Engineering anti-inflammatory magnesium-mangiferin hydrogel for diabetic wound healing

• Self-assembled Mg 2+ -mangiferin hydrogel forms via H-bonding, metal chelation, and π-π stacking without carriers or modification. • Dual ROS scavenging and M2 macrophage polarization via JAK2/STAT3/NF-κB modulation resolve inflammatory microenvironment. • VEGF-driven angiogenesis and rapid hemostasis synergistically accelerate diabetic wound closure. • Injectable hydrogel achieves almost 100% epithelialization in diabetic rats within two weeks, performing the potential as a novel wound dressing material. Excessive inflammation and impaired vascularization are hallmark features of diabetic wounds, contributing significantly to the failure of the wound healing process. Hence, effective therapies must simultaneously dampen inflammation and restore angiogenesis. Current wound dressings often involve intricate fabrication processes and rely on costly interventions like cytokine delivery and cell-based treatments. Significant attention has been directed toward the self-assembly of bioactive herbal compounds into functional hydrogels without structural alteration for biological purposes. Here, we developed a magnesium-mangiferin hydrogel (MMG) to improve diabetic wound repair. The MMG hydrogel self-assembled via hydrogen bonding, π-π stacking, and metal chelation, without the need for additional carriers or structural modifications, and it exhibited excellent moldability, injectability, and biocompatibility. Through regulation of oxidative stress and macrophage polarization toward the M2 phenotype, along with modulation of NF-κB and JAK2/STAT3 pathways, it enhanced inflammatory phase resolution in diabetic wounds. Meanwhile, it stimulated elevated VEGF expression, driving angiogenesis and accelerating the proliferative and remodeling phases, which ultimately enhanced wound healing. Furthermore, MMG demonstrated excellent hemostatic properties. Overall, MMG demonstrated significant efficacy in treating diabetic wounds, highlighting its potential as a novel wound dressing material.