Review Article

Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration

Authors: Rui Li1,2, Duo-hui Li1, Hong-yu Zhang1, Jian Wang3, Xiao-kun Li1, Jian Xiao1,3
1 Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
2 School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China
3 Department of Peripheral Neurosurgery, The First Affiliated Hospital, Wenzhou, Medical University, Wenzhou 325000, China
Correspondence to: Xiao-kun Li: xiaokunli@163.net, Jian Xiao: xfxj2000@126.com,
DOI: 10.1038/s41401-019-0338-1
Received: 25 July 2019
Accepted: 20 November 2019
Advance online: 2 March 2020

Abstract

Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‐life and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized.
Keywords: growth factors; peripheral nerve injury; nerve conduits; signaling cascade; axonal regeneration; nerve growth factor; basic fibroblast growth factor

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