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

Bijukumar, Divya; Segu, Abhijith; Mou, Yongchao; Ghodsi, Reza; Shokufhar, Tolou; Barba, Mark; Li, Xuejun; Mathew, Mathew T.

doi:10.1080/17435390.2018.1498929

Cited by 11 publications

(13 citation statements)

References 72 publications

(75 reference statements)

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“…Wear particles at concentrations in the range of 10–0.1 µg/ml were added to cell cultures for 24 h of incubation. In a previous study by Bijukumar et al we observed that concentrations above 10 µg/ml caused a reduction in cell growth to less than 40% in the case of neuronal cells. Hence, in this experiment, we selected concentrations from 10 to 0.1 μg/ml to evaluate their effect on the cells of interest in this study.…”

Section: Methodsmentioning

confidence: 65%

“…(C) Results of the energy‐dispersive X‐ray spectroscopy (EDS) analysis of CoCrMo wear debris to confirm the presence of cobalt and chromium. The results are qualitatively due to the fact that lighter elements such as carbon and oxygen cannot be accurately quantified by this EDS system . However, there appeared to be a fairly large amount of oxygen indicating the presence of metal oxides, likely chromium oxide.…”

Section: Resultsmentioning

confidence: 92%

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In Vitro Evidence for Cell‐Accelerated Corrosion Within Modular Junctions of Total Hip Replacements

Bijukumar

Salunkhe

Morris

et al. 2019

Journal Orthopaedic Research

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Corrosion at modular junctions of total hip replacement (THR) remains a major concern today. Multiple types of damage modes have been identified at modular junctions, correlated with different corrosion characteristics that may eventually lead to implant failure. Recently, within the head-taper region of the CoCrMo retrieval implants, cell-like features and trails of etching patterns were observed that could potentially be linked to the involvement of cells of the periprosthetic region. However, there is no experimental evidence to corroborate this phenomenon. Therefore, we aimed to study the potential role of periprosthetic cell types on corrosion of CoCrMo alloy under different culture conditions, including the presence of CoCrMo wear debris. Cells were incubated with and without CoCrMo wear debris (obtained from a hip simulator) with an average particle size of 119 ± 138 nm. Electrochemical impedance spectroscopy (EIS) was used to evaluate the corrosion tendency, corrosion rate, and corrosion kinetics using the media after 24 h of cell culture as the electrolyte. Results of the study showed that there was lower corrosion resistance (p < 0.02) and higher capacitance (p < 0.05) within cell media from macrophages challenged with particles when compared with the other media conditions studied. The potentiodynamic results were also in agreement with the EIS values, showing significantly higher corrosion tendency (low E corr ) (p < 0.0001) and high I corr (p < 0.05) in media from challenged macrophages compared with media with H 2 O 2 solution. Overall, the study provides in vitro experimental evidence for the possible role of macrophages in altering the chemical environment within the crevice and thereby accelerating corrosion of CoCrMo alloy.

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Section: Methodsmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 92%

In Vitro Evidence for Cell‐Accelerated Corrosion Within Modular Junctions of Total Hip Replacements

Bijukumar

Salunkhe

Morris

et al. 2019

Journal Orthopaedic Research

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“…The majority of particles appear to be chromium oxide, but alloy particles, chromium phosphate, and metallo-organic complexes have also been reported. 46 Our group has previously established the differential response by the processed and unprocessed states of degradation products obtained from hip simulator in inducing neurodegeneration 47 . Hence, it is imperative to study the differentiation of macrophages in response to the clinically relevant wear particles to improve our understanding of macrophage action at the taper interface.…”

Section: Macrophage Polarization By Nanomaterialsmentioning

confidence: 99%

“…The original stock solution was stored at −20°C and an aliquot of stock was refrigerated at 4°C (0-4 months) until use. The endotoxin levels of the particle samples were checked prior to cell culture tests 47 .…”

Section: Wear Particles Generationmentioning

confidence: 99%

“…THP-1 monocytes were treated with 5 ng/mL PMA (Sigma, P1585) for 24 h. Further, the cells were treated in three different conditions 1) M1 macrophages by incubating with, 20 ng/mL IFN-γ (R&D systems, Cat# 285-IF-100), and 10 pg/mL LPS (Sigma, #8630), 2) M2 polarization by incubating cells with 20 ng/mL IL-4 (R&D Systems, Cat#204-IL-010)), and 20 ng/mL IL-13 (R&D Systems, Cat#213-ILB-005) 49 and, 3) M CA cells were generated by treating CoCr wear particles at a concentration of 1 μg/mL to M0 macrophages for a period of 24 hours (Figure 2a). The concentration of wear particles was chosen based on the dose-dependent toxicity evaluation reported in our previous studies on neuronal cells 47 , monocytes, macrophages and osteoblast cells 9 . The results from the previous study showed that the concentration of wear particles required to challenge the monocytes and macrophages with >88% viability after 24 hours was 1 μg/ml.…”

Section: Cell Culturementioning

confidence: 99%

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Wear particles induce a new macrophage phenotype with the potential to accelerate material corrosion within total hip replacement interfaces

et al. 2020

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Evidence that macrophages can play a role in accelerating corrosion in CoCrMo alloy in total hip replacement (THR) interfaces leads to questions regarding the underlying cellular mechanisms and immunological responses. Hence, we evaluated the role of macrophages in corrosion processes using the cell culture supernatant from different conditions and the effect of wear particles on macrophage dynamics. Monocytes were exposed to CoCrMo wear particles and their effect on macrophage differentiation was investigated by comparisons with M1 and M2 macrophage differentiation. Corrosion associated macrophages (M CA macrophages) exhibited upregulation of TNF-α, iNOS, STAT-6, and PPARG and down-regulation of CD86 and ARG, when compared to M1 and M2 macrophages. M CA cells also secreted higher levels of IL-8, IL-1β, IL-6, IL-10, TNFα, and IL-12p70 than M1 macrophages and/or M2 macrophages. Our findings revealed variation in macrophage phenotype (M CA ) induced by CoCrMo wear particles in generating a chemical environment that induces cell-accelerated corrosion of CoCrMo alloy at THR modular interfaces.

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Dynamic microfluidic bioreactor—Hip simulator (DMBH) system for implant toxicity monitoring

Badhe

Bijukumar

Mesquita

et al. 2021

Biotech & Bioengineering

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The generation of degradation products (DPs) like ions and organo-metallic particles from corroding metallic implants is an important healthcare concern. These DPs generate local and systemic toxicity. The impact on local toxicity is well documented, however, little is known about systemic toxicity. This is mainly due to the limited scope of the current microtiter plate-based (static) toxicity assay techniques. These methods do not mimic the systemic (dynamic) conditions. In this study, it is hypothesized that DPs incubated with cells in static conditions might provide improper systemic toxicity results, as there is no movement mimicking the blood circulation around cells. This study reports the development of a three-chambered prototype microfluidic system connected to the operational hip implant simulator to test the cellular response induced by the DPs. This setup is called a dynamic microfluidic bioreactor-hip simulator system. We hypothesize that a dynamic microfluidic system will provide a realistic toxicology response induced by DPs than a static cell culture plate. To prove the hypothesis, Neuro2a (N2a) cells were used as representative cells to study systemic neurotoxicity by the implant DPs. The microfluidic bioreactor system was validated by comparing the cell toxicity against the traditional static system and using COMSOL modeling for media flow with DPs. The hip implant simulator used in this study was a state-of-the-art sliding hip simulator developed in our lab. The results suggested that static toxicity was significantly more compared to dynamic microfluidic-based toxicity. The newly developed DMBH system tested for in situ systemic toxicity on N2a cells and demonstrated very minimum toxicity level (5.23%) compared to static systems (31.16%). Thus, the new DMBH system is an efficient tool for in situ implant metal systemic toxicity testing.

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

Cited by 11 publications

References 72 publications

In Vitro Evidence for Cell‐Accelerated Corrosion Within Modular Junctions of Total Hip Replacements

In Vitro Evidence for Cell‐Accelerated Corrosion Within Modular Junctions of Total Hip Replacements

Wear particles induce a new macrophage phenotype with the potential to accelerate material corrosion within total hip replacement interfaces

Dynamic microfluidic bioreactor—Hip simulator (DMBH) system for implant toxicity monitoring

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