Metal organic framework based synergistic improvement of hypoxia for optimizing diabetic wounds healing

In the physiological process of wound healing, an appropriate level of inflammation is conducive to the clearance of necrotic tissue and cells. However, due to insufficient blood supply and a high-glucose microenvironment, diabetic wounds have long been in a state of severe hypoxia and inflammation, which seriously hampers their transition to the proliferative stage. This study puts forward a strategy to synergistically ameliorate hypoxia based on ZnO₂/CeO₂@ZIF-8 (ZCZ). Specifically, ZnO₂ generates exogenous O₂ upon reacting with H₂O, while CeO₂ converts endogenous reactive oxygen species (ROS) into O₂. During the early-stage repair processes, ZCZ can promote the proliferation, migration, and tubular formation of vascular endothelial cells, as well as neovascularization. Through an in vivo diabetic wound model, it was observed that ZCZ significantly reduced the wound healing time. It also enhanced the dermal thickness by increasing collagen deposition, along with elevating the presence of M2 macrophages, augmenting neovascularization, and improving the oxygen-carrying capacity. Mechanism studies have indicated that ZCZ mainly exerts its effects through inhibiting the IL6/JAK2/STAT3 pathway. Consequently, the proposed strategy not only offers a novel clinical option but also paves a new path for the management of chronic and recalcitrant wounds.