Oxygen generating magnesium peroxide nanoparticles by in-situ catalytic reaction with nano‑manganese oxide promote rapid healing of chronic diabetic wounds.

Wound healing is a natural physiological reaction to tissue damage/injury, which involves a complex process between various cells, cytokines, and the vascular system. Chronic diabetic wounds take several weeks to months to heal due to persistent hypoxia and elevated inflammation. Herein, we developed a nanococktail of magnesium peroxide and manganese oxide (MgO2 + MnO2) to promote in-situ catalytic generation of therapeutic levels of oxygen (O2) for rapid wound-healing in mouse models. In vitro studies showed the ability to reduce reactive oxygen species (ROS) following the treatment of the nanococktail. They were biocompatible in vitro and in vivo in the chicken embryonic model at a therapeutic dose. The controlled oxygen generation from MgO2 by the in-situ nanocatalysis using MnO2 was utilized to promote rapid wound healing within 7 days in a normal wound model in the BALB/C and 11 days in a chronic diabetic wound model in the C57BL/6 mouse. In conclusion, our study demonstrated a synergistic MgO2 + MnO2 nanococktail design that provides unique advantages over single-component systems by achieving both functional and mechanistic novelty through a dual-stage oxygen generation process. Importantly, the MgO2 + MnO2 nanococktail exhibited significantly higher and sustained oxygen release compared to the widely studied conventional peroxidase system, thereby providing a superior therapeutic benefit for promoting tissue regenerating application in diabetic conditions.