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The aim of this study was to assess 17-β-estradiol (E2) influence on sciatic nerve regeneration after injury followed by a repair with chitosan conduit in ovariectomized female rats. The study was performed in 2 groups (n = 16) of rats: OVChit - after excision of a fragment of the sciatic nerve, a chitosan conduit was implanted; OVChitE10 group - additionally to chitosan conduit, shape-memory terpolymer rods based on poly(L-lactide-co-glycolide- co-trimethylene carbonate) releasing 17-β-estradiol for 20 weeks were implanted. The mean number of regenerating axons and mean fiber area were significantly greater in 17-β-estradiol-treated animals. In this group, the infiltrate of leukocytes was diminished. The presence of 17-β-estradiol receptors alpha and beta in motoneurons in the spinal cord were discovered. This may indicate the location where 17-β-estradiol affects the regeneration of the injured nerve. Estradiol released from the terpolymer rods for 20 weeks could enhance, to some extent, sciatic nerve regeneration after injury, and diminish the inflammatory reaction. In the future, 17-β-estradiol entrapped in terpolymer rods could be used in the repair of injured peripheral nerves, but there is a need for further studies., Competing Interests: The authors report no conflicts of interest in this work.

Treating peripheral nerve defects represents a clinical challenge, and nerve conduits lacking an internal scaffold lead to limited large nerve gap regeneration. Here, we bridged 10-mm sciatic nerve defects in rats with a chitosan conduit filled with 0, 0.5, or 1.0 mg of simvastatin in Pluronic F-127 hydrogel. We assessed subsequent nerve regeneration using the sciatic functional index (SFI), electrophysiological assessments, Fluoro-Gold (FG) retrograde tracing, gastrocnemius muscle mass measurements, and histological and immunohistochemical assessments of nerve regeneration. Ten weeks after implantation, the chitosan conduit filled with simvastatin/Pluronic F-127 hydrogel promoted nerve regeneration; there were significant increases in the SFI, compound muscle action potential peak amplitude, motor nerve conduction velocity, FG-labeled neuron number in the dorsal root ganglia, myelin sheath thickness, axon diameter, gastrocnemius wet weight, and muscle fiber area percentage in the gastrocnemius muscle (all p < 0.05). The expression levels of neurotrophic factors, such as pleiotrophin, hepatocyte growth factor, vascular endothelial growth factor, and glial cell line-derived neurotrophic factor, were also found to be increased. The results suggest that chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel improved peripheral nerve regeneration and functional recovery in rats, which may have been related to the increased expression of several endogenous neurotrophic factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 787-799, 2018., (© 2017 Wiley Periodicals, Inc.)

Ex vivo engineering of artificial nerve conduit is a suitable alternative clinical treatment for nerve injuries. Stem cells from human exfoliated deciduous teeth (SHEDs) have been considered as alternative sources of adult stem cells because of their potential to differentiate into multiple cell lineages. These cells, when cultured in six-well plates, exhibited a spindle fibroblastic morphology, whereas those under a dynamic culture aggregated into neurosphere-like clusters in the chitosan conduit. In this study, we confirmed that SHEDs efficiently express the neural stem cell marker nestin, the early neural cell marker β-III-tubulin, the late neural marker neuron-specific enolase and the glial cell markers glial fibrillary acidic protein (GFAP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase). The three-dimensional chitosan conduit and dynamic culture system generated fluid shear stress and enhanced nutrient transfer, promoting the differentiation of SHEDs to neural cells. In particular, the gene expressions of GFAP and CNPase increased by 28- and 53-fold, respectively. This study provides evidence for the dynamic culture of SHEDs during ex vivo neural differentiation and demonstrates its potential for cell therapy in neurological diseases. Copyright © 2013 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Introduction: Effect of whole body exposure to pulsed electromagnetic fields (PEMF) on nerve regeneration in a rat sciatic nerve transection model was assessed., Methods: Sixty male white Wistar rats were divided into four experimental groups (n = 15), randomly: In transected group (TC) left sciatic nerve was transected and stumps were fixed in adjacent muscle. In chitosan group (CHIT) the defect was bridged using a chitosan conduit filled with phosphate-buffered saline. In treatment group (CHIT/PEMF) the whole body was exposed to PEMF (0.3 mT, 2 Hz) for 4 h/day within 1-5 days. In normal control group (NC) sciatic nerve was only dissected and manipulated. Each group was subdivided into three subgroups of five animals each and nerve fibers were studied 4, 8 and 12 weeks after surgery., Results: Behavioral, functional, electrophysiological, biomechanical, gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in CHIT/PEMF than in CHIT group (p < 0.05). Immunohistochemical reactions to S-100 in CHIT/PEMF were more positive than that in CHIT group., Discussion: Whole body exposure to PEMF improved functional recovery and morphometric indices of sciatic nerve. Detailed mechanism of neuroprotective action remains to be investigated., Conclusion: PEMF combine with chitosan grafting could be considered as an effective, safe and tolerable treatment for peripheral nerve repair in clinical practice., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Regenerative properties of stem cells at the service of nerve repair have been initiated during recent decades. Effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on peripheral nerve regeneration were studied using a rat sciatic nerve transection model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit filled with SVF. In control group, chitosan conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied 4 weeks, 8 weeks, and 12 weeks after surgery. In sham-operated group, the sciatic nerve was only exposed and manipulated. Behavioral and Functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (P < 0.05). Gastrocnemius muscle mass in SVF transplanted animals was found to be significantly more than that in control group. Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers were significantly higher in SVF transplanted animals than in control group. In immunohistochemistry, location of reactions to S-100 in SVF transplanted animals was clearly more positive than that in control group. SVF transplantation combined with chitosan conduit could be considered as a readily accessible source of stromal cells that improve functional recovery of sciatic nerve., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Technological advances in diagnostic imaging, neurosurgical instrumentation, and the use of a surgical microscope have resulted in pronounced improvements in the diagnosis and repair of transected peripheral nerves. Effect of local fibroblast growth factor (FGF) on nerve regeneration was assessed. Eighty male Wistar rats were divided into four experimental groups ( n = 20), randomly: In transected group, left sciatic nerve was transected and stumps were fixed in adjacent muscle. In treatment group, defect was bridged using a chitosan conduit filled with 10 μL FGF. In chitosan conduit (CHIT) group, the conduit was filled with phosphate-buffered saline. In normal control group, sciatic nerve was exposed and manipulated. Each group was subdivided into four subgroups of five animals each and nerve fibers were studied in a 12-week period. Behavioral, functional, electrophysiological, and gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in CHIT/FGF than in CHIT group ( p < 0.05). Immunohistochemical reactions to S-100 in CHIT/FGF were more positive than that in CHIT group. FGF improved functional recovery and morphometric indices of sciatic nerve. It could be considered as an effective treatment for peripheral nerve repair in practice. [ABSTRACT FROM AUTHOR]

Objective(s): To investigate the effect of topical administration of alpha-lipoic acid into chitosan conduit on peripheral nerve regeneration using a rat sciatic nerve transection model. Materials and Methods: Forty five Wistar rats were divided into three experimental groups randomly. A 10-mm gap of sciatic nerve was bridged with a chitosan conduit following surgical preparation and anesthesia. In treatment group, the conduit was filled with 30 μl alpha-lipoic acid (10 mg/kg/bw).It was filled with 30 μl phosphate buffered saline solution in control group. In Sham group sciatic nerve was just exposed. Results: The recovery of nerve function was faster in treatment group than in control, at 4 and 8 weeks after surgery (P-value<0.05). Conduction velocity was better in treatment group than in control group at 4 and 12 weeks (P-value<0.05). Recovery index was higher in treatment group than the control group, 8 weeks after surgery (P-value <0.05). Greater nerve fiber diameter, axon diameter, and myelin sheath thickness were observed in treatment group compared to control group at 8 and 12 weeks after surgery (P-value<0.05). The immunoreactivity of regenerated axons and myelin sheath in treatment group were far more similar to sham group. Conclusion: Alpha-lipoic acid when loaded in a chitosan conduit could improve transected sciatic nerve regeneration in rat. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to propose a new method to prepare chitosan (CS) conduits with controllable diameters, which obviated the need to change the mold frequently. The prepared CS conduit had a layered structure due to the unique in-situ precipitation mechanism. The external diameter of the CS conduit was approximately equal to the inner diameter of the cylindrical glass mold, while the inner diameter of the CS conduit can be controlled by the precipitation time of CS gel in NaOH aqueous solution. When the external diameter of the CS conduit was fixed, the inner diameter of it decreased with the increase of precipitation time. Because of the enhancement effect of drying stresses from both the external surface and the inner surface during the drying process, the prepared CS conduit had a relatively high bending strength, which was more than 80MPa. [Copyright &y& Elsevier]