A pH-Sensitive and mitochondria-modulating intelligent multilayered dressing system for a comprehensive therapeutic strategy of diabetic wounds

Diabetic wounds management remains a significant global challenge due to impaired wounds healing, bleeding, and infection. Oxidative stress (OS), resulting from dysregulated mitochondrial reactive oxygen species (mtROS), plays a crucial role in the diabetic wounds pathogenesis. Furthermore, diabetic infected wounds can induce excessive ROS production and an acidic microenvironment due to the accumulation of bacterial metabolic products. Thus, a pH-sensitive intelligent dressing could serve as an ideal carrier for precise regulation of mtROS and promote faster diabetic wounds healing. In this study, we fabricated a pH-sensitive and mitochondria-modulating intelligent multilayered dressing system. We synthesized mesoporous silica-coated selenium particles (SS) for mtROS regulation and infection resistance. These SS were then loaded into a polyvinyl alcohol (PVA)/(N-[(2-hydroxy-3-trimethylamine) propyl] chitosan chloride, HTCC) hydrogel for pH-sensitive controlled release, blood coagulation, and antibacterial treatment. Finally, the resulting system was cross-linked with carboxymethyl cotton gauze (CG) to enhance hemostatic ability and reduce adhesiveness. Experimental results from cellular and animal models of diabetic wounds demonstrated that HTCC/PVA/SS-CG dressing promotes faster hemostasis, protects against microbial infection, and accelerates diabetic wounds healing through its mitochondria-modulating action, which offers a comprehensive treatment strategy for diabetic wounds and shows promising prospects for clinical transformation.