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 P1W1@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 P1W1@Cu-MOF rapidly released Cu2⁺/Zn2⁺ in an acidic environment mimicking diabetic wounds (pH = 5.4), exhibiting over 94% antibacterial activity. Additionally, P1W1@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 P1W1@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.