Winter Jessica O, Cogan Stuart F, Rizzo Joseph F
Center for Innovative Visual Rehabilitation, Boston VA Hospital, Boston, Massachusetts, USA.
J Biomed Mater Res B Appl Biomater. 2007 May;81(2):551-63. doi: 10.1002/jbm.b.30696.
Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least 1 week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albumin-releasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuron-electrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function.
用于中枢神经系统的改进型感觉和运动假体将需要大量对神经兴奋具有低电阈值的电极。为了最终实现降低刺激阈值的目标,我们研究了使用可生物降解的、释放神经营养因子的水凝胶(即聚乙二醇 - 聚乳酸,PEGPLA)作为一种将神经突吸引到刺激电极表面的方法。合成了释放速率在1.5至3周范围内的PEGPLA水凝胶。这些水凝胶被应用于带有溅射氧化铱电荷注入位点的多电极阵列。这些涂层对氧化铱的电化学性质影响很小,包括电荷存储容量、阻抗以及电流脉冲期间的电压瞬变。此外,我们使用PC12细胞培养模型定量研究了释放神经营养因子的PEGPLA水凝胶在体外促进神经突延伸的能力。水凝胶释放神经营养因子(神经生长因子,NGF)至少1周,神经突延伸接近NGF阳性对照,且远高于假手术组、释放牛血清白蛋白的丸剂组和阴性对照组所观察到的延伸。这些结果表明,释放神经营养因子的水凝胶可应用于多电极阵列,并提出了一种改善神经元与电极接近程度的方法,这可能会降低电刺激阈值。较低的阈值有助于制造更小的电极结构和高密度电极假体,极大地增强假体的控制和功能。