Construction Of Anisotropic Nerve Scaffolds And Their Application In Repairing Nerve Injury

Nerve injuries are mostly caused by aging,iatrogenic side effects,and acute trauma,which can lead to the loss of sensory and motor functions or even life-long disability,seriously affecting the quality of life of patients and brings serious economic and social burdens.Nerve injury mainly includes peripheral nerve injury（PNI）and central nerve injury（CNI）.The peripheral nerve can regenerate spontaneously after injury,but the length of nerve gap,the time interval between injury and treatment,and the age of the patient all affect the functional recovery degree.On contrast,the pathology of CNI is great complex,and the relevant research progress on effective treatment of CNI is difficult and slow.In recent years,functional nerve repair scaffolds and stem cell transplantation have been widely applied in the repair and treatment of nerve injury,and some exciting results have also been achieved.However,current studies often focus only on a single regulatory factor when constructing scaffolds for nerve injury repair,such as the delivery of neurotrophic factors,the guidance of anisotropic topography,the introduction of conductive biomaterials,etc.,and the repair effect is still very limited.Among them,the design and development of anisotropic nerve repair scaffolds have attracted much attention,while the composite functional scaffolds that combine anisotropic structures with other clues need to be further developed and explored for their application in nerve injury repair.Therefore,in this paper,we constructed a conductive nerve guidance conduits（NGCs）for nerve repair by modifying Morpho butterfly wing with reduced graphene oxide（rGO）nanosheets and methacrylated gelatin（Gel MA）hydrogel encapsulated brain-derived neurotrophic factor（BDNF）.The prepared NGCs inherited the parallel-arranged micro-nano structure of the surface of the butterfly wing and the good conductivity of rGO.Additionally,due to the introduction of Gel MA hydrogel,the NGC exhibited great biocompatibility.The results showed that the modified scaffolds based on Morpho butterfly wing could induce the directional growth of nerve cells,promote the neuronal differentiation of neural stem cells and the directional arrangement of the differentiated neurons.Further,we transplanted the NGC to repair the sciatic nerve injury in rats and and evaluated its role in the repair of rat sciatic nerve injury.Consistent with the in vitro experimental results,more nerve cells could be observed in the injured region,indicating the promoted nerve regeneration by NGC.Importantly,after 8 weeks of treatment,the motor function of the hind limbs of the rats was significantly improved.These results have potential application value in the repair of peripheral nerve injury.We also constructed anisotropic hydrogels based on Fe₃O₄@Si O₂magnetic nanochains and collagen hydrogels as scaffolds for NSCs transplantation,and explored the application value of this cell-loaded scaffold in spinal cord injury repair.Our results showed that the constructed magnetically guided anisotropic hydrogel could respond to an external magnetic field with good cytocompatibility,and could induce the neural stem cells and differentiated neurons to extend along the magnetic field-guided oriented nanochain to form an anisotropic neural network,which is crucial for the nerve regeneration and directional bridging after injury.Finally,a rat spinal cord injury model was established and the effect of the magnetically responsive hydrogel loaded with neural stem cells in the repair of spinal cord injury was studied.The results showed that the anisotropic hydrogel combined with stem cell transplantation could effectively promote the nerve regeneration in the injured region and the recovery of motor function of the model rats.Our results show that anisotropic scaffolds have great application potential in nerve injury repair,and provide a new treatment strategy for spinal cord injury.