Use of cortical neuronal networks for in vitro material biocompatibility testing
Use of cortical neuronal networks for in vitro material biocompatibility testing
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DOI：
10.1016/j.bios.2013.10.002
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发表时间：
2014-03-15
影响因子：
12.6
通讯作者：
Pancrazio, Joseph J.
中科院分区：
文献类型：
--
作者：
Charkhkar, Hamid;Frewin, Christopher;Pancrazio, Joseph J.
神经接口旨在恢复在疾病或损伤期间失去的神经功能。新型可植入神经接口越来越多地利用新型材料来实现与神经系统的微尺度耦合。与任何生物医学器械一样，神经接口应包含符合国际标准ISO 10993 -5的生物相容性材料，该标准描述了涉及成纤维细胞的体外试验，其中细胞毒性作为主要终点。在本研究中，我们研究了活的神经元网络作为体外材料生物相容性的功能测定的效用，特别是对于包括可植入神经接口的材料。培养胚胎小鼠皮质组织以形成功能网络，其中可以使用集成基底的微电极阵列无创地监测自发动作电位或尖峰。利用这样的平台，我们以与ISO 10993-5指南一致的方法将已建立的阳性和阴性对照材料暴露于神经元网络。暴露于阴性对照（金和聚乙烯）未显著改变神经元活性，而阳性对照（铜和聚氯乙烯（PVC））导致网络尖峰速率降低。我们还比较了功能测定与使用L929成纤维细胞的既定细胞毒性测量。我们的研究结果表明，神经元网络表现出增强的敏感性阳性对照材料。此外，我们还评估了钨（一种常见的微电极材料）和两种导电聚合物制剂的功能性神经毒性，这两种导电聚合物制剂已用于修改微电极的体内记录和刺激特性。这些数据表明，培养的神经元网络是一个有用的平台，用于评估预期植入神经系统的材料的功能毒性。(C)2013爱思唯尔有限公司版权所有。
Neural interfaces aim to restore neurological function lost during disease or injury. Novel implantable neural interfaces increasingly capitalize on novel materials to achieve microscale coupling with the nervous system. Like any biomedical device, neural interfaces should consist of materials that exhibit biocompatibility in accordance with the international standard ISO10993-5, which describes in vitro testing involving fibroblasts where cytotoxicity serves as the main endpoint. In the present study, we examine the utility of living neuronal networks as functional assays for in vitro material biocompatibility, particularly for materials that comprise implantable neural interfaces. Embryonic mouse cortical tissue was cultured to form functional networks where spontaneous action potentials, or spikes, can be monitored non-invasively using a substrate-integrated microelectrode array. Taking advantage of such a platform, we exposed established positive and negative control materials to the neuronal networks in a consistent method with ISO 10993-5 guidance. Exposure to the negative controls, gold and polyethylene, did not significantly change the neuronal activity whereas the positive controls, copper and polyvinyl chloride (PVC), resulted in reduction of network spike rate. We also compared the functional assay with an established cytotoxicity measure using L929 fibroblast cells. Our findings indicate that neuronal networks exhibit enhanced sensitivity to positive control materials. In addition, we assessed functional neurotoxicity of tungsten, a common microelectrode material, and two conducting polymer formulations that have been used to modify microelectrode properties for in vivo recording and stimulation. These data suggest that cultured neuronal networks are a useful platform for evaluating the functional toxicity of materials intended for implantation in the nervous system. (C) 2013 Elsevier B.V. All rights reserved.