Josef Goding

Conductive Hydrogels: Mechanically Robust Hybrids for Use as Biomaterials

A hybrid system for producing conducting polymers within a doping hydrogel mesh is presented. These conductive hydrogels demonstrate comparable electroactivity to conventional conducting polymers without requiring the need for mobile doping ions which are typically used in literature. These hybrids have superior mechanical stability and a modulus significantly closer to neural tissue than materials which are commonly used for medical electrodes. Additionally they are shown to support the attachment and differentiation of neural like cells, with improved interaction when compared to homogeneous hydrogels. The system provides flexibility such that biologic incorporation can be tailored for application.

Small bioactive molecules as dual functional co-dopants for conducting polymers

Biological responses to neural interfacing electrodes can be modulated via biofunctionalisation of conducting polymer (CP) coatings. This study investigated the use of small bioactive molecules with anti-inflammatory properties. Specifically, anionic dexamethasone phosphate (DP) and valproic acid (VA) were used to dope the CP poly(ethylenedioxythiophene) (PEDOT). The impact of DP and VA on material properties was explored both individually and together as a codoped system, compared to the conventional dopant p-toluenesulfonate (pTS). Electrical properties of DP and VA doped PEDOT were reduced in comparison to PEDOT/pTS, however co-doping with both DP and VA was shown to significantly improve the electroactivity of PEDOT in comparison the individually doped coatings. Similarly, while the individually doped PEDOT coatings were mechanically friable, the inclusion of both dopants during electropolymerisation was shown to attenuate this response. In a whole-blood model of inflammation all DP and VA doped CPs retained their bioactivity, causing a significant reduction in levels of the pro-inflammatory cytokine TNF-α. These studies demonstrated that small charged bioactive molecules are able act as dopants for CPs and that co-doping with ions of varied size and doping affinity may provide a means of addressing the limitations of large bulky bimolecular dopants.

Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes

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.

Electrochemical stability of poly(ethylene dioxythiophene) electrodes

The conducting polymer poly(ethylene dioxythiopene) (PEDOT) has been investigated as a coating for visual prosthesis electrode arrays. The prototype electrode array was coated with PEDOT doped with two conventional anions: paratoluene sulfonate (pTS) and lithium perchlorate (LiClO4). PEDOT variants were analyzed for charge injection limit, electrochemical stability following continuous biphasic stimulation, accelerated ageing and steam sterilization conditions. It was found that PEDOT/LiClO4 was the most stable conducting polymer under chronic stimulation and high temperature circumstances. However, PEDOT/pTS exhibited acceptable stability in comparison to conventional platinum.

Conductive Hydrogel Electrodes for Delivery of Long-Term High Frequency Pulses

Nerve block waveforms require the passage of large amounts of electrical energy at the neural interface for extended periods of time. It is desirable that such waveforms be applied chronically, consistent with the treatment of protracted immune conditions, however current metal electrode technologies are limited in their capacity to safely deliver ongoing stable blocking waveforms. Conductive hydrogel (CH) electrode coatings have been shown to improve the performance of conventional bionic devices, which use considerably lower amounts of energy than conventional metal electrodes to replace or augment sensory neuron function. In this study the application of CH materials was explored, using both a commercially available platinum iridium (PtIr) cuff electrode array and a novel low-cost stainless steel (SS) electrode array. The CH was able to significantly increase the electrochemical performance of both array types. The SS electrode coated with the CH was shown to be stable under continuous delivery of 2 mA square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a beneficial electrode material compatible with long-term delivery of high current, high energy waveforms.

Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to Restore Vision

The bypassing of degenerated photoreceptors using retinal neurostimulators is helping the blind to recover functional vision. Researchers are investigating new ways to improve visual percepts elicited by these means as the vision produced by these early devices remain rudimentary. However, several factors are hampering the progression of bionic technologies: the charge injection limits of metallic electrodes, the mechanical mismatch between excitable tissue and the stimulating elements, neural and electric crosstalk, the physical size of the implanted devices, and the inability to selectively activate different types of retinal neurons. Electrochemical and mechanical limitations are being addressed by the application of electromaterials such as conducting polymers, carbon nanotubes and nanocrystalline diamonds, among other biomaterials, to electrical neuromodulation. In addition, the use of synthetic hydrogels and cell-laden biomaterials is promising better interfaces, as it opens a door to establishing synaptic connections between the electrode material and the excitable cells. Finally, new electrostimulation approaches relying on the use of high-frequency stimulation and field overlapping techniques are being developed to better replicate the neural code of the retina. All these elements combined will bring bionic vision beyond its present state and into the realm of a viable, mainstream therapy for vision loss.

In vitro biological assessment of electrode materials for neural interfaces

The development of the next generation electrode interfaces for neural prosthetic devices requires high-through-put multifaceted testing strategies to assess material interactions with both peripheral and central nervous system (CNS) immune cells. The utility of a primary astrocyte enriched glial cell culture was assessed as a potential in vitro tool for understanding the immune response to electrode materials. Conductive polymer consisting of electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) doped with paratoluene sulfonate (pTS) was used as a novel electrode material and compared to the conventional electrode material, platinum (Pt). Morphology of astrocytes and microglia in contact with the materials was analyzed and compared to an immunoassay of TNFα release from human blood plasma. While all electrode materials failed to stimulate TNFα release from human leukocytes, the materials in contact with glial cells resulted in progressive reactive gliosis. This primary astrocyte in vitro assay provides insight into the degeneration of electrode performance in vivo as a result of scar tissue reactions in chronic implant devices. It also highlights the relevance of testing for immune reactions with an appropriate cell system.

Biosynthetic conductive polymer composites for tissue-engineering biomedical devices

Conductive composites based on conductive polymers (CPs) have enabled the development of a range of materials for biomedical applications that can be tailored to improve material properties critical to long-term performance of implantable devices. Nonconductive polymers can be used to impart tailored presentation of biomolecules and improve the brittle mechanical properties of CPs. Additionally, CPs have been used to successfully impart conductivity to hydrogel and elastomeric polymers. While there have been significant challenges in producing interpenetrating networks of CPs, several approaches have yielded materials with bulk characteristics that indicate the presence of each of the component polymers. True interpenetrating networks (IPNs), such as double networks, where one network is a CP have not yet been realised; however, it is expected that IPNs will provide optimal materials with the highest electroactivity.

CHAPTER 8:Bioactive Conducting Polymers for Optimising the Neural Interface

Increasing demands on neuroprosthetic bioelectrodes have created a need for electrode materials that can support the safe and sustainable delivery of electrical stimulation to excitable tissues. Conducting polymers have become a focal point of research into next-generation electrode materials due to their superior electrical properties for charge transfer in biological environments. Perhaps the greatest potential of conducting polymers within neural applications is their ability to accommodate biofunctionality through the incorporation and controlled release of bioactive molecules. Incorporation of neurotrophic factors, cell adhesion molecules and various drug compounds within conducting polymers has been shown to assist in the development of higher quality tissue–electrode interfaces. However, limitations associated with drug loading and the impact of adding biological molecules on mechanical and electrical properties of biofunctionalised conducting polymers restrict their use in medical device applications. This chapter assesses the role of conducting polymers as bioelectrode materials, means of biofunctionalisation and the resultant challenges and limitations. Furthermore, this chapter evaluates the strategies developed to overcome these limitations in the pursuit of the development of high quality neural interfaces.