Periprosthetic osteolysis: Characterizing the innate immune response to titanium wear‐particles

Pierre, Christine A. St.; Chan, Melvin; Iwakura, Yoichiro; Ayers, David C.; Kurt-Jones, Evelyn A.; Finberg, Robert W.

doi:10.1002/jor.21149

Cited by 116 publications

(75 citation statements)

References 41 publications

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“…Ti particles have been repeatedly reported to induce an inflammatory response in vivo in the tissue surrounding implants and in vitro 111314. However, the pro-inflammatory response to the particles that originated from the ultrasonic scaling of dental implants has not yet been studied.…”

Section: Resultsmentioning

confidence: 99%

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Scaling of titanium implants entrains inflammation-induced osteolysis

Eger

Sterer

Liron

et al. 2017

Sci Rep

100

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With millions of new dental and orthopedic implants inserted annually, periprosthetic osteolysis becomes a major concern. In dentistry, peri-implantitis management includes cleaning using ultrasonic scaling. We examined whether ultrasonic scaling releases titanium particles and induces inflammation and osteolysis. Titanium discs with machined, sandblasted/acid-etched and sandblasted surfaces were subjected to ultrasonic scaling and we physically and chemically characterized the released particles. These particles induced a severe inflammatory response in macrophages and stimulated osteoclastogenesis. The number of released particles and their chemical composition and nanotopography had a significant effect on the inflammatory response. Sandblasted surfaces released the highest number of particles with the greatest nanoroughness properties. Particles from sandblasted/acid-etched discs induced a milder inflammatory response than those from sandblasted discs but a stronger inflammatory response than those from machined discs. Titanium particles were then embedded in fibrin membranes placed on mouse calvariae for 5 weeks. Using micro-CT, we observed that particles from sandblasted discs induced more osteolysis than those from sandblasted/acid-etched discs. In summary, ultrasonic scaling of titanium implants releases particles in a surface type-dependent manner and may aggravate peri-implantitis. Future studies should assess whether surface roughening affects the extent of released wear particles and aseptic loosening of orthopedic implants.

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Section: Resultsmentioning

confidence: 99%

“…This inflammation is thought to be caused by the Ti particles that are released from the implant surface into the surrounding micro-environment, where they are phagocytosed by circulating monocytes and macrophages1011. Macrophages engulf Ti particles causing them to secrete inflammatory cytokines, such as IL1β, IL6 and TNFα.…”

mentioning

confidence: 99%

Scaling of titanium implants entrains inflammation-induced osteolysis

Eger

Sterer

Liron

et al. 2017

Sci Rep

100

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“…Previous studies have reported that titanium particles trigger neutrophil recruitment in an IL-1α/β dependent manner [33]. In addition, when neutrophils were exposed to UHMWPE particles, there was a significant correlation between the bactericidal activity of neutrophils with the number and size of the particles [34].…”

Section: Discussionmentioning

confidence: 99%

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: A preliminary report

et al. 2014

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Total joint replacement (TJR) is a very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate especially because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to peri-prosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical trials, due to compensatory upregulation of other pro-inflammatory factors. We hypothesized that targeting the important transcription factor NF-κB could mitigate the inflammatory response to wear particles, potentially diminishing osteolysis. In the current study, we suppressed NF-κB activity in mouse RAW264.7 and human THP1 macrophage cell lines, as well as primary mouse and human macrophages, via competitive binding with double strand decoy oligodeoxynucleotide (ODN) containing an NF-κB binding element. We found that macrophage exposure to UHMWPE particles induced multiple pro-inflammatory cytokine and chemokine expression including TNF-α, MCP1, MIP1α and others. Importantly, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, and resulted in suppression of macrophage recruitment. The strategic use of decoy NF-κB ODN, delivered locally, could potentially diminish particle-induced peri-prosthetic osteolysis.

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“…It has previously been shown that particle size is crucial for the induced pro‐inflammatory response 23, 24, 51. Image analysis showed that serum proteins are needed for aggregate formation, and when Co was added, aggregates were larger, but fewer than those formed by Ti alone.…”

Section: Discussionmentioning

confidence: 96%

Effect of cobalt ions on the interaction between macrophages and titanium

Pettersson

Thorén

et al. 2018

J Biomedical Materials Res

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Inflammation and bone reduction around dental implants are described as peri‐implantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL‐1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro‐inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP‐1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL‐1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy and electron microscopy. Co at a concentration of 100 µM neutralized the IL‐1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti‐induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti‐induced activation and release of active IL‐1β from human macrophages in vitro. Also, serum proteins are needed for the formation of metal‐protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localisation after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seen in vitro with Ti present, were also visible in a sample from human peri‐implant tissue. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2518–2530, 2018.

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Periprosthetic osteolysis: Characterizing the innate immune response to titanium wear‐particles

Cited by 116 publications

References 41 publications

Scaling of titanium implants entrains inflammation-induced osteolysis

Scaling of titanium implants entrains inflammation-induced osteolysis

Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-κB decoy oligodeoxynucleotide: A preliminary report

Effect of cobalt ions on the interaction between macrophages and titanium

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