The role of Vitamin E in hip implant-related corrosion and toxicity: Initial outcome
Graphical abstract
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.
Section snippets
Materials
In this study, a CoCrMo alloy sample in the form of a disc (11 mm diameter and 7 mm thickness) was used as the working electrode. A total of 24 discs were milled from CoCrMo alloy rods (MacMaster Carr, Elmhurst, Illinois, USA), which were then divided into 8 groups (n = 3). Each disc was first wet ground with 320–800 grit silicon carbide paper (Carbimet 2, Buehler, Lake Bluff, Illinois, USA) and then further polished with a polishing cloth, diamond paste, and lubricant (TextMet cloth and MetaDi
Electrochemical characterization
The electrochemical data were used to construct the potentiodynamic curves for vitamin E-saline (1, 2, and 3 mg/ml alpha-tocopherol emulsified in saline using 15% w/v Tween80) and vitamin E-BCS (1, 2, and 3 mg/ml alpha-tocopherol emulsified in saline-bovine calf serum (BCS-30 g/L) using 15% w/v Tween80) are shown in Fig. 2(a&b), respectively, and they are very distinct from each other. The Icorr values observed for CoCrMo corrosion in vitamin E-saline were in current densities ranging between
Discussion
This study was intended to explore the role of vitamin E in both the corrosion inhibition of THR implants as well as protection against cell toxicity related to the degradation particles generated from implant corrosion/tribocorrosion. Both electrochemical studies and surface topography studies provided evidence that vitamin E in the presence of proteins in the electrolyte generates a protective layer on the implant surface, which reduces the rate of corrosion. It was also observed that vitamin
Conclusions
With the limited experimental results from this study, the following conclusions can be derived. This study demonstrated the role of vitamin E in protecting against CoCrMo corrosion in the custom-built corrosion simulator as well as in inhibiting cell toxicity. From the electrochemical results obtained, it is evident that vitamin E, in combination with proteins in BCS, supports a protective film formation on the CoCrMo surface and inhibits corrosion. Because its interaction with proteins
Author statement
M.T.M, D.B, E.O: Conceptualization, methodology, supervision; V.M., M.M, J.R, A.B, A.S: Investigation, writing-review. P.C, D.B. R.V.B, and M.T.M: validation, supervision P.C. supervision (DNA fiber analysis). J.J.J. Supervision (clinical guidance and feedback on experimental designs). V.M., P.C., R.V.B, D.B., and M.T.M: Writing, review & editing. M.T.M & D.B: Funding acquisition.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
The authors acknowledge financial support from the Blazer Foundation for Regenerative Medicine and Disability Research and Nanomedicine Labs at the Department of Biomedical Sciences, UIC College of Medicine at Rockford. The authors also acknowledge NIH R01 - AR070181, NIH R03 - R03NS111554 and Department of Health Science Education (UIC-Rockford) funding for financial support. The authors sincerely acknowledge the technical and intellectual support provided by UICCOM-Rockford and Harris
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