Differential toxicity of processed and non-processed states of CoCrMo degradation products generated from a hip simulator on neural cells

摘要

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<0.01) increase in uptake of the particles after 24h 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 6h. 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.