Oxidized carbon nanohorns-reinforced dual-responsive hydrogel for internal-external synergistic diabetic wound repair

This study aims to address the challenge of mitochondrial energy metabolism disorders induced by the hyperglycemic microenvironment of diabetic wounds. We developed an intelligent dual-responsive hydrogel and propose an innovative "internal-external synergistic" therapeutic strategy. The dynamic crosslinked network of the hydrogel responds to high glucose and reactive oxygen species (ROS) signals in the wound microenvironment, consuming these pathological factors to achieve external microenvironmental regulation while triggering the precise release of encapsulated oxidized carbon nanohorns (oxCNHs). As a "functional enhancement unit" and "mitochondrial energy restorer", oxCNHs stabilize the hydrogel network through multivalent interactions prior to signal activation, and upon signal stimulation, activate AMPKα via phosphorylation to restore mitochondrial energy metabolism. This metabolic restoration drives the assembly of F-actin stress fibers, which provide the necessary driving force for directed cell migration and angiogenesis. In vivo experiments demonstrated the hydrogel's significant efficacy in promoting wound repair. This study advances the role of oxCNHs from mere passive drug carriers to active metabolic regulators. Furthermore, it introduces an innovative paradigm for diabetic wound healing through a synergistic approach that externally modifies the microenvironment while internally reactivating the cellular energy machinery.