| Background: Spinal cord injury(SCI)is usually caused by trauma,disease,or degeneration.Trauma is the most important cause of SCI.SCI usually results in partial or complete loss of sensation or movement in the limbs,and severe SCI can affect blood pressure,heart rate,and respiration.In recent years,researchers have used various biologic agents and stem cell approaches for SCI repair,and although some results have been obtained in animal trials,few have had true clinical applications.Some trials have shown that epidural electrical stimulation(EES)can improve motor function and promote nerve tissue healing in patients with spinal cord injury.However,previously developed EES single-point or single-parameter pattern stimulation failed to replicate the closed-loop pattern of sensory and motor electrical signals required for normal limb activity.Second,conventional stimulation is not effective in promoting true functional regeneration of spinal cord neurons.New biomaterials and sophisticated energy technologies have driven the development of electrical stimulation devices.Conventional EES still requires battery power,which takes up more than 80% of the overall space of the implanted device.This significantly increases the size of the implant in the body.EES stimulators powered by lithium batteries are much larger and require further surgery to replace the batteries every few months to a year.Scientists have been exploring green electrical energy to solve the problems associated with the large size and limited storage capacity of conventional batteries.Spinal cord injury(SCI)disrupts neuronal relay circuits and leads to limb paralysis.Although epidural electrical stimulation is a treatment for spinal cord injury,the mode of electrical stimulation and the ability to sustain self-power are key factors affecting its efficacy and clinical translation.Objective: Based on the principle of friction-induced electricity,we developed a novel bionic Z-type nano-frictional electrical generator(BZ-TENG),which can convert joint flexion and extension kinetic energy into electrical energy when implanted in the posterior side of the rat elbow joint.In addition,we designed an innovative electrical stimulation mode to transfer the current generated by BZ-TENG to the sciatic nerve and lateral spinal cord,which we named sensory-motor coupled electrical stimulation(SMCS).The proposed BZ-TENG strategy provides an intelligent bioadaptive and sustainable in vivo power source in combination with the SMCS modality.The purpose of this experiment was to experimentally explore whether the above strategy could improve the recovery of motor and sensory functions in SCI rats.Methods: The implantable BZ-TENG is a fully encapsulated device consisting of a polyethylene terephthalate friction layer(PET)with a micro-nano structure and a polytetrafluoroethylene layer(PTFE)embedded in a single-walled sodium carbon rice tube(CNT).The electrical properties of BZ-TENG were tested by electrical equipment such as oscilloscope and voltmeter,and the dorsal root ganglion neurons(DRG)were electrically stimulated by making electrical stimulation dishes,and the cell viability of neurons was measured using the Cell Viability/Cytotoxicity Assay Kit and TUNEL Apoptosis Assay Kit after the completion of electrical stimulation.78)female SD rats,purchased from the Experimental Animal Center of Xi’an Jiaotong University,Shaanxi,China.All experimental procedures were ethically approved by the Animal Experimentation Committee of the Red Cross Hospital of Xi’an Jiaotong University.The rats were anesthetized by intraperitoneal injection of 1% sodium pentobarbital solution(40 mg kg-1),and the spinal cord was exposed by removing the T10 vertebral plate,and the SCI model was established by contusion of the spinal cord using vascular forceps for1 min.the T10 contusion rats were randomly divided into three groups: spinal cord injury group(SCI,n=24),spinal cord epidural stimulation alone group(BZ-TENG-ESA,n=24),and spinal cord EES combined with sciatic nerve electrical stimulation group(BZ-TENG-SMCS,n=24).Nanofriction generators and stimulation electrodes were implanted into the right knee joint,spinal cord and sciatic nerve of rats.Rats were injected with BDA one week before perfusion for cis-tracking.After BDA injection,2 μl of 0.5% CTB-Alexa488 solution was injected on both sides of the sciatic nerve in rats for retrograde tracing of sensory conduction bundles.In addition,spinal cord nerves,myelin sheaths,synapses,and glial cells were labeled by antibodies against TUJ-1,GFAP,NF,Syn,and MBP.The spinal cord was photographed electron microscopically and the muscle fiber area cross-sectional ratio and motor end plate area were calculated using Image J software,and motor evoked potentials(MEP)and sensory evoked potentials(SEP)were measured using the Neuro Exam M-800 data acquisition and analysis system.The frequency and quality of hindlimb movements and forelimb/hindlimb coordination were assessed using the Basso,Beattie and Bresnahan(BBB)scale for each group.footprint,basic motor behavior and coordination during continuous movement.Results: We designed a BZ-TENG consisting of a PET film with a micro-nano structure and a PTFE film embedded with CNT as a friction layer.The BZ-TENG device fits well with the dimensions of the rat elbow joint and does not affect the joint motion.We also conducted repeated compression experiments on the BZ-TENG device by heating and bending it into a Z-shaped structure to fit the rat elbow joint,and the Z-shaped structure of the BZ-TENG was very stable and durable.Verify the power generation performance of BZ-TENG.It was found that the open-circuit voltage(Voc)of BZ-TENG has a stable output of 15.00 V peak positive voltage and equivalent peak negative voltage(Figure 2a).The short-circuit current(Isc)showed a similar pattern with a stable peak current around 1.50 μA.No decrease in rat activity was observed after BZ-TENG device implantation,indicating that BZ-TENG could better match the joint activity.The ability of BZ-TENG to activate the sensorimotor transmission pathway was demonstrated by detecting sensory evoked potentials(SEP)and motor evoked potentials(MEP)generated during flexion and extension movements of the elbow joint in normal rats after implantation.The good histocompatibility of the BZ-TENG device was well illustrated by the results of the assessment of inflammation.These results indicate that the electrical stimulation signals generated by BZ-TENG not only did not damage neurons but also significantly promoted axonal growth.the BZ-TENG-SMCS electrical stimulation method reduced glial scar formation and improved spinal cord regeneration compared to epidural electrical stimulation alone.the BZ-TENG-SMCS significantly promoted axonal regeneration and improved axonal morphology.Compared with conventional epidural electrical stimulation alone,the BZ-TENG-SMCS electrical stimulation strategy creates a regenerative spinal cord microenvironment.Bi-directional tracing also demonstrated a good repair effect on the spinal cord.While epidural electrical stimulation alone prevented muscle atrophy in the hind limbs of rats after spinal cord injury,sensory-motor nerve coupling electrical stimulation was more prominent in inhibiting muscle atrophy after spinal cord injury.rats in the BZ-TENG-SMCS group greatly enhanced electrophysiological recovery by activating sensory-motor nerve coupling through a new stimulation pattern instead of simple dorsal epidural stimulation.Conclusion: We fabricated a novel BZ-TENG device with stable performance,high biocompatibility,and positive effects of the generated current not only on neuronal damage but also on the promotion of axonal growth.spinal epidural electrical stimulation driven by the BZ-TENG device activated the sensory-motor circuit in the injured area,thus significantly enhancing myelination of neurons in the injured area and axonal regeneration.It also further promoted neurological recovery and regeneration by reducing glial scar formation.It also has a significant effect in preventing muscle and motor endplate atrophy,and both electrophysiological and motor function analyses suggest that self-generated electrical stimulation via nano-friction generators has great potential in neuroregenerative medicine. |
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