In situ encapsulation of Cu-MOF in wax gourd sponge for integrated smart treatment of diabetic wounds

Diabetic wounds, recognized as one of the most severe complications of diabetes, frequently experience delayed healing owing to factors such as infection, persistent inflammation, impaired angiogenesis, and cellular dysfunction. Therefore, intelligent dressings that can dynamically respond to the wound microenvironment and integrate multiple therapeutic functions are urgently required. In this study, we developed a decellularized winter melon sponge material integrated with a Cu/Zn bimetallic ZIF-8 metal–organic framework (Cu-MOF), termed P 1 W 1 @Cu-MOF. This innovative material was synthesized by crosslinking decellularized winter-melon powder with a porcine decellularized dermal matrix to form a three-dimensional porous sponge. Employing an in situ synthesis strategy, we effectively loaded Cu-MOF into the sponge, conferring pH-responsive drug release properties. In vitro studies demonstrated that P 1 W 1 @Cu-MOF rapidly released Cu 2 ⁺/Zn 2 ⁺ in an acidic environment mimicking diabetic wounds (pH = 5.4), exhibiting over 94% antibacterial activity. Additionally, P 1 W 1 @Cu-MOF significantly promoted endothelial cell tube formation and facilitated the polarization of macrophages towards the M2 reparative phenotype. Animal experiments have revealed that this material markedly accelerates healing of infected wounds in diabetic rats. Mechanistic studies indicated that P 1 W 1 @Cu-MOF activated the PI3K/Akt and HIF-1/VEGF signaling pathways to enhance angiogenesis and cell proliferation, while simultaneously inhibiting the NF-κB and TGF-β1/Smad3 pathways, thus alleviating inflammation and mitigating scar formation. This study introduces a novel strategy for intelligent regulation and efficient repair of diabetic wounds through synergistic functionalities, including antibacterial, anti-inflammatory, pro-angiogenic, and anti-scarring effects, highlighting its significant potential for clinical translation. A biomimetic, intelligent dressing (P 1 W 1 @Cu‑MOF) was fabricated by crosslinking decellularized winter‑melon powder with a porcine decellularized dermal matrix to form a 3D porous sponge, followed by in situ growth of a Cu/Zn bimetallic ZIF‑8 MOF. In the acidic diabetic-wound microenvironment (pH 5.4), the sponge enables pH‑responsive release of Cu²⁺/Zn²⁺, providing potent antibacterial activity (>94%) while simultaneously promoting endothelial tube formation and driving macrophage polarization toward the M2 reparative phenotype. In infected diabetic rat wounds, P 1 W 1 @Cu‑MOF accelerates closure and tissue regeneration by activating PI3K/Akt and Hif‑1/VEGF pathways to enhance angiogenesis/proliferation and suppressing NF‑κB and TGF‑β1/Smad3 signaling to reduce inflammation and scarring, demonstrating a synergistic antibacterial, anti‑inflammatory, pro‑angiogenic, and anti‑scarring strategy with strong translational potential.