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 HO 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 HO into O. 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.