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.