神经共形电子刺激器通过增强线粒体运输实现高级神经再生。

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

作者信息

Bai Hao, Zhang Siqi, Yang Huiran, Wang Jing, Chen Hongli, Li Jia, Li Lin, Yang Qian, Peng Bo, Zhu Ziyi, Ni Siyuan, Liu Keyin, Lei Wei, Tao Tiger H, Feng Yafei

机构信息

Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.

State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.

出版信息

Bioact Mater. 2024 May 24;39:287-301. doi: 10.1016/j.bioactmat.2024.05.033. eCollection 2024 Sep.

Abstract

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. 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 and insufficient 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 biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

摘要

解决周围神经缺损问题仍然是再生神经生物学中的一项重大挑战。自体移植曾是金标准治疗方法,但由于供体有限和可能形成神经瘤而受到阻碍。最近的大量研究报道了无线电子系统修复神经缺损的潜力。不幸的是,由于电极精度不足、神经卡压不佳以及基质材料生物活性不足,很少有研究能满足临床需求。在此,我们展示了一种先进的无线电神经刺激器,它基于具有优异生物可吸收性和生物相容性的水响应性自卷曲丝膜。我们构建了一种独特的双层结构,内层为定向预拉伸层,外层为普通丝膜。湿润后,内层的同时收缩和外层的膨胀实现了从二维平面到三维结构重构的可控超收缩。它能够实现形状自适应包裹以覆盖神经,克服了在导管内壁制备电极的技术障碍,并防止了因材料在水中膨胀导致的电极断裂。叉状电容样金属界面的使用增加了金属与再生神经之间的接触点,解决了过去电刺激方法效率低下和粗糙的问题。新开发的电子刺激器在修复10毫米大鼠坐骨神经缺损方面与自体移植相当有效。其潜在机制是电刺激增强了顺向线粒体运输以匹配能量需求。因此,这种新引入的装置展示了作为自体移植的可行且有效替代方案来增强周围神经修复和功能恢复的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c57/11143791/e1ca4deaa71f/ga1.jpg

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