Electrospun Nanofibers-based Nerve Guidance Conduits Promote Peripheral Nerve Repair

Peripheral nerve injury is caused by trauma,illness,or surgery,and its outcomes are permanent sensory and motor disorders of muscles.The recovery effect is poor,resulting in financial losses for the person’s family and society.It is of great significance to integrate multiple guidance cues in one platform of nerve guidance conduits(NGCs)to promote axonal elongation and functional recovery for peripheral nerve repair.Here,we constructed a multi-functional electrospun fiber-based NGCs to promote nerve regeneration by combining ordered topological structure,density gradient of biomacromolecular nanoparticles,and controlled delivery of biological effectors to provide the topographical,haptotactic,and biological cues,respectively.On the graded surface of the uniaxially aligned polycaprolactone nanofibers together with the controlled release of recombinant human acidic fibroblast growth factor(a FGF),the directional neurites extension of both PC12 cells and drosal root ganglion(DRG)were significantly improved along the direction of increasing particle density.The migration and proliferation of Schwann cells were also promoted.It was confirmed that G-a FGF NGCs significantly promoted biocompatibility,cell differentiation,and neurite directional extension.G-a FGF NGCs enhanced axonal extension and remyelination after being implanted in vivo for 6 and 12 weeks to repair a 10-mm rat sciatic nerve defect,resulting in nerve regeneration not only in anatomical structure but also in functional recovery.Furthermore,we constructed a multi-functional electrospun fiber-based three-channel NGCs(G-a FGF-PGP)to promote nerve regeneration by combining topological structure,multi-channel structure,density gradient of biomacromolecular nanoparticles,and controlled delivery of biological effectors to provide the topographical,haptotactic,and biological cues,respectively.Together with the controlled release of a FGF,G-a FGF-PGP significantly improved the directional neurite extension of both PC12 cells and DRG,as well as the migration and proliferation of Schwann cells.In conclusion,the constructed multi-functional NGCs formed in this study by utilizing electrospun nanofibers provide a favorable environment for peripheral nerve regeneration and have a broad array of applications in tissue engineering repair.