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Biosafety assessment of conducting nanostructured materials by using co-cultures of neurons and astrocytes
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-07-18 , DOI: 10.1016/j.neuro.2018.07.010
Mathieu P. Lichtenstein , Nina M. Carretero , Estela Pérez , Marta Pulido-Salgado , Javier Moral-Vico , Carme Solà , Nieves Casañ-Pastor , Cristina Suñol

Neural electrode implants are made mostly of noble materials. We have synthesized a nanostructured material combining the good electrochemical properties of iridium oxide (IrOx) and carbon-nanotubes (CNT) and the properties of poly(3,4-ethylenedioxythiophene) (PEDOT). IrOx-CNT-PEDOT charge storage capacity was lower than that of IrOx and IrOx-CNT, but higher than that of other PEDOT-containing hybrids and Pt. Cyclic voltammetry, SEM, XPS and micro-Raman spectroscopy suggest that PEDOT encapsulates IrOx and CNT. In our search for a cell culture platform that could optimize modelling the in vivo environment, we determined cell viability, neuron and astrocyte functionality and the response of astrocytes to an inflammatory insult by using primary cultures of neurons, of astrocytes and co-cultures of both. The materials tested (based on IrOx, CNT and PEDOT, as well as Pt as a reference) allowed adhesion and proliferation of astrocytes and full compatibility for neurons grown in co-cultures. Functionality assays show that uptake of glutamate in neuron-astrocyte co-culture was significantly higher than the sum of the uptake in astrocytes and neurons. In co-cultures on IrOx, IrOx-CNT and IrOx-CNT-PEDOT, glutamate was released by a depolarizing stimulus and induced a significant increase in intracellular calcium, supporting the expression of functional NMDA/glutamate receptors. LPS-induced inflammatory response in astrocytes showed a decreased response in NOS2 and COX2 mRNA expression for IrOx-CNT-PEDOT. Results indicate that neuron-astrocyte co-cultures are a reliable model for assessing the biocompatibility and safety of nanostructured materials, evidencing also that hybrid IrOx-CNT-PEDOT nanocomposite materials may offer larger resistance to inflammatory insults.



中文翻译:

通过使用神经元和星形胶质细胞的共培养来进行纳米结构材料的生物安全性评估

神经电极植入物主要由贵金属制成。我们已经合成了一种纳米结构的材料,该材料结合了氧化铱(IrOx)和碳纳米管(CNT)的良好电化学性能以及聚(3,4-乙撑二氧噻吩)(PEDOT)的性能。IrOx-CNT-PEDOT的电荷存储容量低于IrOx和IrOx-CNT的电荷存储容量,但高于其他含PEDOT的杂化物和Pt的电荷存储容量。循环伏安法,SEM,XPS和显微拉曼光谱表明,PEDOT封装了IrOx和CNT。在我们寻找可以优化体内建模的细胞培养平台的过程在环境中,我们通过使用神经元,星形胶质细胞和二者的共培养物,确定了细胞活力,神经元和星形胶质细胞功能以及星形胶质细胞对炎性损伤的反应。测试的材料(基于IrOx,CNT和PEDOT,以及以Pt为参考)允许星形胶质细胞粘附和增殖,并与共培养的神经元完全相容。功能测定表明,神经元-星形细胞共培养物中谷氨酸的摄取显着高于星形胶质细胞和神经元中摄取的总和。在IrOx,IrOx-CNT和IrOx-CNT-PEDOT的共培养物中,谷氨酸通过去极化刺激释放,并诱导细胞内钙的显着增加,从而支持功能性NMDA /谷氨酸受体的表达。LPS诱导的星形胶质细胞炎症反应显示IrOx-CNT-PEDOT的NOS2和COX2 mRNA表达下降。结果表明,神经元-星形细胞共培养是评估纳米结构材料的生物相容性和安全性的可靠模型,也证明了IrOx-CNT-PEDOT纳米复合材料可以提供更大的抵抗炎症的能力。

更新日期:2018-07-18
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