Oxygenous and biofilm-targeted nanosonosensitizer anchored with Pt nanozyme and antimicrobial peptide in the gelatin/sodium alginate hydrogel for infected diabetic wound healing

Sonodynamic therapy is an emerging therapeutic approach for combating bacterial infections. However, the characteristics of hypoxia, high H 2 O 2 microenvironment, and the formation of persistent biofilms in diabetic wound sites limit its efficacy in this field. To address these issues, we developed a multifunctional antibacterial hydrogel dressing PPCN@Pt-AMPs/HGel with the cross-linked gelatin and sodium alginate as the matrix, where the nanosonosensitizer PCN-224 was decorated with the oxygen-generating Pt nanoenzyme and further coupled with a biofilm-targeting antimicrobial peptide via an interacting polydopamine layer. This nano-composite hydrogel displayed improved mechanical properties as well as good biocompatibility and biodegradability. The catalase-like activity of the nanoparticles facilitated the ultrasound-induced generation of the singlet oxygen due to the catalytic decomposition of the H 2 O 2 into O 2 . In vitro results showed that the hydrogel dressing exhibited excellent antimicrobial ability under low-intensity ultrasound stimulation, which could effectively inhibit the newly formed biofilm and eliminate the full-grown biofilms. In the infected diabetic wound of rats, PPCN@Pt-AMPs/HGel significantly enhanced the wound healing rate under low-intensity ultrasound stimulation and improved the regeneration outcomes by promoting granulation tissue formation, angiogenesis, and type III collagen deposition. In conclusion, our study provides a novel and effective antibacterial hydrogel dressing for sonodynamic treatment of diabetic wounds.