Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo_4/3B_2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo_4/3B_2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo_4/3B_2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo_4/3B_2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo_4/3B_2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo_4/3B_2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms. © 2024 American Chemical Society