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Wire Electrodes Embedded in Artificial Conduit for Long-term Monitoring of the Peripheral Nerve Signal.

ABSTRACT: Massive efforts to develop neural interfaces have been made for controlling prosthetic limbs according to the will of the patient, with the ultimate goal being long-term implantation. One of the major struggles is that the electrode's performance degrades over time due to scar formation. Herein, we have developed peripheral nerve electrodes with a cone-shaped flexible artificial conduit capable of protecting wire electrodes from scar formation. The wire electrodes, which are composed of biocompatible alloy materials, were embedded in the conduit where the inside was filled with collagen to allow the damaged nerves to regenerate into the conduit and interface with the wire electrodes. After implanting the wire electrodes into the sciatic nerve of a rat, we successfully recorded the peripheral neural signals while providing mechanical stimulation. Remarkably, we observed the external stimuli-induced nerve signals at 19 weeks after implantation. This is possibly due to axon regeneration inside our platform. To verify the tissue response of our electrodes to the sciatic nerve, we performed immunohistochemistry (IHC) and observed axon regeneration without scar tissue forming inside the conduit. Thus, our strategy has proven that our neural interface can play a significant role in the long-term monitoring of the peripheral nerve signal.

SUBMITTER: Jung W

PROVIDER: S-EPMC6471311 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Wire Electrodes Embedded in Artificial Conduit for Long-term Monitoring of the Peripheral Nerve Signal.

Jung Woohyun W Jung Sunyoung S Kim Ockchul O Park HyungDal H Choi Wonsuk W Son Donghee D Chung Seok S Kim Jinseok J

Micromachines 20190313 3

Massive efforts to develop neural interfaces have been made for controlling prosthetic limbs according to the will of the patient, with the ultimate goal being long-term implantation. One of the major struggles is that the electrode's performance degrades over time due to scar formation. Herein, we have developed peripheral nerve electrodes with a cone-shaped flexible artificial conduit capable of protecting wire electrodes from scar formation. The wire electrodes, which are composed of biocompa ...[more]

PMID: 30871203

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Project description:BackgroundEfficient 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.MethodNT-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.ResultsThe 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.ConclusionIn 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.

Dataset Information

Wire Electrodes Embedded in Artificial Conduit for Long-term Monitoring of the Peripheral Nerve Signal.

Publications

Wire Electrodes Embedded in Artificial Conduit for Long-term Monitoring of the Peripheral Nerve Signal.

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