涂覆聚氨酯材料植入神经电极的细胞相容性评价

Cytocompatibility of polyurethane-coated implanted neural electrode

背景:由于植入式电极在长期使用后会形成组织包囊,从而严重影响了电极的性能。课题组提出采用生物相容性好、离子导通能力强的聚合物涂层来包裹整个电极。这样,就能在不影响电极的电化学性能的前提下提高电极的生物相容性,使得电极在长期植入后的稳定性增强。目的:观察合成聚氨酯材料的离子导通性能以及与PC12细胞和小鼠小脑颗粒神经元的细胞相容性。设计、时间及地点:对比观察实验,于2007-10/2008-04分别在武汉大学化学院神经电极研究室和华中科技大学生科院完成。材料:首先用2,4-异佛尔酮二异氰酸酯和聚乙二醇合成预聚体,然后直接用水为交联剂,二丁基二月桂酸锡为催化剂进行交联形成聚氨酯。方法:将硅橡胶片在空气中等离子处理1min后,将一定量合成的聚氨酯溶液铺展在处理后的硅橡胶片上,形成一层均匀的薄膜。以未经涂层处理的硅橡胶片为对照。主要观察指标:采用红外测试仪对合成的聚氨酯进行官能团的分析;测试电极上涂敷聚氨酯涂层前后的循环伏安性能;观察不同材料上PC12细胞和小鼠颗粒神经元的贴附状况;计算不同材料上细胞的相对存活率。结果:红外测试说明聚乙二醇和异佛尔酮二异氰酸酯反应完全;循环伏安测试证明离子在聚氨酯膜内的导通能力较强,而且不影响电极的电化学性能;PC12细胞和小脑颗粒神经元在涂覆有聚氨酯材料的硅橡胶上的贴附状况均好于未经涂层处理的硅橡胶;MTT法实验结果表明,涂覆有聚氨酯材料的硅橡胶上细胞的存活率高于未经涂层处理的硅橡胶(P<0.001)。结论:在聚氨酯合成的过程中引入聚乙二醇,使得其不仅具有良好的离子导通性能,而且与PC12细胞和小脑颗粒神经元具有良好的细胞相容性。

BACKGROUND： A major problem which hinders the applications of neural prostheses is the inconsistent performance caused by tissue responses during long-term implantation. Therefore, polymer characterized by good biocompatibility and high ionic conductivity was used in this study to coat the electrode, aiming to improve biocompatibility and enhance stability for long-term implantation. OBJECTIVE： To investigate the ionic conductivity of synthesized polyurethane and cellular compatibility to PC12 cells and cerebellar granule neurons （CGNs）. DESIGN, TIME AND SETTING： A contrast study was performed at the Neural Electrode Research Laboratory, College of Chemistry and Molecular Science, Wuhan University, and the Life Science and Technology College of Huazhong University of Science and Technology from October 2007 to April 2008. MATERIALS： Polymer precursor was synthesized by 2,4-isophorone diisocyanate and polyethylene glycol; thereafter, water （crosslinking agent） and dibutyl tin dilaurate （catalyst） were used to form polyurethane. METHODS： Silicon rubber films were treated with plasma in the air for 1 minute, and then the synthesized polyurethane solution was evenly spread on the surface of silicon rubber films. In addition, silicon rubber films underwent no treatment were used as the controls. MAIN OUTCOME MEASURES： Functional group of synthesized polyurethane was analyzed using infrared tester; cyclic voltammetry was measured before and after coating polyurethane on the testing electrode; adhesion of PC12 cells and CGNs to different material surfaces was observed; relative survival rate of cells on different material surfaces was calculated. RESULTS： The results of the infrared test suggested that polyethylene glycol and isophorone diisocyanate （IPDI） reacted completely. The results of cyclic voltammetry showed that there was high ionic mobility within the polyurethane film and that the presence of the film did not affect the electrochemical performance of the electrodes. Adhesion and growth of PC12 and CGNs were better on polyurethane coating compared to the control material. The MTT results suggested that cell survival was significant higher on polyurethane-coated silicon rubber compared to the control material （P 〈 0.001 ）. CONCLUSION： Synthesized polyurethane with polyethylene glycol is a very promising biomedical material, which not only exhibits a high ionic conductivity, but also has good cellular compatibility with PC12 and CGNs.