Ultrasound-programmable adhesive hydrogel platform for sequential treatment of infected wounds

Chronic infected wounds remain a clinical challenge to treat due to persistent bacterial colonization, heterogeneous healing microenvironments, and antibiotic resistance. Here, we developed an ultrasound-programmable adhesive hydrogel platform that sequentially coordinates tissue adhesion, transdermal nanoparticle delivery, sonodynamic activation, and tissue regeneration within an integrated therapeutic cascade. Amino-functionalized N-doped graphene quantum dots (aN-GQDs)-modified ZIF-8 nanocomposites (ZIF-8@aN-GQDs) were embedded within a polyacrylamide/alginate hydrogel (PA-ZA). Programmed kHz- and MHz-frequency ultrasound enables non-chemical tissue adhesion followed by transdermal delivery of ZIF-8@aN-GQDs with sonodynamic ROS generation for antibacterial activity. PA-ZA exhibited favorable biocompatibility and promoted cell migration and angiogenesis in vitro. In a full-thickness infected skin-defect model, ultrasound-activated PA-ZA reduced bacterial burden, accelerated inflammatory resolution, and induced dynamic regulation of angiogenesis, thereby expediting wound repair. Interestingly, a similar wound-closure benefit was maintained in a subcutaneous infection model, supporting potential use in non-exposed and anatomically constrained deep infections. Overall, this work establishes a programmable therapeutic strategy in which ultrasound governs tissue adhesion and on-demand treatment of complex infected wounds, with potential relevance to infected wounds and other anatomically constrained superficial infections.