In vitro evaluation of human myoblast function after exposure to cobalt and chromium ions

Abstract

The replacement of a native hip joint by a metal‐on‐metal prosthesis may induce deleterious inflammatory side effects that are associated with the release of wear particles and metal ions. These events are referred to the adverse reaction to metal debris (ARMD) and the adverse local tissue reaction (ALTR). While wear particles seem involved in ARMD, the role of metal ions in ALTR and their impact on myoblasts, located in the prosthesis vicinity, has not been fully identified. To clarify this issue we investigated, using an in vitro culture system, the effect of cobalt and/or chromium ions (Co2+ and/or Cr3+) on human myoblast proliferation, cellular differentiation, and inflammatory marker expression. Freshly isolated human myoblasts were cultured in media supplemented with graded concentrations of Co2+ and/or Cr3+. Co2+ induced a concentration‐dependent decrease of both myoblast viability and myogenic differentiation while Cr3+ did not. Co2+ or Co2+/Cr3+ also induced the upregulation of ICAM‐1, whereas HLA‐DR expression was unaffected. Moreover, allogenic monocytes induced the synergistic increase of Co2+‐induced ICAM‐1 expression. We also found that Co2+ stabilized HIF‐1α and increased TLR4, tumor necrosis factor‐alpha (TNF‐α), and interleukin 1β (IL‐1β) expression in a dose and time‐dependent manner in human myoblasts. This study showed that Co2+, but not Cr3+, was toxic toward myoblasts and induced, in the surviving cells, expression of inflammatory markers such as ICAM‐1, TLR4, TNF‐α, and IL‐1β. This suggests that Co2+, most efficiently in the presence of monocytes, may be a key inducer of ALTR, which may, if severe and long‐lasting, eventually result in prosthesis loosening.

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All‐Poly acetabular cup

“…Metal ions can be released by multiple mechanisms: (a) wear‐mediated disruption of the passive layer on the implant surface, (b) release of metal ions from nano‐ and micron‐sized particles in body fluids, (c) cellular reactions—especially in the lysosomes—to the phagocytized particles generate metal ions that can be released into the periprosthetic tissue 25 . Several studies have shown the inflammatory and osteolytic effect of cobalt and chromium ions 30,31 . The presence of elevated metal ions in synovial fluid and serum has been associated with the development of adverse local reactions in periprosthetic tissue 32 .…”

“…25 Several studies have shown the inflammatory and osteolytic effect of cobalt and chromium ions. 30,31 The presence of elevated metal ions in synovial fluid and serum has been associated with the development of adverse local reactions in periprosthetic tissue. 32 A previous study demonstrated a strong correlation between elevated metal ion concentrations and patients with ALTR.…”

Fe and C additions decrease the dissolution rate of silicon nitride coatings and are compatible with microglial viability in 3D collagen hydrogels

“…This cytotoxicity has been observed in various cell types, including human cell lines and primary cells. 57,58 Nonetheless, since CoCrMo is an established material used in spinal implants, obtaining a comparable cell viability with the extracts from the SiFeCN coatings is considered a promising result, indicating that further evaluation of these materials is warranted.…”

Ceramic‐on‐polyethylene hip arthroplasty reduces the risk of postoperative periprosthetic joint infection

“…These metal ions are increasingly recognized as both local and systemic toxins based on the alterations to native host tissues they produce and due to the increased migration of T lymphocytes caused by Co and Cr ions. [8][9][10] There is evidence that the local toxicity of these ions is associated with adverse local tissue reaction (ALTR), adverse reaction to metal debris (ARMD), inflammatory pseudotumor, and local osteolysis. 11,12 Although these diseases may partly explain the higher revision rates of MoP prosthesis, no conclusive evidence exist on the risk of PJI associated with these implants.…”