Nanostructured Coatings for Improved Charge Delivery to Neurons

Frontiers in Neuroengineering, 2014

ACS Applied Bio Materials, 2019

Intracortical microelectrode arrays (MEAs) are a valuable tool for neuroscience research, and their potential clinical use has been demonstrated. However, their inability to function reliably over chronic timepoints has limited their clinical translation. MEA failure is highly correlated with the foreign body response (FBR) and therapeutics have been used to reduce the FBR and improve device function, with drugs such as minocycline showing promising results in vivo. To avoid issues associated with systemic drug delivery, device coatings can be used to for therapeutic delivery. One method to locally deliver minocycline is a layer-by-layer (LBL) coating that consists of multiple trilayers of gelatin type A, minocycline, and dextran sulfate; however, the coating’s impact on device function was previously unknown. This work characterized 10, 20, and 30 trilayer coatings then evaluated their effect on device function. Cumulative minocycline release and coating thickness increased with the number of trilayers, agreeing with observations in previous studies. Atomic force microscopy images were used to calculate surface roughness of the coatings, which significantly increased from 10 to 20 trilayers, then remained relatively constant upon increasing to 30 trilayers. Scanning electron microscopy images confirmed trilayers coated the MEAs. Electrochemical impedance spectroscopy (EIS) and charge carrying capacity (CCC), were used to evaluate the coating’s effect on MEA electrochemical behavior over 3 weeks while the coated MEAs soaked in PBS. The 10 trilayer coatings slightly decreased CCC, while 20 and 30 trilayers initially increased CCC. CCC of all trilayers gradually increased as the MEAs soaked in PBS. All trilayers initially increased MEA impedance magnitude and reduced the phase angle at low frequencies. Impedance magnitude at 1 kHz and 15 kHz decreased towards their initial precoated values for all trilayers as the MEAs soaked in PBS. Overall, these results show that the LBL coatings did not significantly impact MEA function.

Proceedings, 2017

This study introduces two new processes that highly enable PEDOT:PSS (poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)) as stable coating material for chronic neural stimulation. In first process, strong mechanical bonding between PEDOT:PSS coating and gold electrodes is achieved by creating rough porous surface with partial iodine etching. PEDOT:PSS coating on iodine etched gold electrode shows 100% stability under strong ultrasonic treatment. The second process represents electrochemical modification of PEDOT:PSS coating by cyclic voltammetry method in Ringer's solution. This process reduces electrode polarization 33% during stimulation. Therefore, charge injection capacity increases that ensures safe stimulation. A combination of both processes facilitates the use of PEDOT:PSS coating for successful chronic neural recording and stimulation.

ACS Nano, 2013

The ongoing interest in densely packed miniaturized electrode arrays for high-resolution epicortical recordings has induced many researchers to explore the use of nanomaterial coatings to reduce electrode impedance while increasing signalto-noise ratio and charge injection capability. Although these materials are very effective, their use in clinical practice is strongly inhibited by concerns about the potential risks derived from the use of nanomaterials in direct contact with the human brain. In this work we propose a novel approach to safely couple nanocoated electrodes to the brain surface by encapsulating them with a biocompatible hydrogel. We prove that fibrin hydrogel coating over nanocoated high-density arrays of epicortical microelectrodes is electrically transparent and allows avoiding direct exposure of the brain tissue to the nanocoatings while maintaining all the advantages derived from the nanostructured electrode surface. This method may make available acute and sub-acute neural recordings with nanocoated high-resolution arrays for clinical applications.

Electrostimulation of the neural system in functional or repair therapies requires new materials that protect the living system from electric field (EF) effects at the interface. Intercalation materials offer an alternative to radical formation during stimulation. Furthermore, nanostructuring of the electroactive material used as electrode offers an enlargement of the charge capacity which in turn involves changes in the EF effect. In this work, electric field stimulation of cortical neuron cultures has been applied in an in vitro model of lesion, namely, a physical scratch in the cell culture creates a cell-free area reminiscent of a lesion where new neurites grow. Regeneration of the "wound" zone upon EF stimulation is observed for various types of electrode materials, and compared to the spontaneous process and to platinum electrodes. Significantly, electric field effects are highly dependent on the electrode material used, even for the same charge delivered and similar impedance values. Electrode coatings with large charge storage capacity yield significantly better results than that of bare Pt electrodes. Neurite outgrowth at the scratched "wound" zone is lowest, below spontaneous regeneration, when using Pt electrodes. On the other hand, electroactive materials, such as bilayers of PEDOT and polypyrrole with lysine counterions or iridium oxide-pristine graphene hybrids, promote further regeneration. Beyond impedance considerations, the optimal material is the nanostructured one with the largest charge capacity, even at low charge deliveries. It is remarkable that IrOx-graphene hybrids reach regenerations above spontaneous case in very short stimulation times, for equal charge deliveries and potential protocols. The implications from the results suggest that EF application using these new coatings, may have an immediate use in safer electrostimulation procedures, and open routes for much needed neural repair.

2015

Neural electrodes hold tremendous potential for improving understanding of brain function and restoring lost neurological functions. Multi-walled carbon nanotube (MWCNT) and dexamethasone (Dex)-doped poly(3,4-ethylenedioxythiophene) (PEDOT) coatings have shown promise to improve chronic neural electrode performance. Here, we employ electrochemical techniques to characterize the coating in vivo. Coated and uncoated electrode arrays were implanted into rat visual cortex and subjected to daily cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) for 11 days. Coated electrodes experienced a significant decrease in 1 kHz impedance within the first two days of implantation followed by an increase between days 4 and 7. Equivalent circuit analysis showed that the impedance increase is the result of surface capacitance reduction, likely due to protein and cellular processes encapsulating the porous coating. Coating’s charge storage capacity remained consistently higher than uncoated electrodes, demonstrating its in vivo electrochemical stability. To decouple the PEDOT/MWCNT material property changes from the tissue response, in vitro characterization was conducted by soaking the coated electrodes in PBS for 11 days. Some coated electrodes exhibited steady impedance while others exhibiting large increases associated with large decreases in charge storage capacity suggesting delamination in PBS. This was not observed in vivo, as scanning electron microscopy of explants verified the integrity of the coating with no sign of delamination or cracking. Despite the impedance increase, coated electrodes successfully recorded neural activity throughout the implantation period.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2007

Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least 1 week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albuminreleasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuronelectrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function.

Advanced Functional Materials, 2009

Advanced Materials

This review focuses on the application of nanomaterials for neural interfacing. The junction between nanotechnology and neural tissues can be particularly worthy of scientific attention for several reasons: (i) Neural cells are electroactive, and the electronic properties of nanostructures can be tailored to match the charge transport requirements of electrical cellular interfacing. (ii) The unique mechanical and chemical properties of nanomaterials are critical for integration with neural tissue as long-term implants. (iii) Solutions to many critical problems in neural biology/medicine are limited by the availability of specialized materials. (iv) Neuronal stimulation is needed for a variety of common and severe health problems. This confluence of need, accumulated expertise, and potential impact on the well-being of people suggests the potential of nanomaterials to revolutionize the field of neural interfacing. In this review, we begin with foundational topics, such as the current status of neural electrode (NE) technology, the key challenges facing the practical utilization of NEs, and the potential advantages of nanostructures as components of chronic implants. After that the detailed account of toxicology and biocompatibility of nanomaterials in respect to neural tissues is given. Next, we cover a variety of specific applications of nanoengineered devices, including drug delivery, imaging, topographic patterning, electrode design, nanoscale transistors for high-resolution neural interfacing, and photoactivated interfaces. We also critically evaluate the specific properties of particular nanomaterials-including nanoparticles, nanowires, and carbon nanotubes-that can be taken advantage of in neuroprosthetic devices. The most promising future areas of research and practical device engineering are discussed as a conclusion to the review. Hyman Professor of Chemistry, and the School of Engineering and Applied Sciences. At Harvard, Lieber has pioneered the synthesis of a broad range of nanoscale materials, the characterization of the unique physical properties of these materials and the development of methods of hierarchical assembly of nanoscale wires, together with the demonstration of applications of these materials in nanoelectronics, nanocomputing, biological and chemical sensing, neurobiology, and nanophotonics. Lieber has also developed and applied a new chemically sensitive microscopy for probing organic and biological materials at nanometer and molecular scales.

2015

Objective. The dorsal root ganglion is an attractive target for implanting neural electrode arrays that restore sensory function or provide therapy via stimulation. However, penetrating microelectrodes designed for these applications are small and deliver low currents. For long-term performance of microstimulation devices, novel coating materials are needed in part to decrease impedance values at the electrode-tissue interface and to increase charge storage capacity. Approach. Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall carbon nanotubes (CNTs) were coated on the electrode surface and doped with the anti-inflammatory drug, dexamethasone. Electrode characteristics and the tissue reaction around neural electrodes as a result of stimulation, coating and drug release were characterized. Hematoxylin and eosin staining along with antibodies recognizing Iba1 (microglia/macrophages), NF200 (neuronal axons), NeuN (neurons), vimentin (fibroblasts), caspase-3 (cell death) and L1 (neural cell adhesion molecule) were used. Quantitative image analyses were performed using MATLAB. Main results. Our results indicate that coated microelectrodes have lower in vitro and in vivo impedance values. Significantly less neuronal death/damage was observed with coated electrodes as compared to non-coated controls. The inflammatory response with the PEDOT/CNT-coated electrodes was also reduced. Significance. This study is the first to report on the utility of these coatings in stimulation applications. Our results indicate PEDOT/CNT coatings may be valuable additions to implantable electrodes used as therapeutic modalities.