species (ROS) and inducing mechanical disruption of biofilms, with advantages of deep tissue penetration, broad-spectrum antimicrobial activity and low risk of resistance. Nevertheless, conventional sonosensitizers often exhibit poor water solubility, rapid clearance, limited specificity, and suboptimal ROS generation, while hypoxia, continuous fluid turnover, and mechanical disturbance within periodontal pockets further compromise local retention and therapeutic efficacy. Advances in biomaterials address these barriers by engineering high-performance sonosensitizers to enhance ROS efficiency, developing delivery systems to improve solubility and prolonged retention and integrating multimodal antibacterial and regenerative functions. This review summarizes the mechanistic basis of SDT with recent advances in sonosensitizer engineering, local delivery platforms, synergistic therapies, and multifunctional biomaterials, thereby linking antimicrobial performance to periodontal tissue regeneration. We further identify hypoxia, delivery efficiency, biosafety and the lack of standardized evaluation as key translational challenges, and propose future directions including AI-guided sonosensitizer design, precision delivery systems, and CRISPR-assisted antimicrobial combination strategies to accelerate the clinical translation of SDT for periodontitis management.