Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation

Zuo, Kevin J.; Gordon, Tessa; Chan, K. Ming; Borschel, Gregory H.

doi:10.1016/j.expneurol.2020.113397

Cited by 114 publications

(107 citation statements)

References 127 publications

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“…Likewise, we also observed activation of PI3K/AKT and MAPK signaling pathways, along with other interconnected pathways, including T cell receptor signaling, Toll-like receptor signaling, TNF signaling, IL-17 signaling, FoxO signaling, and focal adhesion pathways, upon stimulation of corneal epithelial cells with oscillating EFs. In addition, electric stimulation upregulates expression of RAGs, increases neurotrophin signaling, accelerates axon guidance and outgrowth during peripheral nerve regeneration [25,[54][55][56][57], and is also known to activate axon guidance, along with various metabolic and signaling pathways that play crucial interconnecting roles during axon regeneration [17,[57][58][59]. Accordingly, our gene array data analysis also showed activation of similar pathways during AC EF stimulation of corneal epithelial cells.…”

Section: Discussionsupporting

confidence: 60%

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

Kowtharapu

Damaraju

Singh

et al. 2021

Genes

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In cells, intrinsic endogenous direct current (DC) electric fields (EFs) serve as morphogenetic cues and are necessary for several important cellular responses including activation of multiple signaling pathways, cell migration, tissue regeneration and wound healing. Endogenous DC EFs, generated spontaneously following injury in physiological conditions, directly correlate with wound healing rate, and different cell types respond to these EFs via directional orientation and migration. Application of external DC EFs results in electrode polarity and is known to activate intracellular signaling events in specific direction. In contrast, alternating current (AC) EFs are known to induce continuous bidirectional flow of charged particles without electrode polarity and also minimize electrode corrosion. In this context, the present study is designed to study effects of AC EFs on corneal epithelial cell gene and protein expression profiles in vitro. We performed gene and antibody arrays, analyzed the data to study specific influence of AC EFs, and report that AC EFs has no deleterious effect on epithelial cell function. Gene Ontology results, following gene and protein array data analysis, showed that AC EFs influence similar biological processes that are predominantly responsive to organic substance, chemical, or external stimuli. Both arrays activate cytokine–cytokine receptor interaction, MAPK and IL-17 signaling pathways. Further, in comparison to the gene array data, the protein array data show enrichment of diverse activated signaling pathways through several interconnecting networks.

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Section: Discussionsupporting

confidence: 60%

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

Kowtharapu

Damaraju

Singh

et al. 2021

Genes

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“…Notably, such adjustment may provide additional benefits, as recent literature suggests that appropriate stimulation of injured peripheral nerves can assist in nerve regeneration. 46 Fourth, though we tested the durability of our device over half a million taps and in simulated biological conditions over 26 days, it is necessary to verify the long-term stability and functionality of the TENG-IT device in vivo , and to adjust its design as necessary. It should ideally be possible for the device to function for many years after implantation without the need for replacement.…”

Section: Results and Discussionmentioning

confidence: 99%

Restoring Tactile Sensation Using a Triboelectric Nanogenerator

et al. 2021

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Loss of tactile sensation is a common occurrence in patients with traumatic peripheral nerve injury or soft tissue loss, but as yet, solutions for restoring such sensation are limited. Implanted neuro-prosthetics are a promising direction for tactile sensory restoration, but available technologies have substantial shortcomings, including complexity of use and of production and the need for an external power supply. In this work, we propose, fabricate, and demonstrate the use of a triboelectric nanogenerator (TENG) as a relatively simple, self-powered, biocompatible, sensitive, and flexible device for restoring tactile sensation. This integrated tactile TENG (TENG-IT) device is implanted under the skin and translates tactile pressure into electrical potential, which it relays via cuff electrodes to healthy sensory nerves, thereby stimulating them, to mimic tactile sensation. We show that the device elicits electrical activity in sensory neurons in vitro , and that the extent of this activity is dependent on the level of tactile pressure applied to the device. We subsequently demonstrate the TENG-IT in vivo , showing that it provides tactile sensation capabilities (as measured by a von Frey test) to rats in which sensation in the hindfoot was blocked through transection of the distal tibial nerve. These findings point to the substantial potential of self-powered TENG-based implanted devices as a means of restoring tactile sensation.

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“…There is still a lack of clinically effective scaffolds. This may be due to inherent nerve complexities and a need for consideration of electrical stimulation, vascularization, and exogenous biochemical molecules [ [216] , [217] , [218] , [219] ].…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

Xue

Shi

Kong

et al. 2021

Bioactive Materials

112

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The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord injury (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. The current clinical strategy of using autografts for PNI suffers from a source shortage, while the pharmacological treatment for SCI presents dissatisfactory results. Tissue engineering, as an alternative, is a promising approach for regenerating peripheral nerves and spinal cords. Through providing a beneficial environment, a scaffold is the primary element in tissue engineering. In particular, scaffolds with anisotropic structures resembling the native extracellular matrix (ECM) can effectively guide neural outgrowth and reconnection. In this review, the anatomy of peripheral nerves and spinal cords, as well as current clinical treatments for PNI and SCI, is first summarized. An overview of the critical components in peripheral nerve and spinal cord tissue engineering and the current status of regeneration approaches are also discussed. Recent advances in the fabrication of anisotropic surface patterns, aligned fibrous substrates, and 3D hydrogel scaffolds, as well as their in vitro and in vivo effects are highlighted. Finally, we summarize potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth, along with their challenges and prospects.

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Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation

Cited by 114 publications

References 127 publications

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

Restoring Tactile Sensation Using a Triboelectric Nanogenerator

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

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