Controlled Release Of Growth Factors "Cocktail" From Functional Self-assembling Peptide Nanofiber Hydrogels For Endogenous Neural Regeneration In Spinal Cord

Objective:The harmful micro-environment generating from spinal cord injury,such as the infiltration of inflammatory cells,the secretion of inflammatory factors,the lack of neurotrophic factors and the formation of glial scars,are important factors that hinder nerve regeneration and functional recovery.In this study,we used the self-assembled peptide nanofiber hydrogel sustained-release growth factor “cocktail”to convert the harmful micro-environment and research the recovery of motor function after spinal cord injury and the mechanism—the regeneration of axons and the activation of endogenous neural stem cells(eNSCs).Methods : In this study,using the Laminectomy model remove the 2mm of thoracic spinal cord(T9-T10).All rats were divided into three groups,F-SAP+GFs:The removed region filled out self-assembled peptide nanofiber hydrogel loaded with growth factor “cocktail”;F-SAP: Only the self-assembled peptide nanofiber hydrogel in the lesion;CTRL: only the lesion.Using Immunofluorescence,q-PCR etc.to detect micro-environment.eNSCs proliferation and newly born neuronswas identified by the bromodeoxyuridine(BrdU)injection.The motor tract was measured by biotinylated dextran amine(BDA;10kDa)anterograde tracing which injected into cerebral motor cortex be used to conform CST tract regeneration.The motor function recovery was used BBB locomotion assessment and MEP detected the recovery of motor system.Results:(1)After two weeks,the inflammatory response of SCI rats treated with F-SAP+GFs and F-SAP were reduced;At the same time,axon regeneration was obviously observed in the F-SAP+GFs group,compared to F-SAP group and CTRL group(P<0.05);Many newly neurons were born in F-SAP+GFs group,which was statistically significant compared with F-SAP group and CTRL group(P<0.05).At the same time,matureneurons participate in the reconstruction of CST motorneural networks.(2)Two months later,the CST motor tracts were significantly reestablished in the F-SAP+GFs group,not in the CTRL group.And hind-limb functions were significantly improved as compared with the rats without interventions.Conclusion: Controlled release of growth factors “cocktail” from functional self-assembling peptide nanofiber hydrogels provide a permissive micro-environment for axon regeneration and the eNSCs were induced to migrate to the spinal cord injury area,proliferate and differentiate into neurons,which together re-establish neural networks to promote the functional recovery of spinal cord injury.