A critical review of cell culture strategies for modelling intracortical brain implant material reactions

Gilmour, AR; Woolley, Andrew J.; Poole-Warren, Laura A.; Thomson, Christine E.; Green, Rylie A.

doi:10.1016/j.biomaterials.2016.03.011

Cited by 28 publications

(27 citation statements)

References 217 publications

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“…A primary mixed astrocyte and microglia culture from rodent cortex was used to assess material impacts on cell growth and development. These cell types were chosen as they are the most likely cell types to be in contact with these materials when applied to cortical electrode arrays as the neurons are usually displaced from the device interface . Figure shows the resulting cell coverage for both materials (Figure A) and the comparison cell morphologies observed within the culture (Figure B).…”

Section: Resultsmentioning

confidence: 99%

Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes

Goding

Gilmour

Martens

et al. 2017

Adv Healthcare Materials

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Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brain-machine interfaces. The greatest challenge to the fabrication of CH electrodes is the hybridization of dissimilar polymers (conductive polymer and hydrogel) to ensure the formation of interpenetrating polymer networks (IPN) required to achieve both soft and electroactive materials. A new hydrogel system is developed that enables tailored placement of covalently immobilized dopant groups within the hydrogel matrix. The role of immobilized dopant in the formation of CH is investigated through covalent linking of sulfonate doping groups to poly(vinyl alcohol) (PVA) macromers. These groups control the electrochemical growth of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and subsequent material properties. The effect of dopant density and interdopant spacing on the physical, electrochemical, and mechanical properties of the resultant CHs is examined. Cytocompatible PVA hydrogels with PEDOT penetration throughout the depth of the electrode are produced. Interdopant spacing is found to be the key factor in the formation of IPNs, with smaller interdopant spacing producing CH electrodes with greater charge storage capacity and lower impedance due to increased PEDOT growth throughout the network. This approach facilitates tailorable, high-performance CH electrodes for next generation, low impedance neuroprosthetic devices.

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Section: Resultsmentioning

confidence: 99%

Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes

Goding

Gilmour

Martens

et al. 2017

Adv Healthcare Materials

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show abstract

“…This progression of modulus loss over time is well aligned with the implant and neural recovery period. [3,4] It is known that an implant requires a modulus higher than that of the neural tissue to facilitate an accurate and low damage insertion; however, the ongoing presence of stiff materials will impart a frustrated immune response and hence generate scar tissue. [3] It should be noted that the living electrode construct is not designed to be implanted on the day it is fabricated.…”

Section: Resultsmentioning

confidence: 99%

“…[1,2] The consequences of this mode of operation is that chronic frustration of the wound-healing process produces a scar tissue reaction, which encapsulates the implant and electrically isolates it from the target tissue. [3,4] As a result, the amount of charge required to activate the target tissue often increases over time and the implant loses efficacy. [5,6] Rather than relying on unwieldy metal electrodes and direct charge injection, tissue-engineered bioelectronics will use cells embedded within devices to provide a natural mode of physiologic tissue activation.…”

Section: Introductionmentioning

confidence: 99%

A living electrode construct for incorporation of cells into bionic devices

et al. 2017

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A living electrode construct that enables integration of cells within bionic devices has been developed. The layered construct uses a combination of non-degradable conductive hydrogel and degradable biosynthetic hydrogel to support cell encapsulation at device surfaces. In this study, the material system is designed and analyzed to understand the impact of the cell carrying component on electrode characteristics. The cell carrying layer is shown to provide a soft interface that supports extracellular matrix development within the electrode while not significantly reducing the charge transfer characteristics. The living layer was shown to degrade over 21 days with minimal swelling upon implantation.

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“…[2] MEAs provide a noninvasive way to record changes in the extracellular field generated by cells cultured on the device. The field potentials are caused by ionic current flow within the cell culture Overall, a total recording yield of 21.4% is achieved, with more than 90% obtained from electrodes with neurospheres, maximizing the functionality of these planar MEAs as effective tools to study pharmacology-based effects on neural networks.…”

Section: Introductionmentioning

confidence: 99%

“…[6] Since then, this in vitro method has been widely explored, and a diverse catalogue of MEAs has been developed for different applications. [2,4,5] Essential for in vitro recording are: (1) an accurate and sensitive recording system and (2) an electrically active neural network. To this end, various device designs and neural cell culture optimizations have been explored to improve the success of microelectrode studies, as briefly described below.…”

Section: Introductionmentioning

confidence: 99%

Neurospheres on Patterned PEDOT:PSS Microelectrode Arrays Enhance Electrophysiology Recordings

et al. 2017

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Microelectrode arrays (MEAs) are a versatile diagnostic tool to study neural networks. Culture of primary neurons on these platforms allows for extracellular recordings of action potentials. Despite many advances made in the technology to improve such recordings, the recording yield on MEAs remains sparse. Here, enhanced recording yield is shown induced by varying cell densities on poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate)‐coated MEAs. It is demonstrated that high cell densities (900 cells mm−2) of primary cortical cells increase the number of recording electrodes by 53.1% ± 11.3%, compared with low cell densities (500 cells mm−2) with 6.3% ± 1.4%. To further improve performance, 3D clusters known as neurospheres are cultured on the MEAs, significantly increasing single unit activity recordings. Extensive spike sorting is performed to analyze the unit activity recording multiple neurons with a single microelectrode. Finally, patterning of polyethylene glycol diacrylate through laser ablation is demonstrated, as a means to more precisely confine neurospheres on top of the electrodes. The possibility of recording single neurons with multiple neighboring electrodes is shown. Overall, a total recording yield of 21.4% is achieved, with more than 90% obtained from electrodes with neurospheres, maximizing the functionality of these planar MEAs as effective tools to study pharmacology‐based effects on neural networks.

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A critical review of cell culture strategies for modelling intracortical brain implant material reactions

Cited by 28 publications

References 217 publications

Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes

Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes

A living electrode construct for incorporation of cells into bionic devices

Neurospheres on Patterned PEDOT:PSS Microelectrode Arrays Enhance Electrophysiology Recordings

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