Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology.Autograftsemerged as the gold-standard management,however,are hindered by limited availability and potential neuromaformation.Numerous recent studies report the potential of wireless electronic system for nerve defects repair.Unfortunately,few has met clinical needs for inadequate electrode precision,poor nerve entrapment andinsufficient bioactivity of the matrix material.Herein,we present an advanced wireless electrical nerve stimulator,based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatibleproperties.We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a generalsilk membrane as outer layer.After wetting,the simultaneous contraction of inner layer and expansion of outerlayer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration.It enablesshape-adaptive wrapping to cover around nerves,overcomes the technical obstacle of preparing electrodes on theinner wall of the conduit,and prevents electrode breakage caused by material expansion in water.The use of forkcapacitor-like metal interface increases the contact points between the metal and the regenerating nerve,solvingthe challenge of inefficient and rough electrical stimulation methods in the past.Newly developed electronicstimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts.The underlyingmechanism involves that electric stimulation enhances anterograde mitochondrial transport to matchenergy demands.This newly introduced device thereby demonstrated the potential as a viable and efficaciousalternative to autografts for enhancing peripheral nerve repair and functional recovery.