Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129, Padua, Italy.
Bioacoustics Research Laboratory, Department of Neurosciences, University of Padua, 35129, Padua, Italy; Foundation Onlus "Staminali e Vita", 35138, Padua, Italy.
Colloids Surf B Biointerfaces. 2019 Jan 1;173:400-406. doi: 10.1016/j.colsurfb.2018.10.005. Epub 2018 Oct 6.
Cochlear implants, the only way to recover from severe/profound hearing loss, may cause adverse effects, among which reactions to silicone materials coating implant electrodes, leading to apoptosis and necrosis of spiral ganglion cells. Our aim was to evaluate whether three polydimethylsiloxane (PDMS) compounds (hexadimethylsiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane) used in silicone rods could exert toxic effects on an in vitro neuronal cell model (PC12). Cell viability, morphology and mRNA expression levels of apoptotic markers were evaluated on PC12 cells at different PDMS dilutions up to 6 days of exposure. The results showed that at the highest concentrations tested cell viability was reduced by hexadimethylsiloxane and octamethyltrisiloxane at all times of exposure, but only from 72 h onwards by decamethylcyclopentasiloxane. The number of neurites per cell was not affected by hexadimethylsiloxane, but was significantly reduced from 24 h onwards by octamethyltrisiloxane and decamethylcyclopentasiloxane. Neurite length was reduced by hexadimethylsiloxane only at 24 h, and by octamethyltrisiloxane and decamethylcyclopentasiloxane at all exposure intervals. In controls exposed to silicone or glass rods cell viability was reduced only after 24 h, but neurite number and length was never reduced at any exposure interval. Biomolecular investigations showed that apoptotic markers did not change in any experimental condition, suggesting that PDMS are biocompatible. The reduction of cell viability and neurite number and length caused by exposure to these compounds was probably caused by a PDMS surface film formed over the cell medium, preventing air exchange, and not by the release of cytotoxic molecules.
人工耳蜗植入,这是治疗重度/极重度听力损失的唯一方法,可能会产生不良反应,其中包括对硅材料涂层的植入电极的反应,导致螺旋神经节细胞凋亡和坏死。我们的目的是评估三种聚二甲基硅氧烷(PDMS)化合物(六甲基二硅氧烷、八甲基三硅氧烷、十甲基环五硅氧烷)在硅胶棒中是否会对体外神经元细胞模型(PC12)产生毒性作用。在不同 PDMS 稀释度下,评价 PC12 细胞的细胞活力、形态和凋亡标志物的 mRNA 表达水平,直至暴露 6 天。结果表明,在最高浓度测试中,六甲基二硅氧烷和八甲基三硅氧烷在所有暴露时间内均降低细胞活力,但仅在暴露 72 小时后,十甲基环五硅氧烷才降低细胞活力。每个细胞的神经突数量不受六甲基二硅氧烷的影响,但从 24 小时开始,八甲基三硅氧烷和十甲基环五硅氧烷显著减少。神经突长度仅在 24 小时时被六甲基二硅氧烷减少,在所有暴露时间间隔内被八甲基三硅氧烷和十甲基环五硅氧烷减少。在暴露于硅胶或玻璃棒的对照物中,细胞活力仅在 24 小时后降低,但在任何暴露时间间隔内,神经突数量和长度都没有降低。生物分子研究表明,在任何实验条件下,凋亡标志物都没有改变,这表明 PDMS 是生物相容的。这些化合物暴露引起的细胞活力和神经突数量和长度的减少可能是由于在细胞培养基上形成的 PDMS 表面膜,阻止了空气交换,而不是由于释放细胞毒性分子引起的。