Bioactive Conducting Hydrogels for Neural Interfacing Electrodes

Conducting polymer (CP) electrodes are a promising alternative to metallic electrodes, demonstrating superior electrochemical charge transfer within biological systems. However, the benefit of CPs in vitro has not been realised in vivo due to persistence of the foreign body response. One approach to overcoming this limitation is the incorporation of bioactive factors within CPs to mitigate the inflammatory response. However, incorporation of large biomolecules significantly degrades the mechanical stability of CPs.This thesis investigated the incorporation of small bioactive factors in the CP poly(3,4-ethylene dioxythiophene) (PEDOT). It was hypothesised that smaller biomolecules may preserve CP mechanical properties. The bioactive molecules dexamethasone phosphate (DP), a powerful anti-inflammatory drug, and valproic acid (VA), an anti-inflammatory and neuroprotective agent, were investigated as bioactive dopants for PEDOT. The resulting physico-mechanical, electrochemical and biological properties were assessed. Bioactive PEDOT was found to maintain the beneficial electrochemical properties of CPs while being capable of significant attenuation of inflammation in vitro. Despite using smaller bioactive factors, the mechanical robustness of the CP was compromised, making them an unsuitable solution. To address mechanical limitations, a conducting hydrogel (CH) was developed consisting of PEDOT grown within poly(vinyl alcohol) (PVA). CHs combine the mechanical properties of hydrogels with the electrical functionality of CPs. The formation of interpenetrating networks (IPN) of the two polymer components is essential to the fabrication of optimal CHs. To promote IPNs, PVA was chemically modified to incorporate covalently linked taurine doping molecules, designed to increase interaction between the polymer networks. The impact of taurine density and distribution within the PVA, was characterised both for the homogenous hydrogel and the resultant CH following growth of PEDOT within the PVA. IPN formation was examined through the physical, mechanical and electrochemical properties of the PEDOT/PVA-taurine. It was found that inter-dopant spacing along the PVA was critical to controlling growth of CP throughout the hydrogel. Smaller inter-dopant spacing encouraged the formation of IPNs.Finally, DP and VA were incorporated within PEDOT/PVA CHs. Coatings maintained their hydrogel-like mechanical properties and the incorporated molecules exhibited bioactivity. Future work will focus on the impact of CH biofunctionalisation on the in vivo inflammatory response

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

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

Stimulation of peripheral nerves using conductive hydrogel electrodes

Nerve block via electrical stimulation of nerves requires a device capable of transferring large amounts of charge across the neural interface on chronic time scales. Current metal electrode designs are limited in their ability to safely and effectively deliver this charge in a stable manner. Conductive hydrogel (CH) coatings are a promising alternative to metal electrodes for neural interfacing devices. This study assessed the performance of CH electrodes compared to platinum-iridium (PtIr) electrodes in commercial nerve cuff devices in both the in vitro and acute in vivo environments. CH electrodes were found to have higher charge storage capacities and lower impedances compared to bare PtIr electrodes. Application of CH coatings also resulted in a three-fold increase in in vivo charge injection limit. These significant improvements in electrochemical properties will allow for the design of smaller and safer stimulating devices for nerve block applications

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

Afamelanotide for erythropoietic protoporphyria

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