Fabrication of carboxymethylcellulose hydrogel containing β-cyclodextrin–eugenol inclusion complexes for promoting diabetic wound healing

The difficult healing of wounds caused by diabetes remains a challenging clinical problem. The activation of nuclear factor kappa-B as a key factor contributes to prolonged inflammation and inhibition of angiogenesis. As a natural antioxidant, eugenol may downregulate the lectin-like oxidized low-density lipoprotein receptor-1 and inhibit the activation of nuclear factor kappa-B in endothelial cells. However, eugenol shows poor solubility, pungent odor, and volatility, thus impeding its clinical application as a potential therapeutic agent. This study developed a novel bioactive carboxymethylcellulose hydrogel loaded with inclusion complexes of eugenol with β-cyclodextrin (eugenol–β-cyclodextrin/carboxymethylcellulose hydrogel) to regulate lectin-like oxidized low-density lipoprotein receptor-1-induced activation of nuclear factor kappa-B to enhance angiogenesis and inhibit inflammation for accelerating diabetic wound healing in vivo. It was found that eugenol–β-cyclodextrin/carboxymethylcellulose hydrogel exhibited remarkable antibacterial activity in vivo and in vitro. Furthermore, it accelerated diabetic wound healing by reducing the lectin-like oxidized low-density lipoprotein receptor-1/nuclear factor kappa-B-induced dysfunction in endothelial cells and promoting angiogenesis.