The role of Vitamin E in hip implant-related corrosion and toxicity: Initial outcome

Highlights

• To our knowledge, this is the first study reported on the dual role of Vitamin E as a corrosion and cytotoxicity inhibitor.

• Results showed 91 ± 3% corrosion inhibition efficiency by Vitamin E-protein complex compared to Vitamin E alone (45 ± 0.9%).

• The alteration in DNA replication dynamics induced by wear particles returned to normal level in the presence of Vitamin E.

• Vitamin E minimizes the corrosion processes and potential toxicity associated with metallic implants.

Abstract

In orthopedic healthcare, Total Hip Replacement (THR) is a common and effective solution to hip-related bone and joint diseases/fracture; however, corrosion of the hip implant and the release of degradation metal ions/particles can lead to early implant failure and pose potential toxicity risk for the surrounding tissues. The main objective of this work was to investigate the potential role of Vitamin E to minimize corrosion-related concerns from CoCrMo hip implants. The study focused on two questions (i) Can Vitamin E inhibit CoCrMo corrosion? and (ii) Does Vitamin E moderate the toxicity associated with the CoCrMo implant particles?

In the study (i) the electrochemical experiments (ASTM G61) with different concentrations of Vitamin E (1, 2, 3 mg/ml against the control) were performed using normal saline and simulated synovial fluid (Bovine calf serum-BCS, 30 g/L protein, pH 7.4) as electrolytes. The polished CoCrMo disc (Ra 50 nm) was the working electrode. The findings suggested that both Vitamin E-Saline (45 ± 0.9%) and Vitamin E-BCS (91 ± 3%) solutions protected against implant corrosion at a Vitamin E concentration of 3 mg/ml, but Vitamin E-BCS showed protection at all Vitamin E (1-3 mg/ml) concentration levels. These results suggested that the Vitamin E and the protein present in the BCS imparted additive effects towards the electrochemical inhibition.

In the study (ii) the role of Vitamin E in cytotoxicity inhibition was studied using a mouse neuroblastoma cell line (N2a) for CoCrMo particles and Cr ions separately. The CoCrMo particles were generated from a custom-built hip simulator. The alamarBlue assay results suggested that Vitamin E provides significant protection (85% and 75% proliferation) to N2a cells against CoCrMo particles and Cr ions, respectively at 1 μg/ml concentration, as compared to the control group. However, the results obtained from ROS expression and DNA fiber staining suggest that Vitamin E is only effective against CoCrMo degradation particles and not against Cr ions.

In summary, the findings show that Vitamin E can minimize the corrosion processes and play a role in minimizing the potential toxicity associated with implants.

Introduction

Total Hip Replacement (THR) is the end-stage treatment option when all conservative treatments fail to relieve the problems of pain, stiffness, and loss of function associated with osteoarthritis, rheumatoid arthritis, osteonecrosis, or traumatic injury of the hip joint. As per the American Joint Replacement Registry (AJRR) 2019 report, around 332K primary THRs were performed annually in the United States (Stibolt et al., 2018). The significant increase in the number of THRs along with an aging population and increased prevalence of obesity, suggests an increasing future demand for this treatment (Program, n.d.; Sloan et al., 2018; Zhai et al., 2019).

Retrieval studies and case reports have shown that corrosion and/or corrosion accelerated wear (tribocorrosion/mechanically assisted crevice corrosion (MACC)) are important causes of hip implant failure (Eliaz, 2019; Mathew et al., 2010; Runa et al., 2017). In addition, tribocorrosion of the implant releases degradation particles, which include wear particles and metal ions. These particles may react with local moieties to form metal salts, colloidal organometallic complexes, or protein-coated micro- or nano-particulate debris. Previous studies have provided clear evidence of the toxicity of degradation products in the periprosthetic tissue, causing adverse local tissue reactions (ALTRs) such as necrosis, osteolysis, pseudotumor formation, and aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) which can necessitate revision surgery (Ricciardi et al., 2016; Sansone et al., 2013). For many older patients, revision surgery is impractical, risky, and exposes them to additional morbidity, including periprosthetic joint infection; avoidance of revision surgery is a primary goal of total hip replacement.

Systemic toxicity of degradation products when they travel to remote areas of the body through the lymphatic and systemic circulatory systems is an active area of investigation. Studies on blood and tissue samples of THR patients have reported the deposition of metal particles in distal organs, such as the liver, spleen, kidneys, and heart (Bijukumar et al., 2018b; Urban et al., 2000). The primary particles associated with wear and tribocorrosion of THR are Co and Cr particles and metal ions. The particles can range from nanometers to micrometers in size. In turn, these particles can generate metal ions, which can complex with local moieties to form metal/protein complexes. These particles have been implicated in a variety of toxicities, such as polyneuropathy with progressive sensory disturbances, hypothyroidism, hearing and vision loss, cardiomyopathy, polycythemia, and fatigue (Back et al., 2005; Devlin et al., 2013; Green et al., 2017; Peters et al., 2017). The gradual increase in toxicity-related complications associated with particles in THR patients could become a significant clinical problem in orthopedics (“Biological Responses to Metal Implants,” n.d. 2019). As the number of THR patients continues to grow, and with more young people receiving implants with higher expectations for physical activity and longevity, methods for limiting corrosion and wear as well as treating local and systemic toxicity are essential in minimizing the need for revision surgeries and preventing particle-associated morbidity.

Techniques that have been shown to be effective in reducing corrosion in complex bio-systems include implant surface chemical treatment, plasma source ion implantation (PSII), laser nitration, ion implantation, plasma ion implantation, laser melting (LSM), texturing, physical vapor deposition (PVD), and adjusting the wettability of the surface (Kumar et al., 2009; Kurella and Dahotre, 2005; Liu et al., 2016; Singh and Dahotre, 2007). One method which garnered much attention is the use of non-toxic corrosion inhibitors. Various compounds such as azoles, proteins, polyacrylamides, lipopolysaccharides, dextrose, laurate, chlorhexidine gluconate, and vitamin C have previously been studied for their anti-corrosion properties, primarily for industrial applications (Bhola et al., 2013; Faverani et al., 2014; Shibli and Saji, 2002). These anti-corrosion properties are observed mainly due to characteristic structural features and functional groups with high electro-negativity, such as those containing sulfur, oxygen, and nitrogen. Vitamin C, a potent biological antioxidant, was reported to possess strong corrosion inhibition properties (Fuchs et al., 2013). Although it was reported that corrosion inhibitors could not be used in extremely sensitive and complex bio-systems, many studies are reporting on the efficacy of corrosion inhibitors in in-vitro implant models (Manivasagam et al., 2010; Vieira et al., 2006; Winkler, 2017). The literature has also revealed that vitamin E, another powerful biological antioxidant, was also considered for its corrosion resistance activity (Al-Attar, 2011; Niki, 2015; Valko et al., 2005; Zagra and Gallazzi, 2018). There are reports that vitamin E (alone or with vitamin C) also protects against the local and systemic toxicities caused by the free radicals and reactive oxygen species (ROS) generated by particles (Birben et al., 2012; Free radicals, natural antioxidants, and their reaction mechanisms - RSC Advances (RSC Publishing) n.d.; Kurutas, 2016; Packer et al., 1979; Yan et al., 2018). In this study, the efficacy of vitamin E in protecting against corrosion and toxicity from hip implants fabricated from cobalt-chromium-molybdenum alloy (CoCrMo) was evaluated. Corrosion inhibition by vitamin E was studied using a custom-built corrosion simulator (Butt et al., 2015) in two different corrosion mediums (normal saline and simulated synovial fluid).

Along with local toxicities (ALTR), there are many reports of systemic toxicity due to different metal ions and particles generated from metal implants (Ricciardi et al., 2016; Bijukumar et al., 2018b). There are several reports of neurological symptoms in the MoM THR patients which were suspected due to systemic toxicity of cobalt and chromium ions generated from metal-on-metal hip implants (Queally et al., 2009). In this study, the N2a cell lines were used as representative cells to correlate the systemic toxicity and neurological symptoms. Hence, the toxicity protection studies were conducted on a mouse neuroblastoma cell line (N2a) using particles (CoCrMo) generated from the custom-built corrosion simulator, as well as commercially-obtained Cr ions in the form of Cr₂O₆. Thus, this study explores the possibility of using vitamin E both as a non-toxic implant corrosion inhibitor as well as a local and systemic particles toxicity inhibitor.