Oxygen-Releasing Microneedle Promotes Diabetic Wound By Regulating Hypoxic Microenvironment

Diabetic wound healing presents a global clinical challenge due to a characteristic pathological microenvironment characterized by hypoxia, persistent inflammation, and impaired angiogenesis. To address these limitations, this study engineered a microneedle (MXene/TA-Ce@Hb MN) to accelerate diabetic wound repair. An oxygen-releasing microneedle (MXene/TA-Ce@Hb MN) was developed to accelerate diabetic wound healing. The microneedle was synthesized and characterized using SEM, FTIR, and UV-vis spectroscopy, with its oxygen-release capacity quantitatively validated. The microneedle exhibited biocompatibility, antimicrobial activity, antioxidant effects, immunomodulatory properties, and pro-angiogenic functions, as demonstrated through live-dead cell staining, CCK-8 assays, bacterial plate cultures, DCFH-DA(ROS) detection, and immunofluorescence imaging. In vivo experiments confirmed the microneedle’s efficacy in promoting infected wound repair. The MXene+TA-Ce@Hb MN was synthesized and validated for its capacity to release oxygen (O2) continuously, effectively alleviating hypoxia and oxidative stress in diabetic wounds. In vitro and in vivo experiments demonstrated that the microneedle improves the hypoxic microenvironment through sustained O2 release, thereby activating the extracellular signal-regulated kinase (ERK1/2) pathway to enhance cell migration and angiogenesis. Additionally, it combats bacterial infections and regulate the immune microenvironment to accelerate wound healing. The MXene+TA-Ce@Hb MN designed in this project will be used as a novel combined strategy to synergistically promote diabetic wound repair by improving the hypoxic microenvironment, pro-angiogenesis, and modulating macrophage behavior, which will provide a new strategy and new materials for the clinical treatment of diabetic wounds.