Search

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.)

Background: Employment of regenerative properties of cells at the service of nerve repair has been initiated during recent decades. Effects of local transplantation of bone marrow-derived mast cells on peripheral nerve regeneration were studied using a rat sciatic nerve transection model., Materials and Methods: A 10-mm sciatic nerve defect was bridged using a conduit chitosan-based hybrid conduit filled with BMMCs in BMMC group. In positive control group (Pos), the conduit was filled with phosphate-buffered saline alone. The regenerated nerve fibers were studied within 12 weeks after surgery. In sham-operated group, the sciatic nerve was only exposed and manipulated. In negative control (Neg) a 10-mm sciatic nerve defect was created and the nerve stumps were sutured to the adjacent muscles. The regenerated nerve fibers were studied functionally, biomechanically, histologically and immunohiscochemically., Results: Functional and biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to Pos group (p<0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in Pos group (p<0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in Pos group., Conclusions: BMMCs transplantation could be considered as a readily accessible source of cells that could improve functional recovery of transected sciatic nerve., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.)

Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair; however, results are still not comparable with the current gold standard technique “autografts”. Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair. Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance. In this study, we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model. Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks. Nevertheless, the molecular assessment in the early regeneration phase (7, 14, and 28 days) has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones. Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1, a growth factor that plays an important role in Schwann cell transdifferentiation. The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2, VEGF-A, BDNF, c-Jun, and ATF3.

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-glycolideco-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. [ABSTRACT FROM AUTHOR]

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]