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Excessive oxidative stress after spinal cord injury (SCI) can trigger an intensified inflammatory response, severely hindering nerve regeneration and functional recovery. Although antioxidant nanoenzymes that eliminate reactive oxygen species (ROS) and weaken the inflammatory cascade have shown potential in the treatment of spinal cord injury, the potential neurotoxicity associated with metal ions in most current nanoenzymes limits their clinical translation. This study presents a strategy based on metal-free carbon dots (D-CDs) that effectively eliminates ROS and reprograms the metabolism of macrophages through the P53 signaling pathway, thereby guiding the polarization of macrophages towards a phenotype that promotes regeneration. Additionally, a injectable dynamic hydrogel based on methane (QP hydrogel) was developed to achieve continuous local delivery of D-CDs at the injury site, maintaining an effective therapeutic concentration and enhancing clinical feasibility. In vitro experiments demonstrated that D-CDs@QP hydrogel effectively promotes M2 polarization of macrophages and enhances neurogenesis in neural stem cell populations, while inhibiting astrocyte differentiation. In a complete spinal cord injury mouse model, D-CDs@QP significantly enhanced the recovery of motor and bladder functions. This study developed a metal-free carbon nanoenzyme integrated hydrogel system that can reprogram the mitochondrial metabolism of macrophages, providing an effective strategy to combat neuroinflammation, stimulate nerve regeneration, and promote functional recovery after spinal cord injury. This research was published in ACS Nano under the title "Injectable Metal-Free Carbon Dot-Integrated Hydrogel for Regulating Inflammation via Macrophage Metabolic Reprograming in Spinal Cord Injury Therapy".
Reference News: DOI: 10.1021/acsnano.5c13627
