Instituto de Ciencia de Materiales de Madrid (ICMM), CSIC, Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, Spain.
Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071, Toledo, Spain.
Biomaterials. 2021 Dec;279:121186. doi: 10.1016/j.biomaterials.2021.121186. Epub 2021 Oct 15.
Progress in the clinical application of recording and stimulation devices for neural diseases is still limited, mainly because of suboptimal material engineering and unfavorable interactions with biological entities. Nanotechnology is providing upgraded designs of materials to better mimic the native extracellular environment and attain more intimate contacts with individual neurons, besides allowing for the miniaturization of the electrodes. However, little progress has been done to date on the understanding of the biological impact that such neural interfaces have on neural network maturation and functionality. In this work, we elucidate the effect of a gold (Au) highly ordered nanostructure on the morphological and functional interactions with neural cells and tissues. Alumina-templated Au nanostructured electrodes composed of parallel nanowires of 160 nm in diameter and 1.2 μm in length (Au-NWs), with 320 nm of pitch, are designed and characterized. Equivalent non-structured Au electrodes (Au-Flat) are used for comparison. By using diverse techniques in in vitro cell cultures including live calcium imaging, we found that Au-NWs interfaced with primary neural cortical cells for up to 14 days allow neural networks growth and increase spontaneous activity and ability of neuronal synchronization, thus indicating that nanostructured features favor neuronal network. The enhancement in the number of glial cells found is hypothesized to be behind these beneficial functional effects. The in vivo effect of the implantation of these nanostructured electrodes and its potential relevance for future clinical applicability has been explored in an experimental model of rat spinal cord injury. Subacute responses to implanted Au-NWs show no overt reactive or toxic biological reactions besides those triggered by the injury itself. These results highlight the translational potential of Au-NWs electrodes for in vivo applications as neural interfaces in contact with central nervous tissues including the injured spinal cord.
神经疾病记录和刺激设备的临床应用进展仍然有限，主要是因为材料工程不理想，与生物实体的相互作用不利。纳米技术为更好地模拟天然细胞外环境并实现与单个神经元更密切的接触提供了升级的材料设计，同时还允许电极小型化。然而，迄今为止，对于理解这种神经接口对神经网络成熟和功能的生物学影响，几乎没有取得任何进展。在这项工作中，我们阐明了金（Au）高度有序纳米结构对与神经细胞和组织的形态和功能相互作用的影响。设计并表征了由直径为 160nm 且长度为 1.2μm 的平行纳米线（Au-NWs）组成的氧化铝模板化 Au 纳米结构电极，其节距为 320nm，并使用等效的非结构化 Au 电极（Au-Flat）进行比较。通过在包括活钙成像在内的体外细胞培养中使用各种技术，我们发现与原代神经皮质细胞接触长达 14 天的 Au-NWs 允许神经网络生长并增加自发活动和神经元同步能力，这表明纳米结构特征有利于神经元网络。推测这些有益的功能效应背后是神经胶质细胞数量的增加。已经探索了这些纳米结构电极的体内植入的影响及其对未来临床应用的潜在相关性，作为与包括损伤脊髓在内的中枢神经系统接触的神经接口的实验性大鼠脊髓损伤模型。植入 Au-NWs 的亚急性反应除了损伤本身引发的反应外，没有明显的反应性或毒性生物学反应。这些结果突出了 Au-NWs 电极作为与中枢神经系统接触的神经接口在体内应用的转化潜力，包括损伤的脊髓。
