Physico-chemical characteristics of the CoCrMo degradation products have played an important role in cytotoxicity and clinical complications on the orthopedic patients who have metal implants. Previous studies have limited reflection on the physicochemical characteristics of the degradation products generated in vivo, which are very different from individual metal particles and/or ions obtained from different commercial sources. In this study, we aimed to understand the differences in toxicity induced by the degradation products in as-synthesized form as well as those obtained after post-processing. The degradation products were generated using a hip-simulator by maintaining physiological conditions closer to in vivo and separated into two batches, one with processing by washing and drying called processed degradation products (PDP) and another batch as ‘as-synthesized’ degradation product (DP). We studied the dose-dependent toxicity response by neural cells derived from induced pluripotent stem cells. The results of the study show that as-synthesized DPs are more toxic to neural cells even at lower concentrations studied with evident low TC50 (1–5 μg/ml) concentrations compared to PDP (25 μg/ml). Flow cytometric analysis showed a significant (p<.01) increase in uptake of the particles after 24 h and corresponding ROS production in DP-treated cells. RT-PCR analysis of oxidative specific gene expression showed, elevated mRNA levels of NADPH oxidase-1, nuclear transcription factor, superoxide dismutase-2 and glutaredoxin-2 in DP-treated cells after 6 h. The results of the study provided a clear evidence of the differential response of neural cells on the degradation products as a function of concentrations and their chemical nature.

中文翻译：

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髋关节模拟器对神经细胞产生的CoCrMo降解产物的加工态和非加工态的差异毒性

CoCrMo降解产物的理化特性在具有金属植入物的整形外科患者的细胞毒性和临床并发症中起着重要作用。先前的研究对体内产生的降解产物的理化特性的反映有限，这与从不同商业来源获得的单个金属颗粒和/或离子有很大不同。在这项研究中，我们旨在了解合成形式的降解产物以及后处理后获得的降解产物所引起的毒性差异。使用髋关节模拟器通过保持生理条件更接近体内来产生降解产物然后分为两批，一批通过洗涤和干燥进行处理，称为加工后的降解产物（PDP），另一批为“合成后的”降解产物（DP）。我们研究了来自诱导性多能干细胞的神经细胞的剂量依赖性毒性反应。研究结果表明，与PDP（25μg/ ml）相比，即使在较低的TC50（1-5μg/ ml）浓度下，合成后的DPs对神经细胞的毒性更高。流式细胞仪分析显示显著（p<.01）在DP处理的细胞中24小时后，颗粒的吸收增加，相应的ROS产生。氧化特异性基因表达的RT-PCR分析显示，DP处理细胞6小时后，NADPH氧化酶-1，核转录因子，超氧化物歧化酶-2和谷胱甘肽-2的mRNA水平升高。研究结果提供了清晰的证据，表明神经细胞对降解产物的不同反应是浓度及其化学性质的函数。