ABSTRACT Spinal cord injury (SCI), a central nervous system injury, causes devastating lifelong disability for patients, which could be treated through effective axonal regeneration. However, axon regeneration is severely hindered by multiple pathological events, including extensive neuronal death, mitochondrial dysfunction, and inhibitory reactive oxygen species (ROS)‐enriched microenvironment. Herein, we have fabricated bioactive Ti 3 C 2 T x ‐Ce conductive hydrogel (TCH) to promote axon regeneration for SCI repair. The coordination of Ce 3+ with Ti 3 C 2 T x effectively enhances ROS scavenging property (twice that of pristine Ti 3 C 2 T x ) and boosts conductivity by 40.6%, owing to the redox‐active Ce(OH) x ‐based layer accelerates electron transfer and radical neutralization via conductive Ti 3 C 2 T x ‐Ce frameworks and Ce 3+ /Ce 4+ redox cycles. In vitro, Ti 3 C 2 T x ‐Ce nanosheets mitigate mitochondrial dysfunction by reducing mitochondrial ROS and restoring ATP production, while promoting neuronal electrical activity and activity‐dependent Ca 2+ influx to support electrical signaling and energy‐demand matching, owing to the redox‐active Ce(OH) x layer sustains intracellular redox homeostasis and electrophysiological conductivity. In vivo, TCH significantly suppresses the astrocyte reactivity by 35.6% and promotes the reconstruction of dendritic structures (twofold increase) and neuronal axons (fourfold increase) through modulation of PI3K/Akt‐S6 signaling pathway. This work highlights a multifunctional biomaterial‐mediated strategy for functional neural repair, offering promising direction for neural tissue engineering.
Wang et al. (Sat,) studied this question.