Cell Infiltrative Inner Connected Porous Hydrogel Improves Neural Stem Cell Migration and Differentiation for Functional Repair of Spinal Cord Injury

The disadvantages of cell-adaptive microenvironments and cellular diffusion out of the lesion have limited hydrogel-based scaffold transplantation treatment for neural connectivity, leading to permanent neurological disability from spinal cord injury. Herein, porous GelMA scaffold was prepared, in which the inner porous structure was optimized. The average pore size was 168 ± 71 μm with a porosity of 77.1%. The modulus of porous hydrogel was 593 ± 4 Pa compared to 1535 ± 85 Pa of bulk GelMA. The inner connected porous structure provided a cell-infiltrative matrix for neural stem cell migration and differentiation in vitro and eventually enhanced neuron differentiation and hindlimb strength and movement of animals in in vivo experiments. Furthermore, inflammation response and apoptosis were also alleviated after implantation. This work demonstrated that the porous hydrogel with appropriately connected micropores exhibit favorable cellular responses compared with traditional non-porous GelMA hydrogel. Taken together, our findings suggest that porous hydrogel is a promising scaffold for future delivery of stem cells and has prospects in material design for the treatment of spinal cord injury.