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

ABSTRACT: 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-?, 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-1?, IL-6, IL-10, TNF-?, 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.

SUBMITTER: Bijukumar DR

PROVIDER: S-EPMC7370988 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Bijukumar Divya Rani DR Salunkhe Shruti S Zheng Guoxing G Barba Mark M Hall Deborah J DJ Pourzal Robin R Mathew Mathew T MT

Acta biomaterialia 20191031

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 w ...[more]

PMID: 31678260

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Project description:Multinucleate giant cells (MGCs) are formed by the fusion of 5 to 15 monocytes or macrophages. MGCs can be generated by hip implants at the site where the metal surface of the device is in close contact with tissue. MGCs play a critical role in the inflammatory processes associated with adverse events such as aseptic loosening of the prosthetic joints and bone degeneration process called osteolysis. Upon interaction with metal wear particles, endothelial cells upregulate pro-inflammatory cytokines and other factors that enhance a localized immune response. However, the role of endothelial cells in the generation of MGCs has not been completely investigated. We developed a three-dimensional peripheral tissue-equivalent model (PTE) consisting of collagen gel, supporting a monolayer of endothelial cells and human peripheral blood mononuclear cells (PBMCs) on top, which mimics peripheral tissue under normal physiological conditions. The cultures were incubated for 14 days with Cobalt chromium alloy (CoCr ASTM F75, 1-5 micron) wear particles. PBMC were allowed to transit the endothelium and harvested cells were analyzed for MGC generation via flow cytometry. An increase in forward scatter (cell size) and in the propidium iodide (PI) uptake (DNA intercalating dye) was used to identify MGCs. Our results show that endothelial cells induce the generation of MGCs to a level 4 fold higher in 3-dimentional PTE system as compared to traditional 2-dimensional culture plates. Further characterization of MGCs showed upregulated expression of tartrate resistant alkaline phosphatase (TRAP) and dendritic cell specific transmembrane protein, (DC-STAMP), which are markers of bone degrading cells called osteoclasts. In sum, we have established a robust and relevant model to examine MGC and osteoclast formation in a tissue like environment using flow cytometry and RT-PCR. With endothelial cells help, we observed a consistent generation of metal wear particle- induced MGCs, which heralds metal on metal hip failures.

Project description:WHERE ARE WE NOW?: Biological treatments, defined as any nonsurgical intervention whose primary mechanism of action is reducing the host response to wear and/or corrosion products, have long been postulated as solutions for osteolysis and aseptic loosening of total joint arthroplasties. Despite extensive research on drugs that target the inflammatory, osteoclastic, and osteogenic responses to wear debris, no biological treatment has emerged as an approved therapy. We review the extensive preclinical research and modest clinical research to date, which has led to the central conclusion that the osteoclast is the primary target. We also allude to the significant changes in health care, unabated safety concerns about chronic immunosuppressive/antiinflammatory therapies, industry's complete lack of interest in developing an intervention for this condition, and the practical issues that have narrowly focused the possibilities for a biologic treatment for wear debris-induced osteolysis. WHERE DO WE NEED TO GO?: Based on the conclusions from research, and the economic, regulatory, and practical issues that limit the future directions toward the development of a biologic treatment, there are a few rational approaches that warrant investigation. These largely focus on FDA-approved osteoporosis therapies that target the osteoclast (bisphosphonates and anti-RANK ligand) and recombinant parathyroid hormone (teriparatide) prophylactic treatment to increase osseous integration of the prosthesis to overcome high-risk susceptibility to aseptic loosening. The other roadblock that must be overcome if there is to be an approved biologic therapy to prevent the progression of periprosthetic osteolysis and aseptic loosening is the development of radiological measures that can quantify a significant drug effect in a randomized, placebo-controlled clinical trial. We review the progress of volumetric quantification of osteolysis in animal studies and clinical pilots. HOW DO WE GET THERE?: Accepting the aforementioned rigid boundaries, we describe the emergence of repurposing FDA-approved drugs for new indications and public (National Institutes of Health, FDA, Centers for Disease Control and Prevention) and private (universities and drug and device manufactures) partnerships as the future roadmap for clinical translation. In the case of biologic treatments for wear debris-induced osteolysis, this will involve combined federal and industry funding of multicenter clinical trials that will be run by thought leaders at large medical centers.

Dataset Information

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

Publications

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

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