Biological Reactions to Metal Particles and Ions in the Synovial Layer of Mice.

Xiangyun Cheng,Sabine C Dirmeier,Alexander C Paulus,Sandra Utzschneider,Andrea Baur-Melnyk,Sandra Haßelt,Rainer Bader,Jan Philippe Kretzer

doi:10.3390/ma13051044

Abstract

Metal particles and ions released from implants not only have a fundamental effect on the longevity of total joint replacements, but can also be disseminated to remote organs. Periprosthetic tissues harvested during revision surgeries mainly reflect end-stage failure but may not adequately reveal initial biological reactions and systemic side effects. Therefore, primary reactions caused by metal particles and ions were investigated in an established murine model. Left knee joints in three groups, each consisting of ten female BALB/c mice, received injections of metal ions (MI), metal particles (MP) and phosphate-buffered saline (PBS) (control). Seven days after the injection, immunohistochemical analyses of the synovial layer were performed with respect to some biological markers including Tumor necrosis factor -α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Cluster of Differentiation 45 (CD45), Cluster of Differentiation 68 (CD68) and Cluster of Differentiation 3(CD3). The MP group showed significantly enhanced proinflammatory cytokine expression (TNF-α, IL-6 and IL-1β) compared with the other groups (p < 0.05). Interestingly, CD3, as a marker for T lymphocytes, did not increase in any of the groups. The MI group showed a significantly increased expression of CD45 compared with the control group (p < 0.05). Therefore, during the primary process, metal particles have stronger pro-inflammatory potential than metal ions, and T lymphocytes did not seem to be activated in our murine model. Systemic reactions caused by metal particles and ions were found by observing the untreated right knees.

Highlights

Medical cobalt-chromium-molybdenum (CoCrMo) alloys are mainly classified by the InternationalOrganization for Standardization (ISO) or American Society for Testing and Materials (ASTM) [1]and can be of a cast (ASTM F75, InternationalOrganization for Standardization (ISO) 5832-4) or wrought content (ASTM F1537, ISO 5832-12) [2,3].Materials 2020, 13, 1044; doi:10.3390/ma13051044 www.mdpi.com/journal/materialsDue to their excellent biocompatibility and mechanical properties, these alloys have been widely employed in implant devices that replace hard tissue in the human body [4]
With regard to the staining results of Tumor necrosis factor -α (TNF-α), IL-1β and IL-6, the metal particles (MP) group showed a significantly increased number of positive cells compared with the phosphate-buffered saline (PBS) group (p < 0.05)
Considering that of TNF-α, IL-1β and IL-6 macrophages play an important role in inflammatory reactions, these results indicate that the MP

Summary

Introduction

Due to their excellent biocompatibility and mechanical properties, these alloys have been widely employed in implant devices that replace hard tissue in the human body [4]. During the 2000s, issues of aseptic loosening due to the release of metal particles and ions were found, and the use of MoM replacements was almost completely stopped [6]. The generation of degradation products and the subsequent biological reactions to the metal particles and ions have a fundamental effect on the longevity of total joint replacement [10]. To date, the effects of small wear particles and metal ions on local or systemic biological reactions remain complex and are still not fully understood in detail

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