Abstract：
Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer interfacing technologies. However, it is well known since the 1970s that Pt dissolution occurs with electrical stimulation. More recent clinical and in vivo studies have shown signs of corrosion in explanted electrode arrays and the presence of Pt-containing particulates in tissue samples. The process of degradation and release of metallic ions and particles can significantly impact on device performance. Moreover, the effects of Pt dissolution products on tissue health and function are still largely unknown. This is due to the highly complex chemistry underlying the dissolution process and the difficulty in decoupling electrical and chemical effects on biological responses. Understanding the mechanisms and effects of Pt dissolution proves challenging as the dissolution process can be influenced by electrical, chemical, physical, and biological factors, all of them highly variable between experimental settings. By evaluating comprehensive findings on Pt dissolution mechanisms reported in the fuel cell field, this review presents a critical analysis of the possible mechanisms that drive Pt dissolution in neural stimulation in vitro and in vivo. Stimulation parameters, such as aggregate charge, charge density, and electrochemical potential can all impact the levels of dissolved Pt. However, chemical factors such as electrolyte types, dissolved gases, and pH can all influence dissolution, confounding the findings of in vitro studies with multiple variables. Biological factors, such as proteins, have been documented to exhibit a mitigating effect on the dissolution process. Other biological factors like cells and fibro-proliferative responses, such as fibrosis and gliosis, impact on electrode properties and are suspected to impact on Pt dissolution. However, the relationship between electrical properties of stimulating electrodes and Pt dissolution remains contentious. Host responses to Pt degradation products are also controversial due to the unknown chemistry of Pt compounds formed and the lack of understanding of Pt distribution in clinical scenarios. The cytotoxicity of Pt produced via electrical stimulation appears similar to Pt-based compounds, including hexachloroplatinates and chemotherapeutic agents like cisplatin. While the levels of Pt produced under clinical and acute stimulation regimes were typically an order of magnitude lower than toxic concentrations observed in vitro, further research is needed to accurately assess the mass balance and type of Pt produced during long-term stimulation and its impact on tissue response. Finally, approaches to mitigating the dissolution process are reviewed. A wide variety of approaches, including stimulation strategies, coating electrode materials, and surface modification techniques to avoid excess charge during stimulation and minimise tissue response, may ultimately support long-term and safe operation of neural stimulating devices.
摘要：
铂（Pt）是耳蜗植入物等植入式神经假体中电极的首选金属，深层大脑刺激装置，和脑机接口技术。然而,众所周知，自20世纪70年代以来，Pt溶解伴随着电刺激而发生。最近的临床和体内研究已经显示外植电极阵列中的腐蚀迹象和组织样品中的含Pt颗粒的存在。金属离子和颗粒的降解和释放过程会显著影响器件性能。此外，铂溶解产物对组织健康和功能的影响仍在很大程度上未知。这是由于溶解过程背后的高度复杂的化学以及对生物响应的电和化学效应解耦的困难。了解铂溶解的机制和效果证明具有挑战性，因为溶解过程可能会受到电，化学,物理，和生物因素，所有这些都在实验设置之间高度可变。通过评估燃料电池领域报道的Pt溶解机制的综合发现，这篇综述对体外和体内神经刺激中驱动Pt溶解的可能机制进行了严格的分析。刺激参数,例如聚集电荷，电荷密度,和电化学电势都可以影响溶解的Pt的水平。然而,化学因素，如电解质类型，溶解气体，和pH都会影响溶解，将体外研究的结果与多个变量混淆。生物因素,如蛋白质，已被证明对溶解过程具有缓解作用。其他生物因素，如细胞和纤维增殖反应，如纤维化和胶质增生，对电极性能的影响，并怀疑对Pt溶解的影响。然而,刺激电极的电特性与Pt溶解之间的关系仍然存在争议。宿主对Pt降解产物的反应也是有争议的,这是由于所形成的Pt化合物的化学未知以及缺乏对临床情景中Pt分布的了解。通过电刺激产生的Pt的细胞毒性与基于Pt的化合物相似，包括六氯铂和化疗药物如顺铂。虽然在临床和急性刺激方案下产生的Pt水平通常比体外观察到的毒性浓度低一个数量级，需要进一步的研究来准确评估长期刺激过程中产生的Pt的质量平衡和类型及其对组织反应的影响。最后,综述了减轻溶解过程的方法。各种各样的方法，包括刺激策略，涂层电极材料，和表面改性技术，以避免刺激过程中的过量电荷和最小化组织反应，可能最终支持神经刺激装置的长期和安全运行。
