Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Center for Neurotrauma, Neurodegeneration, and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.
Sci Adv. 2021 Jan 22;7(4). doi: 10.1126/sciadv.aay5347. Print 2021 Jan.
For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable "living electrodes," living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex as an in vivo proof of concept for this neural interface paradigm. The creation and characterization of these functional, optically controllable living electrodes are critical steps in developing a new class of optobiological tools for neural interfacing.
对于可植入的神经接口,无机微电极的特异性和稳定性限制了其功能/临床效果。在微电子设备和大脑之间的生物中间体能通过以下方式提高特异性和寿命:(i)与深部神经网络的自然突触整合,(ii)在大脑表面的可及性,以及 (iii)光遗传学操纵,以进行靶向、基于光的读出/控制。因此,我们已经开发出可植入的“活体电极”、活体皮质神经元和轴突束,它们被保存在柔软的水凝胶圆柱体中,用于脑活动的光学生物监测/调节。在这里,我们展示了这些组织工程构建体的制造、快速轴突生长、可重复的细胞结构以及体外的同时光学刺激和记录。我们还介绍了它们在大鼠皮层中的移植、存活、整合和光学记录,作为该神经接口范例的体内概念验证。这些功能上可控制的活体电极的创建和特性是开发用于神经接口的新型光学生物工具的关键步骤。