scholarly journals The Efficacy of a Scaffold-free Bio 3D Conduit Developed from Autologous Dermal Fibroblasts on Peripheral Nerve Regeneration in a Canine Ulnar Nerve Injury Model: A Preclinical Proof-of-Concept Study

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1231-1241 ◽  
Author(s):  
Sadaki Mitsuzawa ◽  
Ryosuke Ikeguchi ◽  
Tomoki Aoyama ◽  
Hisataka Takeuchi ◽  
Hirofumi Yurie ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Ulnar Nerve ◽  
Nerve Fibers ◽  
Dermal Fibroblasts ◽  
Alternative Methods ◽  
Segmental Nerve ◽  
Injury Model ◽  
Ulnar Nerve Injury

Autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects. To overcome the inevitable disadvantages of the original method, alternative methods such as the tubulization technique have been developed. Several studies have investigated the characteristics of an ideal nerve conduit in terms of supportive cells, scaffolds, growth factors, and vascularity. Previously, we confirmed that biological scaffold-free conduits fabricated from human dermal fibroblasts promote nerve regeneration in a rat sciatic nerve injury model. The purpose of this study is to evaluate the feasibility of biological scaffold-free conduits composed of autologous dermal fibroblasts using a large-animal model. Six male beagle dogs were used in this study. Eight weeks before surgery, dermal fibroblasts were harvested from their groin skin and grown in culture. Bio 3D conduits were assembled from proliferating dermal fibroblasts using a Bio 3D printer. The ulnar nerve in each dog’s forelimb was exposed under general anesthesia and sharply cut to create a 5 mm interstump gap, which was bridged by the prepared 8 mm Bio 3D conduit. Ten weeks after surgery, nerve regeneration was investigated. Electrophysiological studies detected compound muscle action potentials (CMAPs) of the hypothenar muscles and motor nerve conduction velocity (MNCV) in all animals. Macroscopic observation showed regenerated ulnar nerves. Low-level hypothenar muscle atrophy was confirmed. Immunohistochemical, histological, and morphometric studies confirmed the existence of many myelinated axons through the Bio 3D conduit. No severe adverse event was reported. Hypothenar muscles were re-innervated by regenerated nerve fibers through the Bio 3D conduit. The scaffold-free Bio 3D conduit fabricated from autologous dermal fibroblasts is effective for nerve regeneration in a canine ulnar nerve injury model. This technology was feasible as a treatment for peripheral nerve injury and segmental nerve defects in a preclinical setting.

scholarly journals Nogo-C Inhibits Peripheral Nerve Regeneration by Regulating Schwann Cell Apoptosis and Dedifferentiation

2021 ◽  
Vol 14 ◽  
Author(s):  
Bo Jia ◽  
Wei Huang ◽  
Yu Wang ◽  
Peng Zhang ◽  
Zhiwei Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Apoptosis ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Cell Dedifferentiation

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.

Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery

Hand ◽  
2021 ◽  
pp. 155894472110031
Author(s):  
Blair R. Peters ◽  
Matthew D. Wood ◽  
Daniel A. Hunter ◽  
Susan E. Mackinnon
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Ulnar Nerve ◽  
Current Literature ◽  
Axonal Regeneration ◽  
Large Diameter ◽  
Nerve Injuries ◽  
Myelinated Axons ◽  
Acellular Nerve Allograft ◽  
Ulnar Nerve Injury

Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts. Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination. Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft. Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered.

Effects of Hedysari Polysaccharides on Regeneration and Function Recovery Following Peripheral Nerve Injury in Rats

2009 ◽  
Vol 37 (01) ◽  
pp. 57-67 ◽  
Author(s):  
Shao-Yin Wei ◽  
Pei-Xun Zhang ◽  
Na Han ◽  
Yu Dang ◽  
Hong-Bo Zhang ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Function Index ◽  
Main Component ◽  
And Function

It has been demonstrated that aqueous extract of Radix Hedysari Prescription and modified Radix Hedysari Prescription could improve the regeneration of injured peripheral nerve. Radix Hedysari is a main component in these two formulas. We hypothesized that Hedysari polysaccharides (HPS), a main active ingredient, could also enhance peripheral nerve regeneration after nerve injury in adult animals. In the present study, we examined the effects of HPS on sciatic nerve regeneration for 6 weeks following clamping in rats (administrated orally of 2 ml HPS liquid daily, 0.25 g/ml). The results showed that HPS was able to enhance sciatic function index (SFI) value, tibial function index (TFI) value, peroneal nerve function index (PFI) value, conduction velocity, and the number of regenerated myelinated nerve fibers, suggesting the potential clinical application of HPS for the treatment of peripheral nerve injury in humans.

Ulnar nerve injury with martin-gruber anastomosis

1987 ◽  
Vol 10 (1) ◽  
pp. 37-39 ◽  
Author(s):  
L. Duinslaeger ◽  
A. DeBacker ◽  
L. Ceulemans ◽  
P. Wylock
Keyword(s):  
Nerve Injury ◽  
Ulnar Nerve ◽  
Ulnar Nerve Injury

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Fluorescent Protein ◽  
Control Groups ◽  
Myelinated Axons ◽  
Segmental Nerve ◽  
Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

Characteristics of peripheral nerve regeneration following a second nerve injury and repair

2012 ◽  
Vol 40 (4) ◽  
pp. 296-302
Author(s):  
Yanhua Wang ◽  
Peixun Zhang ◽  
Xiaofeng Yin ◽  
Jianping Peng ◽  
Yuhui Kou ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Injury And Repair
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