An ultrasound-switchable hydrogel enables sequential antibacterial and anti-inflammatory therapy for infected diabetic wounds.

Traditional dressings often fail to address the dynamic progression of infected diabetic wounds, which requires early bacterial elimination followed by timely control of oxidative stress and inflammation. Here, we developed an ultrasound-switchable Ce6/celastrol hydrogel for sequential antibacterial and anti-inflammatory therapy. Chlorin e6 (Ce6) and celastrol were co-encapsulated in a gelatin methacrylate (GelMA) hydrogel. Upon ultrasound irradiation, Ce6 generated singlet oxygen to reduce methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) in vitro. After ultrasound cessation, celastrol scavenged residual reactive oxygen species and suppressed inflammation. In an MRSA-infected diabetic wound model, the hydrogel with ultrasound reduced bacterial burden, alleviated inflammation, promoted collagen deposition, and accelerated wound closure. This strategy provides temporally regulated antibacterial and anti-inflammatory therapy for infected diabetic wounds.