Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo study in the rat sciatic nerve repair model

Abstract Background Efficient and stable delivery of neurotrophic factors (NTFs) is crucial to provide suitable microenvironment for peripheral nerve regeneration. Neurotrophin-3 (NT-3) is an important NTF during peripheral nerve regeneration which is scarce in the first few weeks of nerve defect. Exosomes are nanovesicles and have been served as promising candidate for biocarrier. In this work, NT-3 mRNA was encapsulated in adipose-derived stem cell (ADSC)-derived exosomes (ExoNT-3). These engineered exosomes were applied as NT-3 mRNA carrier and then were loaded in nerve guidance conduit (ExoNT-3-NGC) to bridge rat sciatic nerve defect. Method NT-3 mRNA was encapsulated in exosomes by forcedly expression of NT-3 mRNA in the donor ADSCs. ExoNT-3 were co-cultured with SCs in vitro; after 24 h of culture, the efficiency of NT-3 mRNA delivery was evaluated by qPCR, western blotting and ELISA. Then, ExoNT-3 were loaded in alginate hydrogel to construct the nerve guidance conduits (ExoNT-3-NGC). ExoNT-3-NGC were implanted in vivo to reconstruct 10 mm rat sciatic nerve defect. The expression of NT-3 was measured 2 weeks after the implantation operation. The sciatic nerve functional index (SFI) was examined at 2 and 8 weeks after the operation. Moreover, the therapeutic effect of ExoNT-3-NGC was also evaluated by morphology assay, immunofluorescence staining of regenerated nerves, function evaluation of gastrocnemius muscles after 8 weeks of implantation. Results The engineered exosomes could deliver NT-3 mRNA to the recipient cells efficiently and translated into functional protein. The constructed NGC could realize stable release of exosomes at least for 2 weeks. After NGC implantation in vivo, ExoNT-3-NGC group significantly promote nerve regeneration and improve the function recovery of gastrocnemius muscles compared with control exosomes (Exoempty-NGC) group. Conclusion In this work, NGC was constructed to allow exosome-mediated NT-3 mRNA delivery. After ExoNT-3-NGC implantation in vivo, the level of NT-3 could restore which enhance the nerve regeneration. Our study provide a potential approach to improve nerve regeneration.

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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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Erratum: Doxorubicin-Immersed Skeletal Muscle Grafts Promote Peripheral Nerve Regeneration Across a 10-mm Defect in the Rat Sciatic Nerve

Journal of Reconstructive Microsurgery ◽

10.1055/s-0039-3400529 ◽

2019 ◽

Vol 36 (01) ◽

pp. e1-e2

Author(s):

Hisataka Takeuchi ◽

Akio Sakamoto ◽

Ryosuke Ikeguchi ◽

Soichi Ota ◽

Hiroki Oda ◽

...

Keyword(s):

Skeletal Muscle ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

Rat Sciatic Nerve

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Effect of Arecoline on Regeneration of Injured Peripheral Nerves

The American Journal of Chinese Medicine ◽

10.1142/s0192415x13500584 ◽

2013 ◽

Vol 41 (04) ◽

pp. 865-885 ◽

Cited By ~ 4

Author(s):

Sheng-Chi Lee ◽

Chin-Chuan Tsai ◽

Chun-Hsu Yao ◽

Yuan-Man Hsu ◽

Yueh-Sheng Chen ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Peripheral Nerve Regeneration ◽

In Vitro Study ◽

Control Group ◽

Neural Cells ◽

In Vivo Evaluation

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I–II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.

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