Chitosan/PVA nanofibrous membrane loaded with cerium manganese nanoparticles/SNAP promotes wound healing in diabetes

Diabetic wounds are one of the most problematic complications among diabetic patients, often progressing to chronic, persistent ulcers that are a leading cause of amputation and disability. The constant accumulation of reactive oxygen species (ROS) at diabetic wound sites, along with bacterial infection and an excess of pro-inflammatory M1-type macrophages, are key factors contributing to the difficulty of wound healing. Nanofibrous membranes can be used directly in diabetic wounds with the dual function of adsorbing tissue exudate and releasing drugs. Cerium oxide nanoparticles can be used in nanotherapy to reduce the accumulation of chronic inflammatory substances due to their excellent antioxidant properties. The antioxidant properties can be further improved by doping with other metal elements. In this paper, we constructed a nanofibrous membrane based on cerium manganese nanoparticles (CeMn NPs) for the treatment of diabetic wounds. The nanofibrous membrane was loaded with cerium manganese nanoparticles and nitric oxide donor SNAP, named PVA-CS-CeMn NPs-SNAP nanofibrous membrane. The PVA-CS-CeMn NPs-SNAP nanofibrous membrane was able to cover the wounds of diabetic mice with slow release of CeMn NPs and SNAP. The nanoparticles could scavenge ROS accumulated at the wound site and regulate the macrophage phenotype at the wound site, increasing the proportion of anti-inflammatory M2-type macrophages. In addition, SNAP had antimicrobial and vascular regenerative effects at the wound site. Together, these synergistic effects resulted in faster wound healing and reduced tissue inflammation in diabetic mice, and no organ toxicity was observed. Overall, our results indicate that PVA-CS-CeMn NPs-SNAP nanofibrous membranes have significant potential for the treatment of diabetic wounds and provide a strong scientific basis for the development of novel diabetic wound treatment materials.