Background and ObjectivePeri‐implantitis is a destructive inflammatory process characterized by destruction of the implant‐supporting bone. Inflammasomes are large intracellular multiprotein complexes that play a central role in innate immunity by activating the release of proinflammatory cytokines. Although inflammasome activation has previously been linked to periodontal inflammation, there is still no information on a potential association with peri‐implantitis. The aim of this study was to examine cytotoxic and proinflammatory effects, including inflammasome activation, of metals used in dental implants, in an in vitro model, as well as from clinical tissue samples.Material and methodsHuman macrophages were exposed to different metals [titanium (Ti), cobalt, chromium and molybdenum] in a cell‐culture assay. Cytotoxicity was determined using the neutral red uptake assay. Cytokine secretion was quantified using an ELISA, and the expression of genes of various inflammasome components was analysed using quantitative PCR. In addition, the concentrations of interleukin‐1β (IL‐1β) and Ti in mucosal tissue samples taken in the vicinity of dental implants were determined using ELISA and inductively coupled plasma mass spectrometry, respectively.ResultsTi ions in physiological solutions stimulated inflammasome activation in human macrophages and consequently IL‐1β release. This effect was further enhanced by macrophages that have been exposed to lipopolysaccharides. The proinflammatory activation caused by Ti ions disappeared after filtration (0.22 μm), which indicates an effect of particles. Ti ions alone did not stimulate transcription of the inflammasome components. The Ti levels of tissue samples obtained in the vicinity of Ti implants were sufficiently high (≥ 40 μm) to stimulate secretion of IL‐1β from human macrophages in vitro.ConclusionTi ions form particles that act as secondary stimuli for a proinflammatory reaction.

Since the discovery of osseointegration in the 1960s by Per-Ingvar Brånemark, 1 dental titanium (Ti) implants have been widely used as a standard treatment for edentulism. An estimated 5 million implants are placed annually in the United States, and a total of 15-20 million implants are placed worldwide. 2,3 Long-term follow-up studies show that implant usage to replace missing or lost teeth is a safe and predictable treatment with an overall 5-year survival rate of 98.1% for the implants and 97.1% for the prosthetics. 4 However, researchers and dentists are concerned about the rising number of published reports on inflammatory problems and bone loss around dental implants, so-called peri-implantitis. 5-8 A wide range of estimates of peri-implantitis prevalence has been reported in different studies, that is 6.2%-28% at the implant level. 9-15 Peri-implantitis is a multifactorial disease, and ongoing research is trying to identify the cause Summary Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or controls without Ti exposure.Background: Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis (controls) tissue is unknown.Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analysed with inductively coupled plasma mass spectrometry for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analysed microscopically with light microscopy, transmission electron microscopy and scanning electron microscopy with element analysis to investigate the presence of particulate Ti.Results: All patients lost one or more implants despite undergoing peri-implant or treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than control samples with a mean ± SD of 98.7 ± 85.6 and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and control biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue. Conclusion:We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions. K E Y W O R D Senergy dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, light microscopy, peri-implantitis, scanning electron microscopy, titaniumCheng Choo Lee at Umeå Core Facility Electron Microscopy, Umeå University, Sweden, for their help with the transmission and SEM.

In the present study, amount of titanium (Ti) released into the surrounding bone during placement of implants with different surface structure was investigated. Quantification of Ti released during insertion from three different implants was performed in this ex vivo study. Jaw bone from pigs was used as model for installation of the implants and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) was used for analysis of the released Ti. Implant surface were examined with scanning electron microscopy (SEM), before and after the placement into the bone. Ti was abraded to the surrounding bone upon insertion of a dental implant and the surface roughness of the implant increased the amount of Ti found. Diameter and total area of the implant were of less importance for the Ti released to the bone. No visible damages to the implant surfaces could be identified in SEM after placement.

Objective: To systematize evidence on the efficacy of botulinum toxin type A (BTA) in the treatment of bruxism measured through bite force or electromyography (EMG) at the masseter muscle.Method: Identification of relevant articles through databases PubMed, Web of Science, SCOPUS, Ovid and EBSCO and manual search were performed for sources from review articles. Studies scoring less than 3 on the Jadad Scale were excluded.Results: Four articles were included after an exclusion of 333 articles. 3 articles measured EMG and 1 bite force. 1 article did not record a significant drop of activity, 1 article recorded reduction midway and at final endpoint. 2 articles recorded initial reduction, but a non significant difference at later follow up. Conclusion: The available research is inconclusive and does not show enough evidence that bruxism can be treated with BTA injections. However, promising results have been shown in individual studies and further research in this area is needed. K E Y W O R D S bite force, botulinum toxins, bruxism, electromyography, review, tooth wear How to cite this article: Ågren M, Sahin C, Pettersson M. The effect of botulinum toxin injections on bruxism: A systematic review. J Oral Rehabil. 2020;47:395-402. https ://doi.

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.

Background and Aim Methods and Materials

The aim of the present study was to investigate whether titanium (Ti)-induced release of interleukin (IL)-1β acts through the assembly of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome. In addition, we examined whether particulate Ti or TiO2 activates the same intracellular pathways with the assembly of the NLRP3 inflammasome as Ti ions. Ti ions are known to induce IL-1β maturation and release by the formation of metal–protein aggregates. Wild-type THP-1 (wt.) cells and NLRP3− and ASC− (apoptosis-associated speck-like protein containing caspase recruitment domain (CARD)) knockdown cells were used in the experimental analyses. Macro- and nanoparticles (NPs) of both Ti and TiO2 were used as test agents. IL-1β release as a biomarker for inflammasome activation and cell viability was also analyzed. Periodate-oxidized adenosine triphosphate (oATP) was used to attenuate downstream signaling in NLRP3 inflammasome activation. Cellular uptake of Ti was examined using transmission electron microscopy. Cells exposed to the Ti-ion solution showed a dose-dependent increase in the release of IL-1β; conversely, exposure to particulate Ti did not result in increased IL-1β release. Cell viability was not affected by particulate Ti. Knockdown cells exposed to Ti showed a statistically significant reduction in the release of IL-1β compared with wt. cells (p < 0.001). Cellular uptake was detected in all Ti mixtures, and aggregates with various structures were observed. Ti ion–induced release of bioactive IL-1β in THP-1 cells involves the assembly of the NLRP3 inflammasome.

The cover image, by Mattias Pettersson et al., is based on the Original Article Titanium release in peri‐implantitis DOI: .