IntroductionElectrical stimulation offers a drug-free alternative for the treatment of many neurological conditions, such as chronic pain. However, it is not easy to selectively activate afferent or efferent fibers of mixed nerves, nor their functional subtypes. Optogenetics overcomes these issues by controlling activity selectively in genetically modified fibers, however the reliability of responses to light are poor compared to electrical stimulation and the high intensities of light required present considerable translational challenges. In this study we employed a combined protocol of optical and electrical stimulation to the sciatic nerve in an optogenetic mouse model to allow for better selectivity, efficiency, and safety to overcome fundamental limitations of electrical-only and optical-only stimulation.MethodsThe sciatic nerve was surgically exposed in anesthetized mice (n = 12) expressing the ChR2-H134R opsin via the parvalbumin promoter. A custom-made peripheral nerve cuff electrode and a 452 nm laser-coupled optical fiber were used to elicit neural activity utilizing optical-only, electrical-only, or combined stimulation. Activation thresholds for the individual and combined responses were measured.ResultsOptically evoked responses had a conduction velocity of 34.3 m/s, consistent with ChR2-H134R expression in proprioceptive and low-threshold mechanoreceptor (Aα/Aβ) fibers which was also confirmed via immunohistochemical methods. Combined stimulation, utilizing a 1 ms near-threshold light pulse followed by an electrical pulse 0.5 ms later, approximately halved the electrical threshold for activation (p = 0.006, n = 5) and resulted in a 5.5 dB increase in the Aα/Aβ hybrid response amplitude compared to the electrical-only response at equivalent electrical levels (p = 0.003, n = 6). As a result, there was a 3.25 dB increase in the therapeutic stimulation window between the Aα/Aβ fiber and myogenic thresholds (p = 0.008, n = 4).DiscussionThe results demonstrate that light can be used to prime the optogenetically modified neural population to reside near threshold, thereby selectively reducing the electrical threshold for neural activation in these fibers. This reduces the amount of light needed for activation for increased safety and reduces potential off-target effects by only stimulating the fibers of interest. Since Aα/Aβ fibers are potential targets for neuromodulation in chronic pain conditions, these findings could be used to develop effective strategies to selectively manipulate pain transmission pathways in the periphery.

OBJECTIVE:To systematically compare the in vitro electrochemical and mechanical properties of several electrode coatings that have been reported to increase the efficacy of medical bionics devices by increasing the amount of charge that can be delivered safely to the target neural tissue. APPROACH:Smooth platinum (Pt) ring and disc electrodes were coated with reduced graphene oxide, conductive hydrogel, or electrodeposited Pt-Ir. Electrodes with coatings were compared with uncoated smooth Pt electrodes before and after an in vitro accelerated aging protocol. The various coatings were compared mechanically using the adhesion-by-tape test. Electrodes were stimulated in saline for 24 hours/day 7 days/week for 21 d at 85 °C (1.6-year equivalence) at a constant charge density of 200 µC/cm2/phase. Electrodes were graded on surface corrosion and trace analysis of Pt in the electrolyte after aging. Electrochemical measurements performed before, during, and after aging included electrochemical impedance spectroscopy, cyclic voltammetry, and charge injection limit and impedance from voltage transient recordings. MAIN RESULTS:All three coatings adhered well to smooth Pt and exhibited electrochemical advantage over smooth Pt electrodes prior to aging. After aging, graphene coated electrodes displayed a stimulation-induced increase in impedance and reduction in the charge injection limit (p   <  0.001), alongside extensive corrosion and release of Pt into the electrolyte. In contrast, both conductive hydrogel and Pt-Ir coated electrodes had smaller impedances and larger charge injection limits than smooth Pt electrodes (p   <  0.001) following aging regardless of the stimulus level and with little evidence of corrosion or Pt dissolution. SIGNIFICANCE:This study rigorously tested the mechanical and electrochemical performance of electrode coatings in vitro and provided suitable candidates for future in vivo testing.

Neural electrodes used for in vivo biomedical applications (e.g., prostheses, bionic implants) result in glial invasion, leading to the formation of a nonexcitable scar that increases the distance between neurons and electrode and increases the resistance to current flow. The result is progressive deterioration in the performance of stimulation or recording of neural activity and inevitable device failure. Also, electrodes with a 2D surface have a limited proximity to neurons. In the present study, a macroporous and fibrous 3D neural electrode is developed using poly-L-lactic acid fibrous membranes imbued with electroactive properties via a coating of the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT), using vapor phase polymerization. The electrical properties of the PEDOT-coated substrates are studied using sheet resistance and impedance. PEDOT electrode biocompatibility is assessed through in vitro assays using patch-clamp electrophysiology and calcium imaging of isolated and cultured rat hippocampal neurons. PEDOT fibers support robust normal functional development of neurons, including synaptic networking and communication. Stimulation and recording of activity in brain slices and from the surface of the brain using 3D-PEDOT fibrous electrodes are indistinguishable from recordings using conventional glass or platinum electrodes. In vivo studies reveal minimal reactive gliosis in response to electrode implantation.

Event Abstract Back to Event Microfibrous PEDOT scaffold for neural recordings Jason Marroquin1, Kun Zhou1, Bjorn Winther-Jensen1, Harry Coleman2, Helena Parkington2 and John S. Forsythe1 1 Monash University, Materials Engineering, Australia 2 Monash University, Physiology, Australia Current neural interfaces used for both recording and stimulating neurons have great potential in neurophysiological research to help understand processes, and in biomedical applications to restore some functions in the nervous system, e.g. prostheses, bionic implants. However, there presently exist serious limitations in obtaining stable, consistent and long-term stimulation or recording, mainly due to an unwanted glial response. The scar increases resistance to current flow as well as the distance between the neurons and the current source [1]. Consequently, higher electrical currents or voltages are required, which result in damage to neural tissue due to Faradaic reactions. Additionally, most neural interfaces have limited proximity to neurons (due to their 2D recording sites), which is greatly compromised once a glial response occurs [2]. In the present study, a microfibrous 3D neural electrode is under development using a PLLA electrospun template. The fibrous template was imbued with electroactive properties by coating with PEDOT, a conductive polymer, via vapour phase polymerization. The electrical properties of the PEDOT-coated substrates were studied in terms of sheet resistance measured by a 4-point probe, and scaffold morphology was investigated by scanning electron microscopy. Scaffold biocompatibility was assessed through in vitro assay of rat primary hippocampal neurons using patch clamp electrophysiology, calcium imaging (using fluorescent indicator Fluo-4) and immunocytochemistry. Importantly, the in vitro assays demonstrated normal spontaneous neural activity, indicating robust neural networking, up to 40 days in culture on PEDOT scaffolds. References:[1] Vadim, S.P., A.T. Patrick, and M.R. William, Response of brain tissue to chronically implanted neural electrodes. Journal of Neuroscience Methods, 2005. 148(1): p. 118[2] Warren, M.G., E.N. Sharon, and V.B. Ravi, Implanted Neural Interfaces: Biochallenges and Engineered Solutions. Biomedical Engineering, 2009. 11(1): p. 1-24. Keywords: in vitro, Scaffold, electric, microstructure Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Electrospinning and related technologies Citation: Marroquin J, Zhou K, Winther-Jensen B, Coleman H, Parkington H and Forsythe JS (2016). Microfibrous PEDOT scaffold for neural recordings. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01516 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers' terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jason Marroquin Kun Zhou Bjorn Winther-Jensen Harry Coleman Helena Parkington John S Forsythe Google Jason Marroquin Kun Zhou Bjorn Winther-Jensen Harry Coleman Helena Parkington John S Forsythe Google Scholar Jason Marroquin Kun Zhou Bjorn Winther-Jensen Harry Coleman Helena Parkington John S Forsythe PubMed Jason Marroquin Kun Zhou Bjorn Winther-Jensen Harry Coleman Helena Parkington John S Forsythe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A novel, high-performance Fe3O4/MWNT/Chitosan nanocomposite has been prepared by a simple solution evaporation method. A significant synergistic effect of Fe3O4 and MWNT provided enhanced electrical conductivity, mechanical properties, and thermal stability on the nanocomposites. A 5% (wt) loading of Fe3O4/MWNT in the nanocomposite increased conductivity from 5.34×10−5S/m to 1.49×10−2S/m compared to 5% (wt) MWNT loadings. The Fe3O4/MWNT/Chitosan films also exhibited increases in tensile strength and modulus of 70% and 155%, respectively. The integral procedure decomposition temperature (IPDT) was enhanced from 501°C to 568°C. These effects resulted from a number of factors: generation of a greater number of conductive channels through interactions between MWNT and Fe3O4 surfaces, a higher relative crystallinity, the antiplasticizing effects of Fe3O4, a restricted mobility and hindrance of depolymerization of the Chitosan chain segments, as well as uniform distribution, improved dispersion, and strong interfacial adhesion between the MWNT and Chitosan matrix.

In this study, graphene powders were crushed to smaller particles via cryomilling. The cryomilled graphene powders were characterized by XRD, Raman spectroscopy, TGA, and SEM. Tensile tests were performed on raw graphene/chitosan and cryomilled graphene/chitosan nanocomposites in order to investigate the cryomilling effect of graphene on the tensile properties of their corresponding nanocomposites. The results showed that cryomilling enhanced the dispersion, graphitic characteristics, and thermal stability of the graphene powders. Cryomilling graphene also showed that their corresponding chitosan nanocomposites had significant improvement in tensile properties compared to raw graphene/chitosan nanocomposites.

Nanocomposite films were made by a simple solution casting method in which multi-walled carbon nanotubes (MWCNT) and magnetite nanoparticles (Fe3O4) were used as dopant materials to enhance the electrical conductivity of chitosan nanocomposite films. The films contained fixed CNT concentrations (5, 8, and 10 wt%) and varying Fe3O4 content. It was determined that a 1:1 ratio of CNT to Fe3O4 provided optimal conductivity according to dopant material loading. X- ray diffraction patterns for the nanocomposite films, were determined to investigate their chemical and phase composition, revealed that nanoparticle agglomeration occurred at high Fe3O4 loadings, which hindered the synergistic effect of the doping materials on the conductivity of the films.