Use of electrospinning to construct biomaterials for peripheral nerve regeneration

AbstractA number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

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The Role of Current Techniques and Concepts in Peripheral Nerve Repair

Plastic Surgery International ◽

10.1155/2016/4175293 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 26

Author(s):

K. S. Houschyar ◽

A. Momeni ◽

M. N. Pyles ◽

J. Y. Cha ◽

Z. N. Maan ◽

...

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Clinical Application ◽

Functional Recovery ◽

Nerve Repair ◽

Treatment Options ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Peripheral Nerve Repair

Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies.

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Electroactive nanomaterials in the peripheral nerve regeneration

Journal of Materials Chemistry B ◽

10.1039/d1tb00686j ◽

2021 ◽

Author(s):

Xiangyun Yao ◽

Yun Qian ◽

Cunyi Fan

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

Life Quality ◽

Peripheral Nerve Injuries ◽

Human Beings ◽

Nerve Injuries

Severe peripheral nerve injuries are threatening the life quality of human beings.

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A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

Journal of The Royal Society Interface ◽

10.1098/rsif.2011.0438 ◽

2011 ◽

Vol 9 (67) ◽

pp. 202-221 ◽

Cited By ~ 309

Author(s):

W. Daly ◽

L. Yao ◽

D. Zeugolis ◽

A. Windebank ◽

A. Pandit

Keyword(s):

Peripheral Nerve ◽

Functional Recovery ◽

New Technologies ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Axonal Regrowth ◽

Recent Advances ◽

Recent Developments ◽

Microsurgical Techniques ◽

Cell Material Interactions

Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative—hollow nerve guidance conduits (NGCs)—have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell–material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.

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Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

BioMed Research International ◽

10.1155/2014/153808 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Yuki Shirosaki ◽

Satoshi Hayakawa ◽

Akiyoshi Osaka ◽

Maria A. Lopes ◽

José D. Santos ◽

...

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Nerve Fibers ◽

Porous Scaffolds ◽

Hybrid Membranes ◽

Nerve Injuries ◽

Myelinated Nerve ◽

Nerve Guides

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton’s jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration.

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Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries

Biochemical Society Transactions ◽

10.1042/bst20140004 ◽

2014 ◽

Vol 42 (3) ◽

pp. 697-701 ◽

Cited By ~ 18

Author(s):

Mallappa K. Kolar ◽

Paul J. Kingham

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Peripheral Nerve ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Donor Site ◽

Short Review ◽

Donor Site Morbidity ◽

Peripheral Nerve Injuries ◽

Nerve Injuries

Peripheral nerve injuries are a common occurrence affecting the nerves found outside the central nervous system. Complete nerve transections necessitate surgical re-anastomosis, and, in cases where there is a significant gap between the two ends of the injured nerve, bridging strategies are required to repair the defect. The current clinical gold standard is the nerve graft, but this has a number of limitations, including donor site morbidity. An active area of research is focused on developing other techniques to replace these grafts, by creating tubular nerve-guidance conduits from natural and synthetic materials, which are often supplemented with biological cues such as growth factors and regenerative cells. In the present short review, we focus on the use of adipose-tissue-derived stem cells and the possible mechanisms through which they may exert a positive influence on peripheral nerve regeneration, thereby enabling more effective nerve repair.

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Modelling-informed cell-seeded nerve repair construct designs for treating peripheral nerve injuries

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009142 ◽

2021 ◽

Vol 17 (7) ◽

pp. e1009142

Author(s):

Rachel Coy ◽

Maxime Berg ◽

James B. Phillips ◽

Rebecca J. Shipley

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Functional Recovery ◽

Nerve Tissue ◽

Diffusion Reaction ◽

Peripheral Nerve Injuries ◽

Nerve Injuries ◽

Linear Diffusion ◽

Wide Range

Millions of people worldwide are affected by peripheral nerve injuries (PNI), involving billions of dollars in healthcare costs. Common outcomes for patients include paralysis and loss of sensation, often leading to lifelong pain and disability. Engineered Neural Tissue (EngNT) is being developed as an alternative to the current treatments for large-gap PNIs that show underwhelming functional recovery in many cases. EngNT repair constructs are composed of a stabilised hydrogel cylinder, surrounded by a sheath of material, to mimic the properties of nerve tissue. The technology also enables the spatial seeding of therapeutic cells in the hydrogel to promote nerve regeneration. The identification of mechanisms leading to maximal nerve regeneration and to functional recovery is a central challenge in the design of EngNT repair constructs. Using in vivo experiments in isolation is costly and time-consuming, offering a limited insight on the mechanisms underlying the performance of a given repair construct. To bridge this gap, we derive a cell-solute model and apply it to the case of EngNT repair constructs seeded with therapeutic cells which produce vascular endothelial growth factor (VEGF) under low oxygen conditions to promote vascularisation in the construct. The model comprises a set of coupled non-linear diffusion-reaction equations describing the evolving cell population along with its interactions with oxygen and VEGF fields during the first 24h after transplant into the nerve injury site. This model allows us to evaluate a wide range of repair construct designs (e.g. cell-seeding strategy, sheath material, culture conditions), the idea being that designs performing well over a short timescale could be shortlisted for in vivo trials. In particular, our results suggest that seeding cells beyond a certain density threshold is detrimental regardless of the situation considered, opening new avenues for future nerve tissue engineering.

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IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01227-1 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Feixiang Chen ◽

Weihuang Liu ◽

Qiang Zhang ◽

Ping Wu ◽

Ao Xiao ◽

...

Keyword(s):

Bone Marrow ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Knockout Mice ◽

Inflammatory Markers ◽

Nerve Repair ◽

Peripheral Nerve Regeneration ◽

Wild Type ◽

Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

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