Elyahoodayan Sahar, Larson Christopher, Cobo Angelica M, Meng Ellis, Song Dong
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; Department of Electrical and Computer Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
J Neurosci Methods. 2020 Apr 15;336:108634. doi: 10.1016/j.jneumeth.2020.108634. Epub 2020 Feb 14.
Extraneural cuffs are among the least invasive peripheral nerve interfaces as they remain outside the nerve. However, compared with more invasive interfaces, these electrodes may suffer from lower selectivity and sensitivity since the targeted nerve fibers are more distanced from the electrodes.
A lyse-and-attract cuff electrode (LACE) was enabled by microfabrication and developed to improve selectivity and sensitivity while maintaining a cuff format. Its engineering design was described in previous work. LACE is a hybrid cuff that integrates both microelectrodes and microfluidic channels. The ultimate goal is to increase fascicular selectivity and sensitivity by focal delivery via the microchannels of (1) lysing agent to remove connective tissue separating electrodes from nerve fibers, and (2) neurotrophic factors to promote axonal sprouting of the exposed nerve fibers into microfluidic channels where electrodes are embedded. Here, we focus on demonstrating in vivo function of microfluidics and microelectrodes in an acute preparation in which we evaluate the ability to focally remove connective tissue and record and stimulate with microchannel-embedded microelectrodes neural activity in rat sciatic nerves.
While extraneural interfaces prioritize nerve health and intraneural interfaces prioritize functionality, LACE represents a new extraneural approach which could potentially excel at both aims.
Surgical implantation demonstrate preservation of LACE function following careful and minimal handling. In vivo electrical evaluation demonstrates the ability of microelectrodes placed within microfluidic channels to successfully stimulate and record compound action potentials from rat sciatic nerve. Furthermore, collagen-rich epineurium was focally removed following infusion of collagenase via microchannels and confirmed via microscopy.
The feasibility of using a cuff having integrated microelectrodes and microfluidics to stimulate, record, and deliver drug to focally lyse away the epineurium layer was demonstrated in acute experiments on rat sciatic nerve.
神经外袖套是侵入性最小的外周神经接口之一,因为它们位于神经外部。然而,与侵入性更强的接口相比,这些电极的选择性和灵敏度可能较低,因为目标神经纤维与电极的距离更远。
通过微制造技术实现了一种溶解吸引袖套电极(LACE),并在保持袖套形式的同时提高了选择性和灵敏度。其工程设计在先前的工作中已有描述。LACE是一种集成了微电极和微流体通道的混合袖套。最终目标是通过微通道进行局部递送,提高束状选择性和灵敏度,具体包括:(1)递送溶解剂以去除将电极与神经纤维分隔开的结缔组织;(2)递送神经营养因子以促进暴露的神经纤维向嵌入电极的微流体通道内进行轴突发芽。在此,我们着重在急性实验中展示微流体和微电极在大鼠坐骨神经中的体内功能,评估局部去除结缔组织以及用嵌入微通道的微电极记录和刺激神经活动的能力。
神经外接口优先考虑神经健康,神经内接口优先考虑功能,而LACE代表了一种新的神经外方法,有可能在这两个目标上都表现出色。
手术植入表明,经过仔细且最小程度的操作后,LACE功能得以保留。体内电学评估表明,放置在微流体通道内的微电极能够成功刺激并记录大鼠坐骨神经的复合动作电位。此外,通过微通道注入胶原酶后,富含胶原蛋白的神经外膜被局部去除,并通过显微镜得到证实。
在大鼠坐骨神经的急性实验中,证明了使用集成微电极和微流体的袖套进行刺激、记录以及局部溶解神经外膜层并递送药物的可行性。