Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes

Kozai, Takashi D. Y.; Gugel, Zhannetta V.; Li, Xia; Gilgunn, Peter J.; Khilwani, Rakesh; Özdoğanlar, O. Burak; Fedder, Gary K.; Weber, Douglas J.; Cui, Xinyan Tracy

doi:10.1016/j.biomaterials.2014.07.039

Cited by 173 publications

(214 citation statements)

References 56 publications

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“…We hypothesize that this enhanced neuronal loss was caused by the stiffening shuttle used during the electrode implant procedure. 42,43 In scanning electron microscopy (SEM) images of explanted devices, we noted negligible tissue on CNT fiber microelectrodes, in contrast with substantial encapsulation around PtIr implants, which is consistent with results of chronic histology (Supplementary Figure S3). Additionally, we found no evidence of alterations in the structure of the CNT fibers, no signs of degradation at the stimulation site, and no cracks in the insulation material.…”

Section: Resultssupporting

confidence: 87%

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes

et al. 2015

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The development of microelectrodes capable of safely stimulating and recording neural activity is a critical step in the design of many prosthetic devices, brain-machine interfaces, and therapies for neurologic or nervous-system-mediated disorders. Metal electrodes are inadequate prospects for the miniaturization needed to attain neuronal-scale stimulation and recording because of their poor electrochemical properties, high stiffness, and propensity to fail due to bending fatigue. Here we demonstrate neural recording and stimulation using carbon nanotube (CNT) fiber electrodes. In vitro characterization shows that the tissue contact impedance of CNT fibers is remarkably lower than that of state-of-the-art metal electrodes, making them suitable for recording single-neuron activity without additional surface treatments. In vivo chronic studies in parkinsonian rodents show that CNT fiber microelectrodes stimulate neurons as effectively as metal electrodes with 10 times larger surface area, while eliciting a significantly reduced inflammatory response. The same CNT fiber microelectrodes can record neural activity for weeks, paving the way for the development of novel multifunctional and dynamic neural interfaces with long-term stability.

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Section: Resultssupporting

confidence: 87%

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes

et al. 2015

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“…Previous studies have demonstrated that IgG that enters the parenchyma of the CNS is sequestered by astroglia and microglia where they have been shown to remain for at least 9 months [83–85]. In addition, IgG can also be carried into the CNS by blood borne macrophages [100]. Therefore the presence of IgG in the tissue is not necessarily indicative of chronic IgG leakage, as the IgG detected may be from the initial surgical implantation.…”

Section: Discussionmentioning

confidence: 99%

Effects of caspase-1 knockout on chronic neural recording quality and longevity: Insight into cellular and molecular mechanisms of the reactive tissue response

et al. 2014

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Chronic implantation of microelectrodes into the cortex has been shown to lead to inflammatory gliosis and neuronal loss in the microenvironment immediately surrounding the probe, a hypothesized cause of neural recording failure. Caspase-1 (aka Interleukin 1β converting enzyme) is known to play a key role in both inflammation and programmed cell death, particularly in stroke and neurodegenerative diseases. Caspase-1 knockout (KO) mice are resistant to apoptosis and these mice have preserved neurologic function by reducing ischemia-induced brain injury in stroke models. Local ischemic injury can occur following neural probe insertion and thus in this study we investigated the hypothesis that caspase-1 KO mice would have less ischemic injury surrounding the neural probe. In this study, caspase-1 KO mice were implanted with chronic single shank 3mm Michigan probes into V1m cortex. Electrophysiology recording showed significantly improved single-unit recording performance (yield and signal to noise ratio) of caspase-1 KO mice compared to wild type C57B6 (WT) mice over the course of up to 6 months for the majority of the depth. The higher yield is supported by the improved neuronal survival in the caspase-1 KO mice. Impedance fluctuates over time but appears to be steadier in the caspase-1 KO especially at longer time points, suggesting milder glia scarring. These findings show that caspase-1 is a promising target for pharmacologic interventions.

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“…This loss of viable neurons at the electrode-tissue interface may contribute to signal deterioration and the eventual failure of penetrating electrodes. Therefore, to improve the long-term reliability of neural probe over time, the next generation of high-performance microelectrodes must cause a lower tissue reactivity, BBB disruption, glial response and neuronal degeneration/damage [27, 35, 37]. It is also critical to consider electrode design factors including size, shape and tethering [35, 38, 39].…”

Section: Introductionmentioning

confidence: 99%

Elastomeric and soft conducting microwires for implantable neural interfaces

et al. 2015

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Current designs for microelectrodes used for interfacing with the nervous system elicit a characteristic inflammatory response that leads to scar tissue encapsulation, electrical insulation of the electrode from the tissue and ultimately failure. Traditionally, relatively stiff materials like tungsten and silicon are employed which have mechanical properties several orders of magnitude different from neural tissue. This mechanical mismatch is thought to be a major cause of chronic inflammation and degeneration around the device. In an effort to minimize the disparity between neural interface devices and the brain, novel soft electrodes consisting of elastomers and intrinsically conducting polymers were fabricated. The physical, mechanical and electrochemical properties of these materials were extensively characterized to identify the formulations with the optimal combination of parameters including Young’s modulus, elongation at break, ultimate tensile strength, conductivity, impedance and surface charge injection. Our final electrode has a Young’s modulus of 974 kPa which is five orders of magnitude lower than tungsten and significantly lower than other polymer-based neural electrode materials. In vitro cell culture experiments demonstrated the favorable interaction between these soft materials and neurons, astrocytes and microglia, with higher neuronal attachment and a two-fold reduction in inflammatory microglia attachment on soft devices compared to stiff controls. Surface immobilization of neuronal adhesion proteins on these microwires further improved the cellular response. Finally, in vivo electrophysiology demonstrated the functionality of the elastomeric electrodes in recording single unit activity in the rodent visual cortex. The results presented provide initial evidence in support of the use of soft materials in neural interface applications.

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Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes

Cited by 173 publications

References 56 publications

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes

Effects of caspase-1 knockout on chronic neural recording quality and longevity: Insight into cellular and molecular mechanisms of the reactive tissue response

Elastomeric and soft conducting microwires for implantable neural interfaces

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