Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

Rebowe, Ryan E.; Rogers, Ashley; Yang, Xuebin; Kundu, Subhas C.; Smith, Thomas L.; Li, Zhongyu

doi:10.1055/s-0038-1626687

Cited by 50 publications

(48 citation statements)

References 60 publications

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“…At present, the number of patients with dysfunction after a peripheral nerve injury in China is close to 20 million, and it is increasing at a rate of nearly 2 million per year ( Fowler et al, 2015 ). In case of some special types of nerve injury, such as a nerve root laceration and avulsion, traditional surgical techniques such as tension-free nerve adventitia implantation, autologous nerve transplantation, and nerve cannula have limited efficacy ( Kubota et al, 2011 ; Rebowe et al, 2018 ; Sun et al, 2019 ). Zhang et al creatively proposed C7 nerve transposition from the healthy side to repair the paralyzed upper limb and gained nice effects ( Jiang et al, 2018 ; Zheng et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Akt/mTOR/p70S6K Signaling Pathway Regulation on Neuron Remodeling Caused by Translocation Repair

Yuan

et al. 2020

Front. Neurosci.

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Peripheral nerve injury repair has been considered a difficult problem in the field of trauma for a long time. Conventional surgical methods are not applicable in some special types of nerve injury, prompting scholars to seek to develop more effective nerve translocation repair technologies. The purpose of this study was to explore the functional state of neurons in injured lower limbs after translocation repair, with a view to preliminarily clarify the molecular mechanisms underlying this process. Eighteen Sprague–Dawley rats were divided into the normal, tibial nerve in situ repair, and common peroneal nerve transposition repair tibial nerve groups. Nerve function assessment and immunohistochemical staining of neurofilament 200 (NF-200), protein kinase B (Akt), mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase (p70S6K) in the dorsal root ganglia were performed at 12 weeks after surgery. Tibial nerve function and neuroelectrophysiological analysis, osmic acid staining, muscle strength testing, and muscle fiber staining showed that the nerve translocation repair could restore the function of the recipient nerve to a certain extent; however, the repair was not as efficient as the in situ repair. Immunohistochemical staining showed that the translocation repair resulted in changes in the microstructure of neuronal cell bodies, and the expressions of Akt, mTOR, and p70S6K in the three dorsal root ganglia groups were significantly different ( p < 0.05). This study demonstrates that the nerve translocation repair technology sets up a new reflex loop, with the corresponding neuroskeletal adjustments, in which, donor neurons dominate the recipient nerves. This indicates that nerve translocation repair technology can lead to neuronal remodeling and is important as a supplementary treatment for a peripheral nerve injury. Furthermore, the Akt/mTOR/p70S6K signaling pathway may be involved in the formation of the new neural reflex loop created as a result of the translocation repair.

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Section: Discussionmentioning

confidence: 99%

Effects of Akt/mTOR/p70S6K Signaling Pathway Regulation on Neuron Remodeling Caused by Translocation Repair

Yuan

et al. 2020

Front. Neurosci.

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“…Currently, conduits are successfully used in digital nerve repair and are an effective alternative to PNA in managing short neural gaps [6]. There are few products approved by the FDA, manufactured from type I collagen, polyglycolic acid, polycaprolactone, polyvinyl alcohol, or porcine small intestine submucosa [9]. Since they are off-theshelf products, easily stored, accessible, and biocompatible, they pose a serious alternative and direction towards the future solution of nerve repairs.…”

Section: Introductionmentioning

confidence: 99%

“…However, none of these materials exhibit perfect features as a neural bridge for sprouting axons. Thus, exploration of novel material continues, and recently poly(L-lactic acid co-ϵ-caprolactone) based scaffolds are perceived as potential candidates in that application [9].…”

Section: Introductionmentioning

confidence: 99%

Bioactive Nanofiber-based Conduits in a Peripheral Nerve Gap Management- an Animal Model Study.

Dębski

Kijeńska‐Gawrońska

Zołocińska

et al. 2020

Preprint

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Background: Peripheral nerve injuries (PNI) are trauma with severe squeals for patients’ quality of life. Currently, the gold standard of nerve reconstruction relies on primary coaptation. However, in case of a nerve gap, a reconstructive material for bridging is needed. Nerve conduits are an increasingly popular solution alternative to autografts or processed nerved allografts. The aim of the study was to examine the efficiency of a novel bioactive nanofiber-based tubular scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen, polyaniline and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model.Methods: Poly (L-lactic acid)-co-poly(ϵ-caprolactone) scaffold was optimized and enriched with collagen (COL) and polyaniline (PANI) to create final (P(LLA-CL)-COL-PANI), tubular-shaped scaffold, manufactured with electrospinning technology. Parallelly, adipose tissue from 10 Lewis rats was harvested for ASC culture. 28 inbred male Lewis rats were divided into four even groups. Each animal underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In group A, nerve gap remained untouched, in B excised trunk was rotated and used as an autograft, in C nerve stumps were secured with P(LLA-CL)-COL-PANI conduit. In the D group gap was reconstructed with P(LLA-CL)-COL-PANI conduit enriched with ASCs. After 6-months of observation rats were sacrificed. Gastrocnemius muscles (operated and non-operated side) and reconstructed sciatic nerves were harvested for analyses. Muscles were weighted and underwent histological analysis. Nerves were processed and stained immunohistochemically with NF-200 to be analyzed with dedicated software for nerve fiber count. Results: No signs of rejection or excessive fibrosis was noted. Muscle mass ratio was highest in group B (0.77±0.05), then in C (0.74±0,04) and D (0.67± 0.07). Group A showed advanced atrophy of the muscle, each intervention prevented muscle mass decrease (p<0.0001), however, ASC addition decreased efficiency vs autograft (p<0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the group with the use of conduit vs autograft (D vs B p<0.0001, C vs B p<0.001). ASC added to the conduit decreased perineurium hyperplasia.Conclusion: P(LLA-CL)-COL-PANI conduits with ASC showed promising results in managing nerve gap by decreasing muscle atrophy and providing a favorable environment for peripheral nerve regeneration.

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“…Peripheral nerve injury (PNI) imposes a large burden to medical society and over 1 million patients across the world deal with this crisis annually (Rebowe et al, 2018). This problem can lead to severe disability in 24-41% of patients suffering from a notable upper extremity PNI after only one year, in case no proper treatment is adopted (Rebowe et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

An electroactive alginate hydrogel nanocomposite reinforced by functionalized graphite nanofilaments for neural tissue engineering

Homaeigohar

Tsai

Young

et al. 2019

Carbohydrate Polymers

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To address the need to biodegradable, electroactive conduits accelerating nerve regeneration, here we develop a nanocomposite hydrogel made of alginate reinforced by citric acid functionalized graphite nanofilaments. The green, simple functionalization enhances the nanofillers distribution and their biocompatibility, as verified using mesenchymal stem cells in vitro. The uniformly distributed nanofilaments raise mechanical stability of the nanocomposite hydrogel versus the neat one up to three times. Also, the nanofilaments enable electrical contact and intercellular signaling thereby stimulating their biological activity. In vitro studies proved the biocompatibility of the nanocomposite hydrogel whereon PC12 cells proliferate and spread evidently. In vivo tests also supported applicability of the nanocomposite hydrogel for implantation within body, and the samples showed no adverse reaction and no inflammatory responses after 14 days. Conclusively, the results certify that the developed electroactive nanocomposite hydrogel is able to stimulate nerve generation and could be confidently used as a nerve conduit material.

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Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions

Cited by 50 publications

References 60 publications

Effects of Akt/mTOR/p70S6K Signaling Pathway Regulation on Neuron Remodeling Caused by Translocation Repair

Effects of Akt/mTOR/p70S6K Signaling Pathway Regulation on Neuron Remodeling Caused by Translocation Repair

Bioactive Nanofiber-based Conduits in a Peripheral Nerve Gap Management- an Animal Model Study.

An electroactive alginate hydrogel nanocomposite reinforced by functionalized graphite nanofilaments for neural tissue engineering

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