Particulate and ion forms of cobalt–chromium challenged preosteoblasts promote osteoclastogenesis and osteolysis in a murine model of prosthesis failure

Abstract

This study investigated the interactive behavior of the particulate and ion forms of Cobalt-Chromium (Co-Cr) alloy challenged preosteoblasts during the process of prosthetic implant loosening. Preosteoblasts were challenged with Co-Cr particles or Co(II) ions for 72 hours, followed by the proliferation and PCR assays. For in vivo test, a titanium-pin was implanted into proximal tibia of SCID mice to mimic knee replacement. Co-Cr particles or Co(II) ion challenged preosteoblasts (5×105) were intra-articularly injected into the implanted knee. The animals were sacrificed 5 weeks post-op, and the prosthetic knees were harvested for biomechanical pin-pullout testing, histological evaluations, and microCT assessment. In vitro study suggested that Co-Cr particles and Co(II) ions significantly suppressed the proliferation of preosteoblasts in a dose-dependent manner. RT-PCR data on the challenged cells indicated over-expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and inhibited osteoprotegerin (OPG) gene expression. Introduction of the differently challenged preosteoblasts to the pin-implant mouse model resulted in reduced implant interfacial shear strength, thicker peri-implant soft-tissue formation, more TRAP+ cells, lower bone mineral density and bone volume fraction. In conclusion, both Co-Cr particles and Co(II) ions interfered with the growth, maturation and functions of preosteoblasts, and provides evidence that the metal ions as well play an important role in effecting preosteoblasts in the pathogenesis of aseptic loosening.

The Mechanism of Metallosis After Total Hip Arthroplasty

“…3). Genetics, lifestyles, allergies, preexisting ailments, acquired metal sensitivity and allergy, female gender, individuals with bilateral hip/knee implants, obesity, underweight, renal insufficiencies/failures, and highly physical jobs that require heavy lifting have all been implicated in the mechanism of metallosis [9,12,26,29].…”

“…However, wear particles alone can be recognized as antigens in certain instances [43]. The uptake of particulate metal debris by macrophages through phagocytosis is a key process by which implants may trigger inflammatory responses leading to metallosis [28,29,44]. After macrophages identify particles through pattern recognition receptors, including toll-like receptor, retinoid acid-inducible gene-1-like receptors, aim 2-like receptor, and nucleotide-binding oligomerization domain-like receptors, they form a cascade of reactions generating pro-inflammatory cytokines, including interleukin-1β, interleukin-6, interleukin-18, and tissue necrosis factor-α, as well as the chemokines (CXCL8, CCL2, and CCL3), and other small molecule inflammatory mediators [31,42].…”

The effect of nanoparticles of cobalt–chromium on human aortic endothelial cells in vitro

“…In addition, metal ions (Co ions) can regulate adhesion of inflammatory cells such as neutrophils to endothelial cells (Wagner et al, 1998). It has also been reported that the presence of CoCr particles resulted in greater inflammatory response (Yang et al, 2019). The dysregulation of endothelial cells and activation of inflammatory response could increase the expression of proinflammatory cytokines and active metalloproteinase, affecting the microenvironment around the corroded stents, possibly leading to the development of ISR.…”

“…Moreover, CoCr particles in range of nanometer to micrometer have been used to investigate their effect on the various types of cells, for example, fibroblasts. It has been demonstrated that CoCr particles can not only lead to the DNA damage in human fibroblasts (Papageorgiou, Brown, et al, 2007; Papageorgiou, Yin, et al, 2007; Tsaousi et al, 2010), but also can interfere with the growth, maturation and function of preosteoblasts (Yang et al, 2019). It was reported that clinically relevant CoCr NPs caused significant changes in the structural integrity of the dura mater, which may lead to significant secondary effects, such as local nerve tissue inflammation (Papageorgiou et al, 2014).…”

Corrosion of Metals During Use in Arthroplasty

“…Corrosion involves the gradual destruction of materials by electrochemical reactions within their environment. , It is an exothermic process involving electrochemical degradation of metallic materials, propelled by the thermodynamics of a metal shift toward a low energy (chemical) potential, which usually takes place as an electron flows from the anodic region to the cathode . Corrosion occurs basically via three distinct stages of events: (1) Ions from the metal surface dissolve in oxidation in the electrochemical active surrounding releasing cations.…”