Hydrogel Scaffold Promote Endogenous Neural Circuit Remodeling To Repair Spinal Cord Injury

Objective:After spinal cord injury in adult mammals,neurons lost in the injured area often fail to regenerate,resulting in permanent sensory and motor dysfunction.Past studies suggested that there are cells in the spinal cord which could activated by injury and express nestin,and these cells have the potential to differentiate into neurons.In this study,the application of cytokine-loaded bio-scaffolds could promote injury-activated nestin~+cells migration and differentiation,and participate in the remodeling of neural circuits in the lesion cite after spinal cord injury,thereby promoting the recovery of motor function.Methods:Tissue RNA-sequence was used to compare the RNA expression of normal and injured rat spinal cords,then screening out the relevant pathways that may affect the migration of activated cells after spinal cord injury,and the corresponding cytokine was used to verify the injury-induced nestin~+migration efficiency in vitro and in vivo.Meanwhile,neural stem cell differentiation experiments were conducted in vitro,to explored cytokine that could promote the nestin~+cells differentiate into neurons.Finally,a photo-crosslinked gelatin hydrogel scaffold was used to load the above cytokine to construct a drug sustained release system,which was implanted into a rat completed spinal cord injury model to observe the effect of the dual-factor hydrogel scaffold on neural circuit remodeling.Results:The dual-factor hydrogel scaffold was grafted into the rat completed spinal cord injury.In 10 days post injury,tissue immunofluorescence results suggested that the number of newborn nerve fibers at the lesion site was significant higher than other groups.In 8 weeks post injury,the tissue immunofluorescence results of the dual-factor hydrogel scaffold group showed that the number of mature neuronal fibers in the injured area was significantly higher than the control group and the scaffold group.Finally,behavioral score results suggested that the motor function recovery of the rats in the dual-factor group was higher than the control group and the scaffold group.Conclusion:Application of this dual-factor hydrogel scaffold after spinal cord injury could promote neurogenesis and maturation in the lesion site,then forming neural relays to participate in the remodeling of neural circuits after injury,and promoting the recovery of motor function.