Ultrasmall MnOx Nanodots Catalyze Glucose for Reactive Oxygen Species-Dependent Sequential Anti-Infection and Regeneration Therapy

The management of diabetic wounds poses significant challenges due to persistent bacterial infections and chronic inflammation caused by hyperglycemia. Herein, a sequential two-phase treatment strategy involving a reactive oxygen species (ROS) burst in the first phase for anti-infection is proposed, followed by a benign level of ROS in the second phase for wound regeneration. To this end, ultra-small manganese oxide nanodots (BM-NDs) are incorporated into a gelatin methacry-lamide (GelMA) hydrogel via a ROS-responsive linker to form GelMA@BM dressing. The BM-NDs catalyze a self-cascade reaction that decomposes glucose into hydrogen peroxide, generates hydroxyl radicals (.OH), and simultaneously depletes glutathione. Upon application on diabetic wounds, BM-NDs are rapidly released from the hydrogel due to endogenous ROS exposure, leading to high levels of .OH that effectively eliminate bacteria and promote macrophage polar-ization to M1 phenotype, thereby facilitating phagocytosis of bacteria. With the consumption of glucose and degradation of BM-NDs, ROS in the wound area declines to a benign level, which stimulates polarization of M2 macrophages and promotes wound healing. This two-phase treatment strategy based on GelMA@BM dressing demonstrates potent antibacterial and pro-healing efficacy, showcasing its potential for clinical translation.

Automated summary

The management of diabetic wounds is challenging due to bacterial infections and chronic inflammation. This study proposes a two-phase treatment strategy using reactive oxygen species (ROS) to combat infection and promote wound regeneration. The strategy effectively eliminates bacteria and stimulates wound healing.