Theranostic peptide-selenium hydrogel targeting NETs-mitochondrial dysfunction-pyroptosis axis for chronic diabetic wound repair.

Chronic diabetic wounds are characterized by persistent inflammation, elevated oxidative stress, and impaired angiogenesis. However, effective strategies that simultaneously elucidate the underlying mechanisms and enable precise interventions remain scarce. This study aims to identify the neutrophil extracellular traps (NETs)-mitochondrial dysfunction-pyroptosis pathway as a key driver of impaired angiogenesis in diabetic wounds and to construct an intelligent composite hydrogel with pH-responsiveness and monitoring functions. The system utilizes a pH-responsive oxidized astragalus polysaccharide-gelatin hydrogel matrix that loads and enables the on-demand release of composite particles containing selenium and the antimicrobial peptide Andersonin-W1. These particles inhibit NETs formation, improve mitochondrial function, and reduce pyroptosis. Additionally, the system incorporates pH-responsive fluorescent carbon dots for visual monitoring of the wound microenvironment. In vitro and in vivo experiments demonstrate that the composite hydrogel effectively modulates the pathological axis, accelerates diabetic wound healing, and simultaneously enables visualization of the wound microenvironment. Overall, by integrating clinical single-cell transcriptomic analyses with in vitro and in vivo experiments, this study elucidates the critical role of the NETs-mitochondrial dysfunction-pyroptosis axis in diabetic nonhealing wounds and proposes an integrated platform for visual surveillance and precision treatment.