The development of neural stimulators: a review of preclinical safety and efficacy studies

Shepherd, Robert K.; Villalobos, Joel; Burns, Owen; Nayagam, David A. X.

doi:10.1088/1741-2552/aac43c

Cited by 53 publications

(52 citation statements)

References 253 publications

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“…In medical technology, design, manufacturing and function of new implants must abide by strict compliance regulations to ensure patient safety and good clinical practice. [ 13 ] This engineering task is until now mainly taken up by actors from the medtech industry. However, the introduction of bioinspired and biomimetic materials, form factors, and functionality enabled by micro‐ and nanotechnology, calls for novel insights and validation methods before industrialization.…”

Section: Figurementioning

confidence: 99%

Soft, Implantable Bioelectronic Interfaces for Translational Research

et al. 2020

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The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab‐based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e‐dura. Anatomy, implant function, and surgical procedure guide the system design. A high‐yield, silicone‐on‐silicon wafer process is developed to ensure reproducible characteristics of the electrodes. A biomimetic multimodal platform that replicates surgical insertion in an anatomy‐based model applies physiological movement, emulates therapeutic use of the electrodes, and enables advanced validation and rapid optimization in vitro of the implants. Functionality of scaled e‐dura is confirmed in nonhuman primates, where epidural neuromodulation of the spinal cord activates selective groups of muscles in the upper limbs with unmet precision. Performance stability is controlled over 6 weeks in vivo. The synergistic steps of design, fabrication, and biomimetic in vitro validation and in vivo evaluation in translational animal models are of general applicability and answer needs in multiple bioelectronic designs and medical technologies.

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Section: Figurementioning

confidence: 99%

Soft, Implantable Bioelectronic Interfaces for Translational Research

et al. 2020

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“…Large animals such as cats, dogs, sheep, pigs, and non-human primates, are used for chronic studies on the efficacy and safety of neural stimulators. They concern the analysis of both biotic and abiotic reactions on the tissue-electrode interface in long-term experiments (Shepherd et al, 2018). The employment of large animals for these types of investigations is recommended because their anatomy perfectly mimics the environment in which microelectrodes will be applied, allowing the use of all the device components in their real size.…”

Section: Experimental Models To Study Foreign Body Response To Neuralmentioning

confidence: 99%

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes

et al. 2019

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The development of implantable neuroelectrodes is advancing rapidly as these tools are becoming increasingly ubiquitous in clinical practice, especially for the treatment of traumatic and neurodegenerative disorders. Electrodes have been exploited in a wide number of neural interface devices, such as deep brain stimulation, which is one of the most successful therapies with proven efficacy in the treatment of diseases like Parkinson or epilepsy. However, one of the main caveats related to the clinical application of electrodes is the nervous tissue response at the injury site, characterized by a cascade of inflammatory events, which culminate in chronic inflammation, and, in turn, result in the failure of the implant over extended periods of time. To overcome current limitations of the most widespread macroelectrode based systems, new design strategies and the development of innovative materials with superior biocompatibility characteristics are currently being investigated. This review describes the current state of the art of in vitro, ex vivo , and in vivo models available for the study of neural tissue response to implantable microelectrodes. We particularly highlight new models with increased complexity that closely mimic in vivo scenarios and that can serve as promising alternatives to animal studies for investigation of microelectrodes in neural tissues. Additionally, we also express our view on the impact of the progress in the field of neural tissue engineering on neural implant research.

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“…With their stable and unique physical properties, many polymeric materials, including SU-8 (Altuna et al, 2010 ), polyimide (Bakonyi et al, 2013 ), Parylene (Ceyssens and Puers, 2015 ), polydimethylsiloxane (PDMS), and liquid crystal polymers (LCPs) (Hwang et al, 2013 ), have been widely used as packaging materials for neural recording electrodes. The design consideration of neural stimulation electrodes is similar to that of neural recording electrodes, concerning biocompatibility, mechanical properties, electrical properties, and stability (Shepherd et al, 2018 ). For example, platinum black and Ir/IrOx are also widely used as stimulating electrodes (Zhang et al, 2015 ; Chen et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Neural stimulators also have the same strict requirements on hermeticity, long-term stability, and biocompatibility of device package (Vanhoestenberghe and Donaldson, 2013 ; Donaldson and Brindley, 2016 ). Many materials that have been utilized in neural stimulating probes include but are not limited to: ceramics, glass, epoxy, silicone, and so on (Amanat et al, 2010 ; Vanhoestenberghe and Donaldson, 2013 ; Shepherd et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

A Review: Electrode and Packaging Materials for Neurophysiology Recording Implants

Yang

Gong

2021

Front. Bioeng. Biotechnol.

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To date, a wide variety of neural tissue implants have been developed for neurophysiology recording from living tissues. An ideal neural implant should minimize the damage to the tissue and perform reliably and accurately for long periods of time. Therefore, the materials utilized to fabricate the neural recording implants become a critical factor. The materials of these devices could be classified into two broad categories: electrode materials as well as packaging and substrate materials. In this review, inorganic (metals and semiconductors), organic (conducting polymers), and carbon-based (graphene and carbon nanostructures) electrode materials are reviewed individually in terms of various neural recording devices that are reported in recent years. Properties of these materials, including electrical properties, mechanical properties, stability, biodegradability/bioresorbability, biocompatibility, and optical properties, and their critical importance to neural recording quality and device capabilities, are discussed. For the packaging and substrate materials, different material properties are desired for the chronic implantation of devices in the complex environment of the body, such as biocompatibility and moisture and gas hermeticity. This review summarizes common solid and soft packaging materials used in a variety of neural interface electrode designs, as well as their packaging performances. Besides, several biopolymers typically applied over the electrode package to reinforce the mechanical rigidity of devices during insertion, or to reduce the immune response and inflammation at the device-tissue interfaces are highlighted. Finally, a benchmark analysis of the discussed materials and an outlook of the future research trends are concluded.

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The development of neural stimulators: a review of preclinical safety and efficacy studies

Cited by 53 publications

References 253 publications

Soft, Implantable Bioelectronic Interfaces for Translational Research

Soft, Implantable Bioelectronic Interfaces for Translational Research

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes

A Review: Electrode and Packaging Materials for Neurophysiology Recording Implants

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