Kim Youjoung, Mueller Natalie N, Schwartzman William E, Sarno Danielle, Wynder Reagan, Hoeferlin George F, Gisser Kaela, Capadona Jeffrey R, Hess-Dunning Allison
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA.
Micromachines (Basel). 2023 May 9;14(5):1015. doi: 10.3390/mi14051015.
Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.
皮层内神经探针既是大脑功能基础神经科学研究中的有力工具,也是旨在恢复瘫痪患者功能的脑机接口(BCI)的关键组成部分。皮层内神经探针可用于以单单元分辨率检测神经活动,也可用于高分辨率刺激小群神经元。不幸的是,皮层内神经探针在慢性时间点往往会失效,这在很大程度上是由于植入后以及在皮层中长期停留所引发的神经炎症反应。目前正在开发许多有前景的方法来规避炎症反应,包括开发炎症性较小的材料/设备设计以及提供抗氧化或抗炎疗法。在此,我们报告了我们最近的努力,即通过在探针内整合微流体通道,将旨在最小化组织应变的动态软化聚合物基质的神经保护作用与皮层内神经探针/组织界面处的局部药物递送相结合。制造工艺和设备设计均针对所得设备的机械性能、稳定性和微流体功能进行了优化。在为期六周的体内大鼠研究中,优化后的设备成功地能够递送抗氧化剂溶液。组织学数据表明,多出口设计在减少炎症标志物方面最为有效。通过药物递送和软材料相结合的方法作为一种平台技术来减轻炎症的能力,使得未来的研究能够探索其他疗法,以进一步提高皮层内神经探针在临床应用中的性能和使用寿命。