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1.
Acta Biomater ; 103: 81-91, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31863910

RESUMEN

Electrical stimulation of the muscle has been proven efficacious in preventing atrophy and/or reanimating paralyzed muscles. Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes (CNT) with fluorosilicone insulation. The electrode wire has a Young's modulus of 804 (±99) kPa, which better mimics the muscle tissue modulus than conventional stainless steel (SS) electrodes. Additionally, the non-metallic composition enables metal-artifact free CT and MR imaging. These soft wire (SW) electrodes present comparable electrical impedance to SS electrodes of similar geometric surface area, activate muscle at a lower threshold, and maintain stable electrical properties in vivo up to 4 weeks. Histologically, the SW electrodes elicited significantly less fibrotic encapsulation and less IBA-1 positive macrophage accumulation than the SS electrodes at one and three months. Further phenotyping the macrophages with the iNOS (pro-inflammatory) and ARG-1 (pro-healing) markers revealed significantly less presence of pro-inflammatory macrophage around SW implants at one month. By three months, there was a significant increase in pro-healing macrophages (ARG-1) around the SW implants but not around the SS implants. Furthermore, a larger number of AchR clusters closer to SW implants were found at both time points compared to SS implants. These results suggest that a softer implant encourages a more intimate and healthier electrode-tissue interface. STATEMENT OF SIGNIFICANCE: Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes with fluorosilicone insulation. This elastomeric composite results in an electrode wire with a Young's modulus mimicking that of the muscle tissue, which elicits significantly less foreign body response compared to stainless steel wires. The lack of metal in this composite also enables metal-artifact free MRI and CT imaging.


Asunto(s)
Elastómeros/química , Electrodos Implantados , Músculos/fisiología , Animales , Materiales Biocompatibles/química , Electroquímica , Imagen por Resonancia Magnética , Masculino , Músculos/diagnóstico por imagen , Ratas Sprague-Dawley , Receptores Colinérgicos/metabolismo , Microtomografía por Rayos X
2.
Acta Biomater ; 99: 72-83, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31446048

RESUMEN

The advancement of neural prostheses requires implantable neural electrodes capable of electrically stimulating or recording signals from neurons chronically. Unfortunately, the implantation injury and presence of foreign bodies lead to chronic inflammation, resulting in neuronal death in the vicinity of electrodes. A key mediator of inflammation and neuronal loss are reactive oxygen and nitrogen species (RONS). To mitigate the effect of RONS, a superoxide dismutase mimic compound, manganese(III) meso-tetrakis-(N-(2-aminoethyl)pyridinium-2-yl) porphyrin (iSODm), was synthesized to covalently attach to the neural probe surfaces. This new compound showed high catalytic superoxide scavenging activity. In microglia cell line cultures, the iSODm coating effectively reduced superoxide production and altered expression of iNOS, NADPH oxidase, and arginase. After 1 week of implantation, iSODm coated electrodes showed significantly lower expression of markers for oxidative stress immediately adjacent to the electrode surface, as well as significantly less neurons undergoing apoptosis. STATEMENT OF SIGNIFICANCE: One critical challenge in the translation of neural electrode technology to clinically viable devices for brain computer interface or deep brain stimulation applications is the chronic degradation of the device performance due to neuronal degeneration around the implants. One of the key mediators of inflammation and neuronal degeneration is reactive oxygen and nitrogen species released by injured neurons and inflammatory microglia. This research takes a biomimetic approach to synthesize a compound having similar reactivity as superoxide dismutase, which can catalytically scavenge reactive oxygen and nitrogen species, thereby reducing oxidative stress and decreasing neuronal degeneration. By immobilizing the compound covalently on the surface of neural implants, we show that the neuronal degeneration and oxidative stress around the implants is significantly reduced.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Terapia por Estimulación Eléctrica/instrumentación , Prótesis Neurales , Superóxidos/química , Animales , Apoptosis , Inflamación , Masculino , Microelectrodos , Microglía/metabolismo , Neuronas/metabolismo , Óxido Nítrico/química , Estrés Oxidativo , Oxígeno/química , Porfirinas/química , Ratas , Ratas Sprague-Dawley , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/química
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