The density difference between tissue and neural probes is a key factor for glial scarring

Lind, Gustav; Linsmeier, Cecilia Eriksson; Schouenborg, Jens

doi:10.1038/srep02942

Cited by 95 publications

(89 citation statements)

References 34 publications

(68 reference statements)

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“…In this strategy, a glass cone implant with attached gold sensing wires and filled with a neurotrophic factor allowed to sample electrical activity of the newly grown axons inside the cone (Bartels et al 2008). In contrast, the use of very soft or biodegradable materials may allow electrodes to integrate into the surrounding tissue more effectively (Ware et al 2012, Lind et al 2013. For instance, small size flexible probes can be reinforced for insertion with a rigid frame made from a biodegradable carboxymethyl cellulose (Gilgunn et al 2012) or silk (Tien et al 2013), which dissolves following insertion, leaving a pliable electrode with a small footprint.…”

Section: Introductionmentioning

confidence: 99%

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

et al. 2015

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Objective-A challenge for implementing high bandwidth cortical brain-machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is timeconsuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models.Approach-Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz-1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure.Main results-RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure.Significance-ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy

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Section: Introductionmentioning

confidence: 99%

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

et al. 2015

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“…[7] Additionally, long-term breach of the highly-selective blood-brain barrier (BBB) eventually leads to secretion of neurotoxins that kill neurons proximal to the electrode, thereby diminishing the signal of interest permanently. [12] Contributing factors believed to adversely affect the quality of the electrode-tissue interface in a chronic time window include electrode size, [13,14] density of electrode material, [15] skull tethering mechanisms and associated micromotion of the implant, [16] and mechanical compliance of the electrode itself. [17,18] Considering the aforementioned characteristics, the ideal implantable electrode will be small, soft, mechanically-strong, and have a density similar to neural tissue.…”

Section: Introductionmentioning

confidence: 99%

Soft, Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

Apollo

Maturana

Tong

et al. 2015

Adv Funct Materials

129

148

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. (2015). Soft, flexible freestanding neural stimulation and recording electrodes fabricated from reduced graphene oxide. Advanced Functional Materials, 25 (23), 3551-3559. Soft, flexible freestanding neural stimulation and recording electrodes fabricated from reduced graphene oxide AbstractThere is an urgent need for conductive neural interfacing materials that exhibit mechanically compliant properties, while also retaining high strength and durability under physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are composed of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibers (40-50 μm diameter) wet-spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibers are insulated with parylene-C and laser-treated, forming "brush" electrodes with diameters over 3.5 times that of the fiber shank. The fabrication method is fast, repeatable, and scalable for high-density 3D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electrochemically and used to stimulate live retina in vitro. Additionally, the electrodes are coated in a water-soluble sugar microneedle for implantation into, and subsequent recording from, visual cortex. AbstractThere is an urgent need for conductive neural interfacing materials that exhibit mechanicallycompliant properties while also retaining high strength and durability in physiological conditions. Currently, implantable electrode systems designed to stimulate and record neural activity are comprised of rigid materials such as crystalline silicon and noble metals. While these materials are strong and chemically stable, their intrinsic stiffness and density induce glial scarring and eventual loss of electrode function in vivo. Conductive composites, such as polymers and hydrogels, have excellent electrochemical and mechanical properties, but are electrodeposited onto rigid and dense metallic substrates. In the work described here, strong and conductive microfibres (40-50 µm diameter) wet-spun from liquid crystalline dispersions of graphene oxide are fabricated into freestanding neural stimulation electrodes. The fibres were insulated with parylene-C and laser-treated, forming "brush" electrodes with diameters over 3.5 times that of the fibre shank. The fabrication method is fast, repeatable, and scalable for high density 3-D array structures and does not require additional welding or attachment of larger electrodes to wires. The electrodes are characterized electroch...

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“…Implantable electrical probes can provide advantages for high-spatiotemporalresolution neural recordings independent of probing depth compared with other techniques (6). However, conventional implanted electrical probes, such as silicon and microwire probes (13,14), generally exhibit immune responses that lead to glial scar formation and neuronal cell depletion at the interfacial tissue/probe region (15)(16)(17)(18).…”

mentioning

confidence: 99%

“…Recent studies have investigated the potential advantages of reducing mechanical stiffness (19)(20)(21), feature sizes (22), as well as density of the material used for fabrication of probes (15) in terms of reduced gliosis. For example, polymer fiber-based neural probes with bending stiffness values ca.…”

mentioning

confidence: 99%

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Zhou

Hong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

191

211

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Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

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The density difference between tissue and neural probes is a key factor for glial scarring

Cited by 95 publications

References 34 publications

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

Soft, Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

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