Department of Chemical Engineering, ‡Department of Biomedical Engineering, §Department of Radiology, ⊥Department of Materials Science, and ∥Biointerface Institute, University of Michigan , Ann Arbor, Michigan 48109, United States.
ACS Nano. 2013 Sep 24;7(9):7619-29. doi: 10.1021/nn402074y. Epub 2013 Aug 27.
Current neural prosthetic devices (NPDs) induce chronic inflammation due to complex mechanical and biological reactions related, in part, to staggering discrepancies of mechanical properties with neural tissue. Relatively large size of the implants and traumas to blood-brain barrier contribute to inflammation reactions, as well. Mitigation of these problems and the realization of long-term brain interface require a new generation of NPDs fabricated from flexible materials compliant with the brain tissue. However, such materials will need to display hard-to-combine mechanical and electrical properties which are not available in the toolbox of classical neurotechnology. Moreover, these new materials will concomitantly demand different methods of (a) device micromanufacturing and (b) surgical implantation in brains because currently used processes take advantage of high stiffness of the devices. Carbon nanotubes (CNTs) serve as a promising foundation for such materials because of their record mechanical and electrical properties, but CNT-based tissue-compliant devices have not been realized yet. In this study, we formalize the mechanical requirements to tissue-compliant implants based on critical rupture strength of brain tissue and demonstrate that miniature CNT-based devices can satisfy these requirements. We fabricated them using MEMS-like technology and miniaturized them so that at least two dimensions of the electrodes would be comparable to brain tissue cells. The nanocomposite-based flexible neural electrodes were implanted into the rat motor cortex using a surgical procedure specifically designed for soft tissue-compliant implants. The post-surgery implant localization in the motor cortex was successfully visualized with magnetic resonance and photoacoustic imaging. In vivo functionality was demonstrated by successful registration of the low-frequency neural recording in the live brain of anesthetized rats. Investigation of inflammation processes around these electrodes will be required to establish their prospects as long-term neural electrodes.
当前的神经假体设备(NPD)由于与神经组织的机械性能差异很大相关的复杂机械和生物反应而引起慢性炎症。植入物的相对较大尺寸和对血脑屏障的创伤也会导致炎症反应。这些问题的缓解和长期脑接口的实现需要新一代由与脑组织兼容的柔性材料制成的 NPD。然而,这些材料将需要显示难以结合的机械和电气特性,而这些特性在经典神经技术的工具包中不可用。此外,由于目前使用的工艺利用了设备的高刚度,这些新材料将同时需要不同的(a)设备微制造和(b)大脑植入方法。碳纳米管(CNT)因其出色的机械和电气性能而成为此类材料的有前途的基础,但基于 CNT 的组织顺应性设备尚未实现。在这项研究中,我们根据脑组织的临界破裂强度来确定组织顺应性植入物的机械要求,并证明微型基于 CNT 的设备可以满足这些要求。我们使用类似于 MEMS 的技术制造了它们,并将其小型化,以使电极的至少两个维度与脑组织细胞相当。使用专门为软组织顺应性植入物设计的手术程序将基于纳米复合材料的柔性神经电极植入大鼠运动皮层。使用磁共振和光声成像成功地可视化了手术后在运动皮层中的植入物定位。通过成功记录麻醉大鼠活体大脑中的低频神经记录来证明体内功能。需要研究这些电极周围的炎症过程,以确定它们作为长期神经电极的前景。