Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.

Fracture nonunion can result in considerable physical harm and limitation of quality of life in patients, exerting an extensive economic burden to the society. Nonunion largely results from unresolved inflammation and impaired osteogenesis. Despite advancements in surgical techniques, the indispensable treatment for nonunion is robust anti-inflammation therapy and the promotion of osteogenic differentiation. Herein, we report that plasma exosomes derived from infected fracture nonunion patients (Non-Exos) delayed fracture repair in mice by inhibiting the osteogenic differentiation of bone marrow stromal cells in vivo and in vitro. Unique molecular identifier microRNA-sequencing (UID miRNA-seq) suggested that micro-RNA-708-5p (miR-708-5p) was overexpressed in Non-Exos. Mechanistically, miR-708-5p targeted structure-specific recognition protein 1, thereby suppressing the Wnt/β-catenin signaling pathway, which, in turn, impaired osteogenic differentiation. AntagomicroRNA-708-5p (antagomiR-708-5p) could partly reverse the above process. A bacteria-sensitive natural polymer hyaluronic-acid-based hydrogel (HA hydrogel) loaded with antagomiR-708-5p exhibited promising effects in an in vivo study through antibacterial and pro-osteogenic differentiation functions in infected fractures. Overall, the effectiveness and reliability of an injectable bacteriasensitive hydrogel with sustained release of agents represent a promising approach for infected fractures.