Aman Martin, Bergmeister Konstantin D, Festin Christopher, Sporer Matthias E, Russold Michael Friedrich, Gstoettner Clemens, Podesser Bruno K, Gail Alexander, Farina Dario, Cederna Paul, Aszmann Oskar C
Clinical Laboratory for Bionic Extremity Reconstruction, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Division of Biomedical Research, Medical University of Vienna, Vienna, Austria.
Front Neurosci. 2020 Jan 30;13:1442. doi: 10.3389/fnins.2019.01442. eCollection 2019.
Man-machine interfacing remains the main challenge for accurate and reliable control of bionic prostheses. Implantable electrodes in nerves and muscles may overcome some of the limitations by significantly increasing the interface's reliability and bandwidth. Before human application, experimental preclinical testing is essential to assess chronic biocompatibility and functionality. Here, we analyze available animal models, their costs and ethical challenges in special regards to simulating a potentially life-long application in a short period of time and in non-biped animals. We performed a literature analysis following the PRISMA guidelines including all animal models used to record neural or muscular activity via implantable electrodes, evaluating animal models, group size, duration, origin of publication as well as type of interface. Furthermore, behavioral, ethical, and economic considerations of these models were analyzed. Additionally, we discuss experience and surgical approaches with rat, sheep, and primate models and an approach for international standardized testing. Overall, 343 studies matched the search terms, dominantly originating from the US (55%) and Europe (34%), using mainly small animal models (rat: 40%). Electrode placement was dominantly neural (77%) compared to muscular (23%). Large animal models had a mean duration of 135 ± 87.2 days, with a mean of 5.3 ± 3.4 animals per trial. Small animal models had a mean duration of 85 ± 11.2 days, with a mean of 12.4 ± 1.7 animals. Only 37% animal models were by definition chronic tests (>3 months) and thus potentially provide information on long-term performance. Costs for large animals were up to 45 times higher than small animals. However, costs are relatively small compared to complication costs in human long-term applications. Overall, we believe a combination of small animals for preliminary primary electrode testing and large animals to investigate long-term biocompatibility, impedance, and tissue regeneration parameters provides sufficient data to ensure long-term human applications.
人机交互仍然是精确可靠地控制仿生假肢的主要挑战。神经和肌肉中的可植入电极可能会通过显著提高接口的可靠性和带宽来克服一些限制。在应用于人体之前，实验性临床前测试对于评估长期生物相容性和功能至关重要。在此，我们分析了可用的动物模型、它们的成本以及伦理挑战，特别关注在短时间内和非两足动物中模拟潜在的终身应用。我们按照PRISMA指南进行了文献分析，涵盖所有用于通过可植入电极记录神经或肌肉活动的动物模型，评估动物模型、组规模、持续时间、出版物来源以及接口类型。此外，还分析了这些模型的行为、伦理和经济因素。此外，我们讨论了大鼠、绵羊和灵长类动物模型的经验和手术方法以及国际标准化测试方法。总体而言，343项研究符合搜索条件，主要来自美国（55%）和欧洲（34%），主要使用小型动物模型（大鼠：40%）。与肌肉电极（23%）相比，电极放置主要为神经电极（77%）。大型动物模型的平均持续时间为135±87.2天，每次试验平均有5.3±3.4只动物。小型动物模型的平均持续时间为85±11.2天，平均有12.4±1.7只动物。根据定义，只有37%的动物模型是长期测试（>3个月），因此可能提供有关长期性能的信息。大型动物的成本比小型动物高出45倍。然而，与人类长期应用中的并发症成本相比，这些成本相对较小。总体而言，我们认为结合使用小型动物进行初步的初级电极测试和大型动物来研究长期生物相容性、阻抗和组织再生参数，可以提供足够的数据来确保长期的人体应用。
