3D bioprinted conductive spinal cord biomimetic scaffolds for promoting neuronal differentiation of neural stem cells and repairing of spinal cord injury

Spinal cord injury (SCI) is a terrible injury of the central nervous system for which there is no ideal treatment in clinic so far. The spinal cord biomimetic scaffolds which mimic the shape and structure of native spinal cord tissue, could effectively promote the repair of SCI. However, current biomimetic scaffolds do not mimic the biological functions, especially the electrical conductivity, of spinal cord tissue, which largely limits the therapeutic effect of SCI. In this study, we have developed novel conductive hydrogels based on gelatin methacrylate (GelMA), hyaluronic acid methacrylate (HAMA) and poly(3,4-ethylenedioxythiophene): sulfonated lignin (PEDOT:LS). The incorporation of PEDOT:LS into GelMA/HAMA hydrogel matrix significantly improved the conductivity of the hydrogels. By precisely regulating the light curing time, the conductive hydrogels showed mechanical properties similar to native spinal cord tissues. Then, the conductive biomimetic scaffolds were fabricated by 3D bioprinting, and the neural stem cells (NSCs) encapsulated in the scaffolds exhibited good survival rate (higher than 90%). Compared to the non-conductive scaffolds reported, the conductive scaffolds remarkably promoted neuronal differentiation of NSCs in vitro. In a rat spinal cord complete transection model, the conductive biomimetic scaffold dramatically promoted the recovery of hindlimb motor function. Immunofluorescence staining results further showed that the conductive biomimetic scaffold effectively promoted the regeneration of neurons at the injury site, reduced the deposition of glial scar, and promoted nerve axon regeneration and myelination. Overall, the 3D bioprinting of the conductive spinal cord biomimetic scaffolds developed in this work represents a promising approach for the stem cell-based treatment of SCI.