Mechanics-Electro-Adaptive Multifunctional Bioactive Nanocomposites Hydrogel for Inducing Spinal Cord Regeneration

• A mechanics-electro-biomimetic multifunctional hydrogel was reported. • The hydrogel exhibited biocompatibility, biodegradation and antiinflammation. • The hydrogel can efficiently promote remyelination and axon regeneration. Traumatic spinal cord injury (SCI) is one of the most serious injuries, which will cause severe sensory and motor obstacles. The current effective treatment methods remain a worldwide challenge for both clinic and research. The lack of electrical signal conduction and cell growth microenvironment in SCI is one of the main obstacles that inhibit spinal cord regeneration. Herein, we report a multifunctional polycitrate-based nanocomposite hydrogel (PMEAC) scaffold with spinal cord-biomimetic mechanical and electrical properties for promoting spinal cord repair and regeneration. PMEAC scaffolds were prepared using poly(citrate-maleic)-ε-polylysine (PME) and multi-walled carbon nanotubes (MWCNT) by the facile self-crosslinking route. PMEAC scaffolds possessed multifunctional properties including injectability, self-healing ability, tissue-adhesiveness, broad-spectrum antibacterial property and UV-shielding performance, especially the biomimetic mechanical modulus (G’ = 291.69 Pa) and electroconductivity (0.15 S/m) with spinal cord tissue. PMEAC scaffolds also exhibited good cytocompatibility, hemocompatibility and biodegradability. In vivo results from a spinal cord defect model showed that PMEAC scaffolds could significantly improve locomotion recovery (BBB score 6–7), reduce inflammation, promote remyelination and axon regeneration after SCI. This study showed that multifunctional bioactive biomaterials with mechanics-electro-biomimetic properties should be the effective strategy to promote SCI recovery and regeneration.