Systemic and local toxicity of metal debris released from hip prostheses: A review of experimental approaches.

Despite the technological improvements in orthopedic joint replacement implants, wear and corrosion products associated with the metal components of these implants may result in adverse local tissue and perhaps systemic reactions and toxicities. The current review encompasses a literature review of the local and systemic toxicity studies concerning the effect of CoCrMo wear debris released from wear and corrosion of orthopedic implants and prostheses. Release of metallic debris is mainly in the form of micro- and nano-particles, ions of different valences, and oxides composed of Co and Cr. Though these substances alter human biology, their direct effects of these substances on specific tissue types remain poorly understood. This may partially be the consequence of the multivariate research methodologies employed, leading to inconsistent reports. This review proposes the importance of developing new and more appropriate in-vitro methodologies to study the cellular responses and toxicity mediated by joint replacement wear debris in-vivo.

Investigation of cell-accelerated corrosion (CAC) on the CoCrMo alloy with segregation banding: Hip implant applications.

Metal alloy microstructure plays a crucial role in corrosion associated with total hip replacement (THR). THR is a prominent strategy that uses metal implants such as cobalt-chromium-molybdenum (CoCrMo) alloys due to their advantageous biological and mechanical properties. Despite all benefits, these implants undergo corrosion and wear processes in-vivo in a synergistic manner called tribocorrosion. Also, the implant retrieval findings reported that fretting corrosion occurred in-vivo, evidenced by the damage patterns that appeared on the THR junction interfaces. There is no scientific data on the studies reporting the fretting corrosion patterns of CoCrMo microstructures in the presence of specific biological treatments to date. In the current study, Flat-on-flat fretting corrosion set-up was customized and used to study the tribocorrosion patterns of fretting corrosion to understand the role of alloy microstructure. Alloy microstructural differences were created with the implant stock metal's longitudinal and transverse cutting orientations. As a result, the transverse created the non-banded, homogenous microstructure, whereas the longitudinal cut resulted in the banded, non-homogenous microstructure on the surface of the alloy (in this manuscript, the terms homogenous and banded were used). The induced currents were monitored using a three-electrode system. Three different types of electrolytes were utilized to study the fretting corrosion patterns with both homogeneous and banded microstructures: 1. Control media 2. Spent media (the macrophage cell cultured media) 3. Challenged media (media collected after the macrophage was treated with CoCrMo particles). From the electrochemical results, in the potentiostat conditions, the banded group exhibited a higher induced current in both challenged and spent electrolyte environments than in control due to the synergistic activity of CoCrMo particles and macrophage demonstrating more corrosion loss. Additionally, both Bode and Nyquist plots reported a clear difference between the banded and homogeneous microstructure, especially with challenged electrolytes becoming more corrosion-resistant post-fretting than pre-fretting results. The banded microstructure showed a unique shape of the fretting loop, which may be due to tribochemical reactions. Therefore, from the electrochemical, mechanical, and surface analysis data results, the transverse/homogenous/non-banded alloy microstructure groups show a higher resistance to fretting-corrosion damage.

Hip implant modular junction: The role of CoCrMo alloy microstructure on fretting-corrosion.

Cobalt-chromium-molybdenum (CoCrMo) alloy is one of the most used metals in total hip replacement (THR) due to the alloy's superior corrosion qualities and biocompatibility. Over time these prostheses may undergo wear and corrosion processes in a synergistic process known as tribocorrosion. Implant retrieval studies have shown that damage patterns on THR modular junction surfaces indicating specifically in vivo fretting-corrosion to take place. To date, there have been no studies on the fretting-corrosion behaviors of CoCrMo alloy under the consideration of specific microstructural features. A custom-built flat-on-flat fretting-corrosion setup was utilized to test the synergistic tribocorrosion behavior of fretting-corrosion. The difference in microstructure was generated through the cutting orientations of the transverse and the longitudinal direction of the bar stock material, where the longitudinal cut exhibits a characteristic banded microstructure (banded group) and the transverse cut a homogenous microstructure (unbanded group). A three-electrode system was employed to monitor the induced currents. Two different types of electrolytes were used in the current study: 1. Bovine calf serum (BCS-30 g/L protein) (normal conditions) 2. BCS with Lipopolysaccharide (LPS, 0.15 µg/ml) (simulated infectious conditions). In the free potential mode, banded samples showed an increased potential compared to the unbanded samples. In potentiostatic conditions, the banded group also exhibited a higher induced current in both electrolyte environments, indicating more corrosion loss. Both Nyquist and Bode plots showed both orientations of metal becoming more corrosion resistant post-fretting when compared to pre-fretting data. The longitudinal group at OCP demonstrated a unique shape of the fretting-loop, which might be related to tribochemical reactions. Based on the mechanical, electrochemical, and surface characterization data, the transverse group (unbanded) microstructures demonstrates a higher resistance to fretting-corrosion damage.

Systemic toxicity eliciting metal ion levels from metallic implants and orthopedic devices - A mini review.

The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported concurrently. Complications developed due to metal ions, metal debris, and organo-metallic particles in orthopedic patients have been a growing concern in recent years. It was reported that local and systemic toxicity caused by such released products from the implants is one of the major reasons for implant rejection and revision. Even though the description of environmental metal toxicants and safety limits for their exposure to humans were well established in the literature, an effort was not adequately performed in the case of implant-based metal toxicology. Since the metal ion concentration in serum acts as a possible indicator of the systemic toxicity, this review summarizes the reported human serum safe limits, toxic limits, and concentration range (µg/L, ppb, etc.) for mild to severe symptoms of six (cardiac, hepatic, neuro, nephron, dermal and endocrine) systemic toxicities for twelve most commonly used metallic implants. It also covers the widely used metal ion quantification techniques and systemic toxicity treatments reported.

The role of fretting-frequency on the damage modes of THR modular junction: In-vitro study.

According to the National Center for Health Statistics, currently, more than 250,000 total hip replacements annually in the US alone, with an estimated increase to 500,000 by the year 2030. The usage of tapered junctions between the femoral neck and head gives the surgeon flexibility in implant assembly. However, these modular junctions are subjected to micro-motion that may cause chemical and fretting-corrosion at the modular junction. Therefore, it is imperative to study these forces to mitigate their effects. The current study aims to understand the effects of fretting-corrosion as a function of fretting frequencies caused by common physical activities in an in-vitro model of hip modular junctions. The fretting system has a tribological contact condition of flat-on-flat, mounted to a load frame. CoCrMo pins were polished and immersed in a synovial fluid-like electrolyte solution (Bovine calf serum 30 g/l). Electrochemical measurements were made using a potentiostat. Samples then undergo 3600 cycles at 50 µm (to simulate gross slips), with a horizontal load at 200 N, and a frequency of 0.5 Hz, 0.7 Hz, 1 Hz, and 1.5 Hz to simulate Sit Down-Stand Up, Stair Climb, Walking, and Jogging, respectively. Worn surfaces were then examined under optical and scanning electron microscopy. The evolution of free potential as a function of time for tested frequencies shows the initial potential drop and stabilized trend in the potential evolution. The sample group at a higher frequency displays a higher tendency of corrosion than a lower frequency; however, the dissipation energy decreases as a function of fretting frequency. Both electrochemical and mechanical responses correlate to the variation in the fretting frequencies. Organometallic complexes were found on the surfaces of the samples that were subjected to a slower frequency of fretting, whereas mechanical grooving was noticed on samples with a faster frequency. Hence, these preliminary studies suggest that implant failure rates may be altered based on fretting-frequencies induced by physical activity. Further studies will be required to verify the findings and explore the potential role of fretting frequency in the damage modes of the modular junction.

Non-invasive early detection of failure modes in total hip replacements (THR) via acoustic emission (AE).

Total hip replacements (THR) are becoming an common orthopedic surgucal procedure in the United States (332 K/year in 2017) to relieve pain and improve the mobility of those that are affected by osteoarthritis, ankylosing spondylitis, or injury. However, complications like tribocorrosion, or material degradation due to friction and corrosion, may result in THR failure. Unfortunately, few strategies to non-invasively diagnose early-stage complications are reported in literature, leading to implant complications being detected after irreversible damage. Therefore, the main objective of this study proposes the utilization of acoustic emission (AE) to continuously monitor implant materials, CoCrMo and Ti6Al4V, and identify degradations formed during cycles of sleeping, standing, and walking by correlating them to potential and friction coefficient behavior. AE activity detected from the study correlates with the friction coefficient and open-circuit potential observed during recreated in-vitro standing, walking, and sleeping cycles. It was found that the absolute energy level obtained from AE increased as the friction coefficient increased, potential decreased, and wear volume loss increased. Through the results, higher friction coefficient and AE activity were observed in Ti6Al4V alloys while there was also a significant drop in potential, indicating increased tribocorrosion activity. Therefore, AE can be utilized to predict material degradations as a non-invasive method based on the severity of abnormality of the absolute energy and hits emitted. The correlation between potential, friction coefficient, and AE activity was further confirmed through profilometry which showed more material degradation in Ti6Al4V than CoCrMo. Through these evaluations, it was demonstrated that AE could be utilized to identify the deformations and failure modes of implant materials caused by tribocorrosion.

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

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 (MCA 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. MCA cells also secreted higher levels of IL-8, IL-1ß, IL-6, IL-10, TNF-α, and IL-12p70 than M1 macrophages and/or M2 macrophages. Our findings revealed variation in macrophage phenotype (MCA) induced by CoCrMo wear particles in generating a chemical environment that induces cell-accelerated corrosion of CoCrMo alloy at THR modular interfaces. STATEMENT OF SIGNIFICANCE: Fretting wear and corrosion within the implant's modular taper junction are prominent causes of implant failure, as they promote the release of corrosion products and subsequent development of adverse local tissue reactions. Being a multifactorial process, several in vitro models have been developed to recreate the in vivo corrosion process, often summarized as mechanically-assisted crevice corrosion. Considering the excellent corrosion properties of CoCrMo alloy, the severity of chemically-generated damage observed at the modular interface has been surprising and poorly understood. The aim of the current study is to provide a better understanding of macrophages and their plasticity at the THR taper interface when they encounter wear debris from CoCrMo alloy. This is a preliminary study along the path towards determining the mechanism(s) of CAC.

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

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.

Comparison of metal ion levels in patients with hip resurfacing versus total hip arthroplasty.

Mechanical wear at the articular surface and corrosive processes at modular junctions, such as the trunnion, are responsible for metal ions production. We retrospectively reviewed 64 patients who underwent THA with a metal on metal bearing surface and 34 patients with hip Resurfacing. Metal ion measurements, six-week post-op radiographs, and functional scores were included in the analysis. Cobalt ion levels were significantly elevated in THA patients, 2.95 µg/L as compared to resurfacing patients, (2.95 versus 1.30 µg/L, p < 0.0005). Chromium levels were not significantly different between THA patients and resurfacing patients (1.05 versus 1.00 µg/L, p = 0.529).