REVIEW article
Front. Neurosci.
Sec. Translational Neuroscience
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1594435
Unlocking Nerve Regeneration: Electrical Stimulation and Bioscaffolds to Enhance Peripheral Nerve Regeneration
Provisionally accepted
- 1University of California, Davis, Davis, United States
- 2California Northstate University, Elk Grove, California, United States
- 3Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, California, United States
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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.
Keywords: peripheral nerve injury, Nerve Regeneration, peripheral nerve regeneration/repair, Schwann cell reprogramming, Electrical Stimulation, natural and synthetic scaffolds, bioengineered nerve conduits, Machine learning bioprinting optimization
Received: 16 Mar 2025; Accepted: 24 Apr 2025.
Copyright: © 2025 Thakkar, Mehdipour and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Vanshit Thakkar, University of California, Davis, Davis, United States
Stephano Chang, Department of Neurological Surgery, School of Medicine, University of California, Davis, Davis, 95817, California, United States
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