Sonodynamic therapy for chronic wound healing: Cavitation-mediated ROS chemistry, hypoxia tolerance, and ultrasound-responsive platforms

Objectives Chronic wounds are difficult to treat because infection, biofilm formation, persistent inflammation, inadequate perfusion, hypoxia, and redox imbalance often coexist and reinforce one another. This review discusses sonodynamic therapy (SDT), an ultrasound-activated approach for chronic wounds, with a focus on cavitation-mediated reactive oxygen species (ROS) chemistry, hypoxia tolerance, antibacterial and antibiofilm effects, and ultrasound-responsive biomaterials. Methods We searched PubMed, Web of Science, Google Scholar, and ScienceDirect, with an emphasis on studies published from January 2019 to August 2026. Priority was given to wound-specific and in vivo studies. Earlier foundational publications and selected non-wound studies were included when needed to provide insight into mechanisms that remain insufficiently explored in chronic-wound SDT. Results Current evidence suggests that SDT involves multiple chemical and mechanical processes rather than a single ROS-generating mechanism. Depending on acoustic and material conditions, acoustic cavitation, water sonolysis, sonoluminescence-assisted sensitizer activation, sonocatalytic charge separation, piezoelectric polarization, and hotspot-driven radical formation may all contribute. Because these pathways differ in oxygen dependence, partial radical formation may persist in oxygen-limited regions, although SDT should not be considered oxygen-independent. Nanoparticles, hydrogels, piezoelectric materials, and multifunctional dressings have been developed to improve local retention, biofilm access, radical localization, and repeated activation. Much of the evidence remains preclinical, and direct pathway-level support for immunoregulatory, angiogenic, and regenerative effects remains limited. No peer-reviewed human clinical study specifically evaluating SDT for chronic wounds was identified through August 2026. Conclusions SDT should be viewed as a potential adjunct to standard wound care rather than a replacement. Translation will require consistent acoustic reporting, improved characterization of cavitation and ROS, careful assessment of host-tissue safety, practical material design, and clinically meaningful wound endpoints.