Conductive hydrogel combined with electrical stimulation remodels the microenvironment for nerve regeneration to promote spinal cord injury repair

The secondary inflammatory response and disruption of electrical signaling following spinal cord injury (SCI) present significant challenges to neurological recovery. Modulating the inflammatory microenvironment and reconstructing the spinal cord's electrophysiological network are essential for effective SCI repair. To address these challenges, we designed a biomimetic 3D soft scaffold composed of phenylboronic acid-modified sodium alginate(Alg-PBA), dopamine-modified methacrylated gelatin(GelMA-DA), and Zn@EGCG modified MXene. This scaffold demonstrated excellent injectability, with an elastic modulus and electrical conductivity that closely matched those of native spinal cord tissue. The release of Zn@EGCG from the scaffold effectively suppressed inflammatory factors, promoted macrophage polarization toward the M2 phenotype, supported tissue regeneration, and reduced neuronal apoptosis. Simultaneously, under electrical stimulation (ES), the 3D soft scaffold generated stable electrical signals, which enhanced the differentiation of endogenous neural stem cells into neurons, thereby facilitating neural circuit reconstruction and functional motor recovery in rats with complete spinal cord transection. RNA sequencing analysis revealed that this therapeutic effect was linked to the activation of the PI3K/AKT signaling pathway. Overall, this study presents a multifunctional biomimetic 3D soft scaffold that modulates immune responses and promotes neuronal differentiation, offering a promising strategy for SCI repair.