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Peripheral Nerve Regeneration: From Bench to Bedside 2017

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 21981

Special Issue Editor


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Guest Editor
1. Department of Neurosurgery, Orthopaedics, Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
2. Department of Biomedical Engineering, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Interests: brain monitoring and therapeutic hypothermia; peripheral nerve injury and regeneration; translational therapeutic model for neurological injuries; development and characterization of biomaterials for bone and peripheral nerve regeneration
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2016 Special Issue, “Peripheral Nerve Regeneration: From Bench to Bedside” (https://www.mdpi.com/si/ijms/peripheral_nerve_regeneration).

Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economics costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. Although many approaches to enhance peripheral nerve regeneration have not outperformed the ‘gold standard' set by autograft procedures, studies over the past few decades have resulted in several clinically available bioabsorbable conduits and novel peripheral nerve interfaces. Among the most exciting research areas, stem cell biology recently burst out and holds significant promise in the repair of neurological injuries. The understanding of stem cell differentiation, homing, neurotrophic factors secretion and novel repair material, and the ability to mobilize endogenous stem cells to assist peripheral nerve regeneration constitute key points of research interest in nerve regeneration.

The goal of this special issue is to provide a summary of the field, describe its impact as well as introduce the recent advances in the basic and translational research of peripheral nerve injury from bench to bedside. We invite authors to submit original research and review articles related to peripheral nerve injury; mainly basic and translational research, but also clinical studies. We are interested in articles that explore the advances in neuroengineering and latest technologies in promoting peripheral nerve regeneration from translational model to clinical evaluation, such as electrophysiological monitoring and optogenesis technique. This issue will address novel therapeutic intervention in humans and also in animal models, and seek to determine the role of stem cells from widespread sources in the complex process of peripheral nerve regeneration.

Prof. Dr. Xiaofeng Jia
Guest Editor

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Keywords

  • peripheral nerve injury

  • nerve regeneration

  • stem cell

  • nerve scaffold

  • 3D printing

  • growth factors

  • electrophysiology

  • cell biology

  • signaling pathway

  • optogenesis

  • translational model

  • functional outcome

  • neuroengineering

  • clinical evaluation

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Related Special Issue

Published Papers (3 papers)

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Research

20 pages, 8666 KiB  
Article
Identification of Dysregulated microRNA Networks in Schwann Cell-Like Cultures Exposed to Immune Challenge: Potential Crosstalk with the Protective VIP/PACAP Neuropeptide System
by Giuseppe Musumeci, Gian Marco Leggio, Rubina Marzagalli, Ghaith Al-Badri, Filippo Drago and Alessandro Castorina
Int. J. Mol. Sci. 2018, 19(4), 981; https://doi.org/10.3390/ijms19040981 - 25 Mar 2018
Cited by 10 | Viewed by 5061
Abstract
Following peripheral nerve injury, dysregulations of certain non-coding microRNAs (miRNAs) occur in Schwann cells. Whether these alterations are the result of local inflammation and/or correlate with perturbations in the expression profile of the protective vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) system [...] Read more.
Following peripheral nerve injury, dysregulations of certain non-coding microRNAs (miRNAs) occur in Schwann cells. Whether these alterations are the result of local inflammation and/or correlate with perturbations in the expression profile of the protective vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) system is currently unknown. To address these issues, we aimed at profiling the expression of selected miRNAs in the rat RT4 Schwann cell line. Cells exposed to lipopolysaccharide (LPS), to mimic the local inflammatory milieu, were appraised by real-time qPCR, Western blot and ELISAs. We found that upon LPS treatment, levels of pro-inflammatory cytokines (IL-1β, -6, -18, -17A, MCP-1 and TNFα) increased in a time-dependent manner. Unexpectedly, the expression levels of VIP and PACAP were also increased. Conversely, levels of VPAC1 and VPAC2 receptors were reduced. Downregulated miRNAs included miR-181b, -145, -27a, -340 and -132 whereas upregulated ones were miR-21, -206, -146a, -34a, -155, -204 and -29a, respectively. Regression analyses revealed that a subset of the identified miRNAs inversely correlated with the expression of VPAC1 and VPAC2 receptors. In conclusion, these findings identified a novel subset of miRNAs that are dysregulated by immune challenge whose activities might elicit a regulatory function on the VIP/PACAP system. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside 2017)
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20 pages, 11113 KiB  
Article
Neurotropin® Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model
by Hozo Matsuoka, Hiroyuki Tanaka, Junichi Sayanagi, Toru Iwahashi, Koji Suzuki, Shunsuke Nishimoto, Kiyoshi Okada, Tsuyoshi Murase and Hideki Yoshikawa
Int. J. Mol. Sci. 2018, 19(2), 516; https://doi.org/10.3390/ijms19020516 - 8 Feb 2018
Cited by 15 | Viewed by 8283
Abstract
Neurotropin® (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study [...] Read more.
Neurotropin® (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study was to investigate the effects of NTP on Schwann cells (SCs) in vitro and in vivo, which play an important role in peripheral nerve regeneration. In SCs, NTP upregulated protein kinase B (AKT) activity and Krox20 and downregulated extracellular signal-regulated kinase1/2 activity under both growth and differentiation conditions, enhanced the expression of myelin basic protein and protein zero under the differentiation condition. In a co-culture of dorsal root ganglion neurons and SCs, NTP accelerated myelination of SCs. To further investigate the influence of NTP on SCs in vivo, lysophosphatidylcholine was injected into the rat sciatic nerve, leading to the focal demyelination. After demyelination, NTP was administered systemically with an osmotic pump for one week. NTP improved the ratio of myelinated axons and motor, sensory, and electrophysiological function. These findings reveal novel effects of NTP on SCs differentiation in vitro and in vivo, and indicate NTP as a promising treatment option for peripheral nerve injuries and demyelinating diseases. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside 2017)
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13202 KiB  
Article
Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration
by Caroline Kohn-Polster, Divya Bhatnagar, Derek J. Woloszyn, Matthew Richtmyer, Annett Starke, Alexandra H. Springwald, Sandra Franz, Michaela Schulz-Siegmund, Hilton M. Kaplan, Joachim Kohn and Michael C. Hacker
Int. J. Mol. Sci. 2017, 18(5), 1104; https://doi.org/10.3390/ijms18051104 - 21 May 2017
Cited by 15 | Viewed by 7658
Abstract
Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing [...] Read more.
Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR. Full article
(This article belongs to the Special Issue Peripheral Nerve Regeneration: From Bench to Bedside 2017)
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