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

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.

The Expression Levels of Toll-like Receptors after Metallic Particle and Ion Exposition in the Synovium of a Murine Model

“…Additionally, the aspect ratio (AR), equivalent circular diameter (ECD), and the roundness (R) of wear particles were determined utilizing scanning electron microscopy (SEM; Carl Zeiss, Oberkochen, Germany). According to our previous results, these generated particles have a mean size in the nanometer range (ECD: 61.25 ± 18.47 nm) with an aspect ratio of 1.69 ± 0.66 and a roundness of 0.64 ± 0.16 [34]. Additionally, the shape of metal particles was principally round and oval, accompanied by a small proportion of needle-shaped particles, similar to wear particles in retrieved tissues of revision surgeries [35,36].…”

The Mechanisms Underlying the Biological Response to Wear Debris in Periprosthetic Inflammation

“…However, in a study using a mouse model, the intraarticular injection of CoCrMo particles induced a significantly enhanced pro-inflammatory cytokine expression (TNF-α, IL-6, and IL-1β) when compared to the intraarticular injection of CoCrMo ions (Cheng et al, 2020). On the other hand, the expression of CD3-positive cells in the synovial membrane of mouse knee did not increase in any of the groups (Cheng et al, 2020). In the same line, data from an epidemiologic study showed that patients with MoM or MoP implants displayed a decrease in blood T lymphocytes despite an increase in the serum level of chromium and cobalt (Granchi et al, 2003).…”

“…The activation of macrophage by cobalt-alloy particles resulted in a T helper 17 (Th17) cell inflammatory response, which is directly associated with the risk of osteolysis development (Chen et al, 2017). However, in a study using a mouse model, the intraarticular injection of CoCrMo particles induced a significantly enhanced pro-inflammatory cytokine expression (TNF-α, IL-6, and IL-1β) when compared to the intraarticular injection of CoCrMo ions (Cheng et al, 2020). On the other hand, the expression of CD3-positive cells in the synovial membrane of mouse knee did not increase in any of the groups (Cheng et al, 2020).…”

<p>Bacterial Biofilm Components Induce an Enhanced Inflammatory Response Against Metal Wear Particles</p>

“…In an earlier study, the current pin-on-plate setup including the lubricant has been found to produce particles which are comparable in size and morphology to clinically produced metal particles in joint revision. 30…”