Characterization of Parylene-C degradation mechanisms: In vitro reactive accelerated aging model compared to multiyear in vivo implantation

Caldwell, Ryan; Street, Matthew G.; Sharma, Rohit; Takmakov, Pavel; Baker, Brian; Rieth, Loren

doi:10.1016/j.biomaterials.2019.119731

Cited by 67 publications

(73 citation statements)

References 62 publications

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“…Oliva et al looked at the fibrotic response of parylene-C based intraneural implants in rats over a period of more than six months and found the response larger than that of polyimide. In addition, the lifetime of parylene-C encapsulated implants is shorter than previously estimated [59]. Therefore, polyimide could be a more adequate substrate for chronic neural implants while parylene-C remains an adequate material for acute applications.…”

Section: Discussionmentioning

confidence: 91%

W:Ti Flexible Transversal Electrode Array for Peripheral Nerve Stimulation: A Feasibility Study

Silveira

Brunton

Escobedo-Cousin

et al. 2020

IEEE Trans. Neural Syst. Rehabil. Eng.

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The development of hardware for neural interfacing remains a technical challenge. We introduce a flexible, transversal intraneural tungsten:titanium electrode array for acute studies. We characterize the electrochemical properties of this new combination of tungsten and titanium using cyclic voltammetry and electrochemical impedance spectroscopy. With an in-vivo rodent study, we show that the stimulation of peripheral nerves with this electrode array is possible and that more than half of the electrode contacts can yield a stimulation selectivity index of 0.75 or higher at low stimulation currents. This feasibility study paves the way for the development of future cost-effective and easy-to-fabricate neural interfacing electrodes for acute settings, which ultimately can inform the development of technologies that enable bi-directional communication with the human nervous system.

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Section: Discussionmentioning

confidence: 91%

W:Ti Flexible Transversal Electrode Array for Peripheral Nerve Stimulation: A Feasibility Study

Silveira

Brunton

Escobedo-Cousin

et al. 2020

IEEE Trans. Neural Syst. Rehabil. Eng.

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“…In addition, [4] suggests that strong tissue reaction can be developed around parylene-C-based implants after 8-month in vivo tests, while tissue reaction to PDMS is minimal. [5] also shows oxidation and chlorine abstraction of parylene after 3.25 years of implantation. As a consequence, an additional outmost encapsulation layer with a similar mechanical property to the tissue is desired.…”

Section: Introductionmentioning

confidence: 93%

PDMS-Parylene Adhesion Improvement via Ceramic Interlayers to Strengthen the Encapsulation of Active Neural Implants

Babaroud

Dekker

Serdijn

et al. 2020

2020 42nd Annual International Conference of the IEEE Engineering in Medicine &Amp; Biology Society (EMBC)

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Parylene-C has been used as a substrate and encapsulation material for many implantable medical devices. However, to ensure the flexibility required in some applications, minimize tissue reaction, and protect parylene from degradation in vivo an additional outmost layer of polydimethylsiloxane (PDMS) is desired. In such a scenario, the adhesion of PDMS to parylene is of critical importance to prevent early failure caused by delamination in the harsh environment of the human body. Towards this goal, we propose a method based on creating chemical covalent bonds using intermediate ceramic layers as adhesion promoters between PDMS and parylene. To evaluate our concept, we prepared three different sets of samples with PDMS on parylene without and with oxygen plasma treatment (the most commonly employed method to increase adhesion), and samples with our proposed ceramic intermediate layers of silicon carbide (SiC) and silicon dioxide (SiO2). The samples were soaked in phosphate-buffered saline (PBS) solution at room temperature and were inspected under an optical microscope. To investigate the adhesion property, cross-cut tape tests and peel tests were performed. The results showed a significant improvement of the adhesion and in-soak long-term performance of our proposed encapsulation stack compared with PDMS on parylene and PDMS on plasmatreated parylene. We aim to use the proposed solution to package bare silicon chips on active implants.

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“…Mechanisms that determine threshold can be grouped into 3 categories: those related to the neural interface, those related to the generated electrical field, and those related to the physiological status of the end-organ. Factors that determine the neural interface include surgical technique 2, 11 , foreign body response to a long-term implanted electrode 1, 8 19 , and degradation of the electrode itself 20 . Factors influencing the generated electrical field include electrode geometry 21 22 , electrode orientation relative to the stimulated neural elements 17, 21, 23 , and stimulation parameters 11, 21 .…”

Section: Introductionmentioning

confidence: 99%

Implant- and anesthesia-related factors affecting threshold intensities for vagus nerve stimulation

Ahmed

Chang

López

et al. 2021

Preprint

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Vagus nerve stimulation (VNS) is used as therapy in epilepsy and depression and is tested as a potential treatment for several chronic disorders. Typically, VNS is delivered at increasing stimulus intensity until a response is observed (threshold intensity). Factors that affect threshold intensities for engagement of different fiber types and concomitant physiological responses have not been studied. We determined neural and physiological responses to increasing stimulus intensities of VNS in anesthetized and awake animals, and examined the effect of implant- and anesthesia-related factors on threshold intensities in a rodent model of VNS. In acute and long-term cervical vagus nerve implants (53 and 14 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake at different intensities. Stimulus-evoked compound action potentials (eCAPs) were recorded, elicited physiological responses were registered, including changes heart rate (HR), breathing, and blood pressure (BP), and threshold intensities were determined. The intensity that elicits eCAPs (“neural threshold”) is significantly lower than what elicits a physiological response (“physiological threshold”, PT) (25 μA ±1.8 vs. 70 μA ±5.2, respectively; Mean ±SEM). Changes in BP occur at the lowest stimulus intensities (80 μA ±7), followed by changes in HR (105 μA ±8.4) and finally in breathing (310 μA ±32.5). PT is lower with than without electrode insulation (60 μA ±12, vs. 700 μA ±123). PT and electrode impedance are correlated in long-term (r=0.47; p<0.001) but not in acute implants (r=-0.34; p NS); both PT and impedance increase with implant age (Pearson correlation r=0.44; p<0.001 and r=0.64; p<0.001, respectively). PT is lowest when animals are awake (210 μA ±33; Mean ±SEM), followed by ketamine-xylazine (630 μA ±154), and isoflurane (1075 μA ±131). The sequence of physiological responses with increasing VNS intensity is similar in both anesthetized and awake states. Implant age, electrical impedance and the type of anesthesia affect VNS threshold and should be accounted for when determining stimulation dose.

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Characterization of Parylene-C degradation mechanisms: In vitro reactive accelerated aging model compared to multiyear in vivo implantation

Cited by 67 publications

References 62 publications

W:Ti Flexible Transversal Electrode Array for Peripheral Nerve Stimulation: A Feasibility Study

W:Ti Flexible Transversal Electrode Array for Peripheral Nerve Stimulation: A Feasibility Study

PDMS-Parylene Adhesion Improvement via Ceramic Interlayers to Strengthen the Encapsulation of Active Neural Implants

Implant- and anesthesia-related factors affecting threshold intensities for vagus nerve stimulation

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