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Advances in Peripheral Nerve Regeneration
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Advances in Peripheral Nerve Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 November 2024 | Viewed by 6763

Special Issue Editor

Dr. Cinzia Fabrizi

E-Mail Website
Guest Editor
Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
Interests: glia; protease activated receptors (PARs); environmental toxins; autophagy

Special Issue Information

Dear Colleagues,

Unlike the central nervous system, the peripheral nervous system is able to regenerate promptly the following injury. Its regenerative capacity is largely related to the ability of Schwann cells to dedifferentiate and drive axonal regrowth. Peripheral nerve regeneration is, however, limited in space and time. There is, therefore, a compelling need to develop strategies aimed at promoting peripheral nerve regeneration, especially in elderly individuals and those with other concomitant diseases (e.g., diabetes). This Special Issue aims to gather contributions regarding different aspects underlying axonal regrowth following tissue injury. Articles describing the complex interplay between peripheral nerve and cancer will also be considered. ln fact, cancer can be viewed as an injury in that it damages the normal cytoarchitecture of a tissue leading to the activation of nerve regenerative mechanisms that can then promote tumor growth and dissemination.

We invite investigators to contribute original research articles and reviews which aim to describe factors favoring or limiting nerve regrowth after injury. This is a non-exhaustive list of topics that will be covered in this Special Issue:

  • Schwann cell biology
  • Biomaterials and nerve scaffolds
  • Neurotrophic and gliotrophic factors
  • Inflammatory cytokines
  • Nerve/tumor crosstalk

Dr. Cinzia Fabrizi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peripheral nerve regeneration
  • schwann cells
  • axonal regrowth
  • nerve regrowth

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Published Papers (5 papers)

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Research

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11 pages, 3038 KiB  
Article
Photosealed Neurorrhaphy Using Autologous Tissue
by Nicolò Rossi, Maria Bejar-Chapa, Riccardo Giorgino, Benjamin B. Scott, David M. Kostyra, Giuseppe M. Peretti, Mark A. Randolph and Robert W. Redmond
Int. J. Mol. Sci. 2024, 25(13), 6958; https://doi.org/10.3390/ijms25136958 - 25 Jun 2024
Viewed by 831
Abstract
Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the [...] Read more.
Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: −58.4 +/− 10.9; XHAM: −57.9 +/− 8.7; Vein: −52.4 +/− 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/− 7%; XHAM: 70 +/− 7%; Vein: 70 +/− 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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13 pages, 5637 KiB  
Article
Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves
by Maximilian Mayrhofer-Schmid, Martin Aman, Adriana C. Panayi, Floris V. Raasveld, Ulrich Kneser, Kyle R. Eberlin, Leila Harhaus and Arne Böcker
Int. J. Mol. Sci. 2024, 25(7), 3687; https://doi.org/10.3390/ijms25073687 - 26 Mar 2024
Viewed by 851
Abstract
Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to [...] Read more.
Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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18 pages, 4957 KiB  
Article
End-to-Side vs. Free Graft Nerve Reconstruction—Experimental Study on Rats
by Piotr Czarnecki, Juliusz Huber, Agnieszka Szymankiewicz-Szukała, Michał Górecki and Leszek Romanowski
Int. J. Mol. Sci. 2023, 24(13), 10428; https://doi.org/10.3390/ijms241310428 - 21 Jun 2023
Cited by 3 | Viewed by 860
Abstract
The long history of regeneration nerve research indicates many clinical problems with surgical reconstruction to be resolved. One of the promising surgical techniques in specific clinical conditions is end-to-side neurorrhaphy (ETS), described and then repeated with different efficiency in the 1990s of the [...] Read more.
The long history of regeneration nerve research indicates many clinical problems with surgical reconstruction to be resolved. One of the promising surgical techniques in specific clinical conditions is end-to-side neurorrhaphy (ETS), described and then repeated with different efficiency in the 1990s of the twentieth century. There are no reliable data on the quality of recipient nerve regeneration, possible donor nerve damage, and epineural window technique necessary to be performed. This research attempts to evaluate the possible regeneration after end-to-side neurorrhaphy, its quality, potential donor nerve damage, and the influence of epineural windows on regeneration efficiency. Forty-five female Wistar rats were divided into three equal groups, and various surgical technics were applied: A—ETS without epineural window, B—ETS with epineural window, and C—free graft reconstruction. The right peroneal nerve was operated on, and the tibial nerve was selected as a donor. After 24 weeks, the regeneration was evaluated by (1) footprint analysis every two weeks with PFI (peroneal nerve function index), TFI (tibial nerve function index), and SFI (sciatic nerve function index) calculations; (2) the amplitude and latency measurements of motor evoked potentials parameters recorded on both sides of the peroneal and tibial nerves when electroneurography with direct sciatic nerve electrical stimulation and indirect magnetic stimulation were applied; (3) histomorphometry with digital conversion of a transverse semithin nerve section, with axon count, fibers diameter, and calculation of axon area with a semiautomated method were performed. There was no statistically significant difference between the groups investigated in all the parameters. The functional indexes stabilized after eight weeks (PFI) and six weeks (TFI and SFI) and were positively time related. The lower amplitude of tibial nerve potential in groups A and B was proven compared to the non-operated side. Neurophysiological parameters of the peroneal nerve did not differ significantly. Histomorphometry revealed significantly lower diameter and area of axons in operated peroneal nerves compared to non-operated nerves. The axon count was at a normal level in every group. Tibial nerve parameters did not differ from non-operated values. Regeneration of the peroneal nerve after ETS was ascertained to be at the same level as in the case of free graft reconstruction. Peroneal nerves after ETS and free graft reconstruction were ascertained to have a lower diameter and area than non-operated ones. The technique of an epineural window does not influence the regeneration result of the peroneal nerve. The tibial nerve motor evoked potentials were characterized by lower amplitudes in ETS groups, which could indicate axonal impairment. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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Review

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11 pages, 3768 KiB  
Review
Cell Heterogeneity and Variability in Peripheral Nerve after Injury
by Zhixian Ren, Ya Tan and Lili Zhao
Int. J. Mol. Sci. 2024, 25(6), 3511; https://doi.org/10.3390/ijms25063511 - 20 Mar 2024
Viewed by 1095
Abstract
With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been extensively studied, the cellular composition of the peripheral nerve has gradually been revealed. By summarizing the current sequencing [...] Read more.
With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been extensively studied, the cellular composition of the peripheral nerve has gradually been revealed. By summarizing the current sequencing data, we compile the heterogeneities of cells that have been reported in the peripheral nerves, mainly the sciatic nerve. The cellular variability of Schwann cells, fibroblasts, immune cells, and endothelial cells during development and disease has been discussed in this review. The discovery of the architecture of peripheral nerves after injury benefits the understanding of cellular complexity in the nervous system, as well as the construction of tissue engineering nerves for nerve repair and axon regeneration. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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16 pages, 1684 KiB  
Review
Bridging Gaps in Peripheral Nerves: From Current Strategies to Future Perspectives in Conduit Design
by Elena Stocco, Silvia Barbon, Aron Emmi, Cesare Tiengo, Veronica Macchi, Raffaele De Caro and Andrea Porzionato
Int. J. Mol. Sci. 2023, 24(11), 9170; https://doi.org/10.3390/ijms24119170 - 24 May 2023
Cited by 18 | Viewed by 2576
Abstract
In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance [...] Read more.
In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance®; human origin), and hollow nerve conduits. There are eleven commercial hollow conduits approved for clinical, and they consist of devices made of a non-biodegradable synthetic polymer (polyvinyl alcohol), biodegradable synthetic polymers (poly(DL-lactide-ε-caprolactone); polyglycolic acid), and biodegradable natural polymers (collagen type I with/without glycosaminoglycan; chitosan; porcine small intestinal submucosa); different resorption times are available for resorbable guides, ranging from three months to four years. Unfortunately, anatomical/functional nerve regeneration requirements are not satisfied by any of the possible alternatives; to date, focusing on wall and/or inner lumen organization/functionalization seems to be the most promising strategy for next-generation device fabrication. Porous or grooved walls as well as multichannel lumens and luminal fillers are the most intriguing options, eventually also including the addition of cells (Schwann cells, bone marrow-derived, and adipose tissue derived stem cells) to support nerve regeneration. This review aims to describe common alternatives for severe PNI recovery with a highlight of future conduits. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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