Electroactive Functional Polymer Scaffolds Combined With Electrical Stimulation Induce Endogenous Neurogenesis To Repair Spinal Cord Injury

Objective:After spinal cord injury(SCI),due to the existence of inhibitory microenvironment and lack of inducible factors,only a small amount of neural stem cells(NSCs)migrate to the injury center and differentiate into neurons,which seriously impedes the repair of injured spinal cord.This study aims to design a bioactive polymer implant to induce endogenous nerve regeneration and repair SCI.Methods:Synthesis of two blocks,three blocks and four arms poly(Llysine)-poly(ethylene glycol)-poly(L-lysine)(PLL-PEG-PLL)and tetraaniline(TA)modified TA-poly(L-glutamic acid)-poly(ethylene glycol)-poly(L-glutamic acid)-TA(TA-PGA-PEG-PGA-TA)copolymer through ring-opening polymerization,deprotection and condensation reactions.Based on the electrostatic interaction between PLL-PEG-PLL solution and TA-PGA-PEG-PGA-TA solution,we engineered an electroactive polyionic composite hydrogel(EPCH)loaded with methylprednisolone(MP)and neurotrophin 3(NT3)in response to electrical stimulation(ES)to reverse inhibitory microenvironment and provide robust driving force to induce directional differentiation of NSCs,and explored its effect on repair and regeneration of neural tissue in an adult rat model of spinal cord hemisection.Result:The developed hydrogel showed three-dimensional porous structure and outstanding electroactivity,which can early explosive release of MP and continuously release NT3 for a long time(at least30 days).In vitro,EPCH has demonstrated the ability to induce differentiation of NSC into neurons.In vivo,EPCH loaded with MP and NT3 combined with ES can form new functional connections to promote significant recovery of motor function.Conclusion:EPCH-based comprehensive strategy can provide a good microenvironment and driving force for the repair of injured spinal cord,and is one of the most promising strategies for the treatment of central nervous system injury.