Bioinspired conductive oriented nanofiber felt with efficient ROS clearance and anti-inflammation for inducing M2 macrophage polarization and accelerating spinal cord injury repair

Complete spinal cord injury (SCI) causes permanent locomotor, sensory and neurological dysfunctions. Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration, oxidative stress and massive neuronal apoptosis, the conductive oriented nanofiber felt with efficient ROS clearance, anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair. The formation of innovative Fe³⁺-PDA-PAT chelate in nanofiber felt enhances hydrophilic, antioxidant, antibacterial, hemostatic and binding factor capacities, thereby regulating immune microenvironment of SCI. With the capabilities of up-regulating COX5A and STAT6 expressions, down-regulating the expressions of IL1β, CD36, p-ERK, NFκB2 and NFκB signaling pathway proteins, the nanofiber felt attenuates oxidative stress injury, promotes M2 macrophage polarization and down-regulates inflammatory response. After implantation into complete transection SCI rats, the nanofiber felt is revealed to recruit endogenous NSCs, induce the differentiation of NSCs into neurons while inhibit astrocytes formation and inflammation, reduces glia scar, and promotes angiogenesis, remyelination and neurological functional recovery. Overall, this innovative strategy provides a facile immune regulatory system to inhibit inflammatory response and accelerate nerve regeneration after SCI, and its targeted proteins and mechanisms are first elucidated, which holds great application promise in clinical treatment of complete SCI.