Highlights
• Wound healing necessitates dynamic glucose metabolism shifts: glycolysis fuels early migration; oxidative phosphorylation drives later matrix synthesis. Chronic wounds exhibit metabolic dysfunction, suggesting “spatiotemporal regulation” as a therapy.
• Macrophage polarization (M1/M2) and glucose metabolism are interconnected. AMPK/STAT6 dysregulation in diabetic wounds impairs immune homeostasis, addressable via metabolic reprogramming.
• Enzymes (HK2/PFKFB3) and metabolites (lactate) exhibit dual therapeutic roles, promoting repair but potentially causing scar hyperplasia/inhibiting MMPs. Stage-specific interventions (e.g. PFKFB3 inhibition) and nanodelivery systems hold promise.
• Diabetic wounds display mitochondrial dysfunction (imbalanced dynamics, ROS), hindering healing. Mitochondrial transplantation or antioxidants (SkQ1) can restore metabolism and promote repair.
• Multi-pathway synergistic interventions, including traditional medicine and responsive materials, offer a comprehensive metabolic-immune-microenvironment approach for diabetic foot ulcers.
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