Laboratory for Neuroengineering, Department of Health Sciences and Technology, Institute for Robotics and Intelligent Systems, ETH Zürich, 8092 Zürich, Switzerland.
Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center, BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, D-79110 Freiburg, Germany.
Biomaterials. 2022 Dec;291:121874. doi: 10.1016/j.biomaterials.2022.121874. Epub 2022 Oct 28.
Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the over-time stability of implants and the related nerve reactions are unclear. To unveil the mechanisms and inform the design of better nerve-electrode interfaces, we engaged a multifaceted approach, merging functional responses from patients, their histological data, and corresponding computational modelling. Neurostimulation evoked different selective sensation locations and qualities over-time, with respective perceptual thresholds, that showed different degree of time stabilities dependent from the stimulating active sites. The histological analysis after explant showed mild tissue reactions, while electromechanically active sites and substrates remained conserved. Computational models, based on patients' histology, revealed the direct influence of the simulated tissue reaction to change of thresholds and type of perceived sensations. Novel insights of electrode biocompatibility was observed compared to animals and the increase of thresholds could be predicted computationally. This multifaced framework suggest that future intraneural implants should have easier implantation and higher biocompatibility counteracting the sensations changes through AI-based stimulations and electrode coatings.
生物电子医学是利用植入式神经接口治疗残疾的一个有前途的领域。最近，对残余神经的外周神经刺激使截肢者获得了多种功能益处。尽管对患者生活产生了初步的积极影响，但植入物的长期稳定性以及相关的神经反应尚不清楚。为了揭示机制并为更好的神经-电极接口设计提供信息，我们采用了多方面的方法，将患者的功能反应、组织学数据和相应的计算模型结合在一起。神经刺激随时间引起不同的选择性感觉位置和质量，具有不同的感知阈值，其时间稳定性程度取决于刺激的活性部位。植入物取出后的组织学分析显示出轻微的组织反应，而机电活性部位和基底保持不变。基于患者组织学的计算模型揭示了模拟组织反应对阈值和感知感觉类型变化的直接影响。与动物相比，观察到了电极生物相容性的新见解，并且可以通过计算预测阈值的增加。这种多方面的框架表明，未来的神经内植入物应该具有更容易的植入和更高的生物相容性，通过基于人工智能的刺激和电极涂层来对抗感觉变化。
