Du Zhanhong Jeff, Kolarcik Christi L, Kozai Takashi D Y, Luebben Silvia D, Sapp Shawn A, Zheng Xin Sally, Nabity James A, Cui X Tracy
Department of Bioengineering, University of Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA; Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Department of Bioengineering, University of Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA; Systems Neuroscience Institute, University of Pittsburgh, PA, USA.
Acta Biomater. 2017 Apr 15;53:46-58. doi: 10.1016/j.actbio.2017.02.010. Epub 2017 Feb 6.
Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants.
One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young's modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use.
长期植入的神经多电极阵列(MEA)是用于记录神经元电信号和/或通过刺激调节神经活动的一项关键技术。然而,目前的MEA,无论何种类型,都会引发炎症反应,最终导致设备失效。传统上,像钨和硅这样的刚性材料已被用于与相对柔软的神经组织进行连接。较大的刚度不匹配被认为会加剧炎症反应。为了尽量减少设备与大脑之间的差异,我们制造了新型超软电极,其由弹性体和导电聚合物组成,与以前的神经植入物相比,其机械性能与脑组织的机械性能更为相似。在本研究中,使用带有聚乙二醇(PEG)胶水的不锈钢穿梭器插入并释放这些超软微电极。植入的微丝在急性神经刺激中显示出功能。当植入1周或8周时,与尺寸和表面化学性质相似的钨丝相比,新型软植入物在第8周时炎症组织反应明显减少。此外,与聚合物植入物相比,在钨植入物附近发现更高程度的细胞体变形。我们的结果支持将这些新型超软电极用于长期神经植入。
将神经记录/刺激电极技术转化为用于脑机接口(BCI)或深部脑刺激(DBS)应用的临床可行设备面临的一个关键挑战是由于炎症组织反应导致设备性能的慢性退化。虽然许多人推测柔软灵活的设备会引发较少的炎症组织反应,但软植入物和硬植入物之间尚未进行严格比较。我们开发了一种杨氏模量低于1MPa的超软微电极,非常接近脑组织模量。在此,我们对这种新型超软电极和具有相同尺寸、形状和表面化学性质的传统硬电极进行了严格的组织学比较,它们在大鼠脑中植入了1周和8周。超软电极在炎症组织反应、电极 - 组织整合以及对附近神经元的机械干扰等方面都有显著改善。本研究开发了一系列新技术,从插入穿梭器到微电极的原位切片再到自动细胞形状分析,所有这些都应为该领域贡献新方法。最后,我们展示了超软电极的电功能,证明了柔性神经植入设备在未来研究和临床应用中的潜力。