| Therapies of electrical stimulation based on neural prostheses provide the novel and effective methods for the treatment of neural diseases such as stroke, epilepsy, Parkinson’s disease etc. Currently we are in a key stage for developing various of neural electrical stimulators towards the clinic application. As the important components of neural electrical stimulator, neural electrodes play an important role because it contacts with neural tissue directly and injects the stimulation charge into target neural tissue. There are two major scientific problems in developing neural electrodes, which are the electrochemical performance and inflammatory response caused by the implanted electrodes.In order to improve the stability of the performance, the electrochemical and biocompatible modifications were investigated to solve the two problems in this study. The detailed contents are as follows.The section1including chapter2,3,4is the section of electrochemical modification for neural electrode. Chapter2presents the experiment that iridium oxides was electrodeposited on the microelectrode array (MEA) used for the visual prostheses to improve its electrochemical performance. The experimental results showed the electrochemical performance in the phosphate buffered solution (PBS) was improved remarkably. The impedance of electrode at1kHz decreased by32%after electrodeposition, the safe charge injection (Qinj) limit increased from0.11mC/cm2to2.5mC/cm2. The results indicate that the electrodeposition technique can be adopted to improve the electrochemical performance of MEA made through Micro-electromechanical Systems (MEMS).In chapter3, the Multi-Walled Carbon Nanotubes (MWCNT) doped Poly(3,4-ethylenedioxythiophene)(PEDOT) was used to modified the Pt electrodes. The different modes of electrodeposition were performed and the electrochemical performance of composite films deposited with different modes were compared. The results showed galvanostatically polymerized PEDOT/MWCNT films possessed superior electrochemical characteristics and stability compared to the films fabricated with potentiostatic polymerization, and the Qinj limit reached6.2mC/cm2for cathodic-first pulses. Cell assay revealed PEDOT/MWCNT films could promote the adhesion and neurite outgrowth of rat pheochromocytoma cells. Platinum wires coated with PEDOT/MWCNT films were implanted into rats’cortex for6weeks for histological evaluation. Glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) staining revealed that the PEDOT/MWCNT implants elicit lower tissue response compared to the platinum implants within the150μm (p<0.05). Based on the superior characteristic above, we consider the PEDOT/MWCNT films deposited in the optimized condition is suitable as the materials of neural electrode with high Qinj limit for the long-term implantation.The chapter4, we studied the electrodeposition of Graphene (Gr) doped PEDOT to modify the Pt electrodes. The different modes and parameter of deposition were investigated, the results showed potentiostatically deposited PEDOT/Gr films with2.4mC/cm2deposition charge passing possessed the best electrochemical performance. And the PEDOT/Gr films deposited in this condition showed the better electrochemical performance and stability compared to the galvanostatically polymerized PEDOT/MWCNT films in the last chapter. The Qinj limit reached10.7mC/cm2for cathodic-first pulses. In addition, the PEDOT/Gr films showed the good biocompatibility in the differentiation experiment of neural stem cell. The PEDOT/Gr films display the great potential in the application of visual prostheses.The section2including chapter5,6is the section of biocompatible modification for neural electrode. In chapter5, implantable silicon rubber hat microelectrodes were coated with the poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PVA/PAA IPNs) hydrogel films and were implanted into the motor cortex of rats for28days. The impedance of microelectrodes was monitored weekly, and results indicated the impedance of EIROF microelectrodes with coatings reduced by-40%compared to the EIROF microelectrodes without coatings at day21post-implantation, so PVA/PAA hydrogel film coatings could stabilize the property of electrical charge transfer on the EIROF microoelectrode-tissue interface The study demonstrates a concept of neural microelectrode modification, in which the hydrophilic film coating is crucial.In Chapter6, we investigated the method of covalent graft to improve the biocompatibility of Poly (dimethylsiloxane)(PDMS). Firstly, PDMS was treated with plasma to introduce active groups, subsequently the different molecular weight polyethylene glycol (PEG) and the poly-L-lysine (PLL) were grafted on the surface of PDMS film. The cytocompatibility of materials before and after graft were assessed quantitatively by the adhesion and differentiation of PC12cells on the surface of materials. The results indicated PEG600grafted PDMS possessed the best hydrophilicity and cytocompatibility. This study did not only improve the biocompatibility of PDMS, but also provided a convenient screening method for the preliminary assessment of materials biocompatibility using PC12cells.The section3is the chapter7, a novel cellular electrical stimulation device based on ITO conducting glass was fabricated with the MEMS technology. The device has some very tiny stimulation sites like the MEA and it can deliver current pulses in the culture medium to excite the neural stem cells. We hope the electrical stimulation through the device could improve the differentiation of neural stem cells towards neurons. Because it is a preliminary tentative experiment, the results did not show a significant difference in the differentiation of neural stem cells between the stimulation group and non-stimulation group. This was probably due to the improper stimulation parameter or other factors. In the future work, we will further develop the device, including device fabrication, stimulation parameters, and other possible influencing factors. |
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