ROS scavenging Mn3O4 nanozyme regulated immune microenvironment and affects intercellular interaction to promote wound healing in diabetes

Abstract Diabetes-induced chronic wound healing poses significant clinical and economic challenges. In the pathological context of diabetic wounds, the accumulation of reactive oxygen species (ROS) and inflammatory factors is exacerbated, impeding the transition of macrophages from the M1 to M2 phenotype, thereby leading to prolonged wound healing. Therefore, this study has developed an ultra-small tri-manganese tetroxide nanozyme with dual superoxide dismutase/catalase enzymatic activities, which exhibits excellent ROS scavenging performance. Under oxidative stress conditions, this nanozyme can alleviate mitochondrial damage and promote the transition of macrophages from the M1 to M2 phenotype, thereby mitigating the inhibition of cellular function caused by the inflammatory state through intercellular interactions. Furthermore, the application of this nanozyme in vivo has also contributed to the treatment of skin defects in streptozotocin-induced diabetic mice by alleviating inflammation and scavenging ROS. The dual-enzymatic nanozyme designed and prepared in this study, which scavenges ROS, can regulate the local immune microenvironment and intercellular interactions, providing a new strategy for the clinical treatment of diabetic wound healing.