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用于增强电极与神经元界面的纳米结构多孔硅的生物活性特性。

Bioactive properties of nanostructured porous silicon for enhancing electrode to neuron interfaces.

作者信息

Moxon K A, Hallman S, Aslani A, Kalkhoran N M, Lelkes P I

机构信息

Drexel, University, School of Biomedical Engineering, 3141 Chestnut Street, Philadelphia, PA 19104, USA.

出版信息

J Biomater Sci Polym Ed. 2007;18(10):1263-81. doi: 10.1163/156856207782177882.

Abstract

Many different types of microelectrodes have been developed for use as a direct brain-machine interface (BMI) to chronically recording single-neuron action potentials from ensembles of neurons. Unfortunately, the recordings from these microelectrode devices are not consistent and often last for only on the order of months. For most microelectrode types, the loss of these recordings is not due to failure of the electrodes, but most likely due to damage to surrounding tissue that results in the formation of non-conductive glial scar. Since the extracellular matrix consists of nanostructured fibrous protein assemblies, we have postulated that neurons may prefer a more complex surface structure than the smooth surface typical of thin-film microelectrodes. This porous structure could then act as a drug-delivery reservoir to deliver bioactive agents to aid in the repair or survival of cells around the microelectrode, further reducing the glial scar. We, therefore, investigated the suitability of a nanoporous silicon surface layer to increase the biocompatibility of our thin film ceramic-insulated multisite electrodes. In vitro testing demonstrated increased extension of neurites from PC12 pheochromocytoma cells on porous silicon surfaces compared to smooth silicon surfaces. Moreover, the size of the pores and the pore coverage did not interfere with this bioactive surface property, suggesting that large highly porous nanostructured surfaces can be used for drug delivery. The most porous nanoporous surfaces were then tested in vivo and found to be more biocompatible than smooth surface, producing less glial activation and allowing more neurons to remain close to the device. Collectively, these results support our hypothesis that nanoporous silicon may be an ideal material to improve biocompatibility of chronically implanted microelectrodes. The next step in this work will be to apply these surfaces to active microelectrodes, use them to deliver bioactive agents, and test that they do improve neural recordings.

摘要

人们已经开发出许多不同类型的微电极,用作直接脑机接口(BMI),以长期记录神经元群体中的单神经元动作电位。不幸的是,这些微电极设备的记录并不一致,通常仅持续数月左右。对于大多数微电极类型而言,记录的丢失并非由于电极故障,而很可能是由于周围组织受损导致形成了非导电的胶质瘢痕。由于细胞外基质由纳米结构的纤维蛋白组装体组成,我们推测神经元可能更喜欢比薄膜微电极典型的光滑表面更复杂的表面结构。这种多孔结构随后可作为药物递送库,递送生物活性剂以帮助微电极周围细胞的修复或存活,进一步减少胶质瘢痕。因此,我们研究了纳米多孔硅表面层对于提高我们的薄膜陶瓷绝缘多部位电极生物相容性的适用性。体外测试表明,与光滑硅表面相比,PC12嗜铬细胞瘤细胞在多孔硅表面上的神经突延伸增加。此外,孔的大小和孔覆盖率并未干扰这种生物活性表面特性,这表明大型高度多孔的纳米结构表面可用于药物递送。然后对孔隙率最高的纳米多孔表面进行体内测试,发现其比光滑表面具有更高的生物相容性,产生的胶质激活更少,并允许更多神经元靠近该设备。总的来说,这些结果支持了我们的假设,即纳米多孔硅可能是改善长期植入微电极生物相容性的理想材料。这项工作的下一步将是将这些表面应用于有源微电极,用它们来递送生物活性剂,并测试它们确实能改善神经记录。

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