Three-dimensional electroconductive carbon nanotube-based hydrogel scaffolds enhance neural differentiation of stem cells from apical papilla

The radical treatment of neurological impairments remains a major clinical challenge. Stem cells with high neural differentiation ability delivered by electroconductive hydrogel scaffolds have demonstrated promising applications in neural tissue regeneration. However, there are still challenges in designing bioactive scaffolds with good biocompatibility, appropriate electrical conductivity, and neurogenic niche. Herein, a three-dimensional (3D) electroconductive gelatin methacryloyl-multi-walled carbon nanotube/cobalt (GelMA-MWCNTs/Co) hydrogel scaffold was fabricated by incorporating MWCNTs/Co composites into a GelMA hydrogel matrix. The surface morphology, pore size, elastic modulus, swelling ratio, and conductivity of the hydrogels were measured. GelMA-MWCNTs/Co exhibited higher electrical conductivity than GelMA-MWCNTs. Live/dead and CCK8 assays demonstrated the good biocompatibility of the hydrogel for stem cells from apical papilla (SCAP) growth and differentiation. The cells encapsulated in the GelMA-MWCNTs and GelMA-MWCNTs/Co hydrogel scaffolds exhibited significant neuronal cell-like changes and a notable level of neuronal-specific marker expression after the electrical stimulation (ES) for 7 days, compared to that in the hydrogels without ES. Notably, the neurite spreading and Tuj1 fluorescent intensity of the SCAP in the electrically conductive GelMA-MWCNTs/Co hydrogel were more prominent compared to those of the other two groups. In addition, the 3D conductive hydrogel scaffolds advanced the neural differentiation of SCAP to an earlier time point. Considering these aspects, the novel electroconductive GelMA-MWCNTs/Co hydrogel synergized with ES greatly promotes SCAP neuronal differentiation.