Basic Investigation On The Applications Of Implantable Neural Stimulation Device

Part1Background and objective:The instability of the interface between chronically implanted neural electrodes and neural tissue is a major obstacle to their long-term use in clinical practice. In this study, we investigate the feasibility of polyethylene glycol (PEG)-containing polyurethane (PU) hydrogel as coatings for polydimethylsiloxane (PDMS) based neural electrodes in order to achieve a stable neural interface.Methods:PU hydrogel was synthesized with different molecular weights of PEG (400,600,1000). The swelling ratio and bulk ionic conductivity of hydrogel films were measured to determine the most suitable one to conduct further investigation. The influence of PU hydrogel film coatings on electrode electrochemical behaviour was determined. The surface properties of PU films were characterized by water contact angle and protein adsorption measurements. The PDMS substrate was activated with water plasma and coated with the PU hydrogel coating. PC12cells were cultured on PU coated PDMS films and control PDMS films. And finally, PDMS implants with (n=10) and without (n=8) PU coatings were implanted into the cortex of rats and the tissue response to the implants was evaluated six weeks post implantation by the expression of GFAP and NeuN.Results:The PU synthesized using PEG1000was chosen as the best candidate coating material for further study. Changes in the electrochemical impedance of microelectrodes with PU coatings were negligible. The amount of protein adsorption on the PDMS substrate was reduced by93%after coating. PC12cells exhibited more and longer neurites on PU films than on PDMS substrates. Furthermore, GFAP staining for astrocytes and NeuN staining for neurons revealed that PU coatings attenuated glial scarring and reduced the neuronal cell loss around the implants.Conclusion:PU hydrogel coating can improve the biocompatibility of PDMS based neural electrodes and is favourable for neural electrode applications. Part2Objective:To investigate the effect of electrical stimulation on the differentiation of neural stem cells, we design a new type of cell stimulation device and evaluate its safety and efficacy and observe the effect of electrical stimulation on the differentiation of neural stem cells.Methods:PC12cells were seeded in the bottom of the device. After6h starvation, electrical stimulation was initiated with the current intensity of2.8mA for5days. The cells were stained with the β-Ⅲ-tubulin antibody to observe the cell viability and the neurite outgrowth. Neural stem cells seeded in the bottom of the device were stimulated with the same electrical current intensity, and then stained with the β-Ⅲ-tubulin and GFAP antibody to observe the effect of electrical stimulation on differentiation of neural stem cell.Results:After5days of stimulation, the number of PC12cells in the stimulation group was lower than that of the control group, but the neurite length of PC12cells in the stimulation group was longer than that of the control group. The neural stem cells treated with the same electrical current intensity differentiated less neurons compared with the control group. And the effect of electrical stimulation on the differentiation of neural stem cells was not obvious after we adjust the electrical stimulation parameters.Conclusion:This electrical stimulation device is effective in promoting the neurite outgrowth of PC12cells and neurons are more sensitive to electrical stimulation than PC12cells. And the effect of electrical stimulation on the differentiation of neural stem cells was not obvious. This may be due to the presence of fetal bovine serum. This electrical stimulation device can be used to further investigate the effect of different simulation patterns and intensity on the differentiation of neural stem cells.