Implant-derived CoCrMo alloy nanoparticle disrupts DNA replication dynamics in neuronal cells.

The complexity of cobalt-chromium-molybdenum (CoCrMo) nanoparticles generated from the hip modular taper interfaces resulted in inconclusive outcomes on the level of toxicity in orthopedic patients. We used a hip simulator to generate physiologically relevant CoCrMo degradation products (DPs) to demonstrate the variation in the level of toxicity in neurons in comparison to processed degradation products (PDPs). The study outcomes indicate that DP induces a higher level of DNA damage in the form of double- and single-stranded DNA breaks and alkaline labile DNA adducts versus PDPs. The scientific advancements of this study are the following: (i) how DPs mimic more closely to the implant debris from hip implants in terms of bioactivity, (ii) how hip implant debris causes local and systemic issues, and (iii) methods to augment the biologic impact of implant debris. We discovered that DP is bioactive compared with PDP, and this should be considered in the toxicity evaluation related to implants. • The physicochemical characteristics of the CoCrMo is a major factor to consider for implant-related cytotoxicity or genotoxicity experimental design. • Elevated levels of intracellular ROS induced by the physiologically relevant wear particle are detrimental to the neuronal cells. • The DP can induce variation in DNA replication dynamics compared to PDP.

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