Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration

Peripheral nerve injury (PNI) is a challenging clinical problem resulting in disabling sensorimotor deficits, which may become permanent if recovery does not take place in a timely manner. In this review, we examine recent insights into key molecular mechanisms—particularly MAPK/ERK and PI3K/Akt—tha...

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Main Authors: Vanshit Thakkar, Melod Mehdipour, Stephano Chang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1594435/full
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author Vanshit Thakkar
Melod Mehdipour
Stephano Chang
author_facet Vanshit Thakkar
Melod Mehdipour
Stephano Chang
author_sort Vanshit Thakkar
collection DOAJ
description Peripheral nerve injury (PNI) is a challenging clinical problem resulting in disabling sensorimotor deficits, which may become permanent if recovery does not take place in a timely manner. In this review, we examine recent insights into key molecular mechanisms—particularly MAPK/ERK and PI3K/Akt—that govern Wallerian degeneration, Schwann cell (SC) reprogramming, and macrophage polarization. These and other critical steps in the axonal regeneration process must be understood and navigated for a therapeutic approach to be successful. We highlight emerging therapeutic strategies, such as electrical stimulation (ES), which appears to work by activating many of these pro-regenerative gene networks, both in neurons and non-neuronal support cells. Advances in biomaterial engineering, including natural and synthetic scaffolds enriched with growth factors, also show promise in facilitating axonal regeneration across nerve gaps. We postulate that integrating optimized ES protocols with innovative scaffold designs will allow for synergies to further enhance axonal regeneration and functional recovery.
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publisher Frontiers Media S.A.
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spelling doaj-art-37e1ffa7cbf9479fac3e5d57b11488742025-08-20T01:51:55ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-05-011910.3389/fnins.2025.15944351594435Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regenerationVanshit Thakkar0Melod Mehdipour1Stephano Chang2Department of Neurobiology, Physiology, and Behavior Science, University of California, Davis, Davis, CA, United StatesCalifornia Northstate University, College of Medicine, Elk Grove, CA, United StatesDepartment of Neurological Surgery, University of California, Davis Medical Center, Sacramento, CA, United StatesPeripheral nerve injury (PNI) is a challenging clinical problem resulting in disabling sensorimotor deficits, which may become permanent if recovery does not take place in a timely manner. In this review, we examine recent insights into key molecular mechanisms—particularly MAPK/ERK and PI3K/Akt—that govern Wallerian degeneration, Schwann cell (SC) reprogramming, and macrophage polarization. These and other critical steps in the axonal regeneration process must be understood and navigated for a therapeutic approach to be successful. We highlight emerging therapeutic strategies, such as electrical stimulation (ES), which appears to work by activating many of these pro-regenerative gene networks, both in neurons and non-neuronal support cells. Advances in biomaterial engineering, including natural and synthetic scaffolds enriched with growth factors, also show promise in facilitating axonal regeneration across nerve gaps. We postulate that integrating optimized ES protocols with innovative scaffold designs will allow for synergies to further enhance axonal regeneration and functional recovery.https://www.frontiersin.org/articles/10.3389/fnins.2025.1594435/fullperipheral nerve injurynerve regenerationperipheral nerve regeneration/repairSchwann cell reprogrammingelectrical stimulationnatural and synthetic scaffolds
spellingShingle Vanshit Thakkar
Melod Mehdipour
Stephano Chang
Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
Frontiers in Neuroscience
peripheral nerve injury
nerve regeneration
peripheral nerve regeneration/repair
Schwann cell reprogramming
electrical stimulation
natural and synthetic scaffolds
title Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
title_full Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
title_fullStr Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
title_full_unstemmed Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
title_short Unlocking nerve regeneration: electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
title_sort unlocking nerve regeneration electrical stimulation and bioscaffolds to enhance peripheral nerve regeneration
topic peripheral nerve injury
nerve regeneration
peripheral nerve regeneration/repair
Schwann cell reprogramming
electrical stimulation
natural and synthetic scaffolds
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1594435/full
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AT melodmehdipour unlockingnerveregenerationelectricalstimulationandbioscaffoldstoenhanceperipheralnerveregeneration
AT stephanochang unlockingnerveregenerationelectricalstimulationandbioscaffoldstoenhanceperipheralnerveregeneration