Spinal cord injury (SCI) causes irreversible neurological damage largely due to secondary processes such as ferroptosis and inflammation response, which hinder functional recovery and lack effective targeted treatments. Ferroptosis, an iron-dependent form of cell death driven by oxidative stress, and a pro-inflammatory microenvironment contribute significantly to neuronal loss after SCI. To address these challenges, we developed MCPAD, an injectable, self-healing nanocomposite hydrogel incorporating metformin-loaded PLGA nanoparticles (Met@PLGA NPs) and phenol-derived dynamic cross-linked network (CPAD). This multifunctional platform enables targeted suppression of ferroptosis and immunomodulation. In vitro, MCPAD significantly enhanced neuronal viability by regulating iron homeostasis and upregulating antioxidant defenses. In vivo, it reduced reactive oxygen species (ROS) accumulation, glial scarring, and inflammatory cytokine expression, while promoting axonal regeneration and synaptic remodeling. Treated animals exhibited greatly improved locomotor recovery and tissue preservation. Biochemical assessments confirmed systemic biosafety. These findings demonstrate the therapeutic potential of MCPAD as a biological responsive platform that reprograms the injury microenvironment to support functional neural repair after SCI.
Ze Xu,Dan Shou,Wenrong Cai,Junyao Li,Datong Wu,Tao Jiang,Yong Kong
6-Deoxy-6-arginine grafted chitosan (DAC) is cross-linked with dibenzaldehyde-functionalized polyethylene glycol (DF-PEG) via the acylhydrazone (–N=CH–) bonds, which can be utilized for the encapsulation of metformin (MET). The resultant injectable DAC/DF-PEG/MET (DDM) hydrogels highlight well-behaved antibacterial and anti-inflammatory activity as well as self-healing capability. More interestingly, the DDM hydrogels exhibit appealing dynamic self-degradability. The electrostatic attraction between DAC and DF-PEG is significantly weakened at slightly alkaline surface (pH 7.0–8.0) that is the characteristic of skin wounds, resulting in the swelling of the hydrogels and the release of MET. As the wounds gradually get healed, the skin tissue turns to be weakly acidic (pH 4.0–6.0), leading to the hydrolysis of the –N=CH– bonds between DAC and DF-PEG. Therefore, the DDM hydrogels can be dynamically self-degraded during the wound healing process. Owing to the injectability and self-healing properties, the DDM hydrogels are suitable for use as the wound dressing for the wounds in any shape. The developed DDM hydrogels also display excellent hemocompatibility and cytocompatibility, indicating that they might be a potential wound dressing for skin wounds.
危险品化学品经营许可证（带存储）