The role of metallic nano- and microparticles in the development of inflammation has not yet been investigated. Soft tissue biopsy specimens of the bone bed taken during surgical revisions, as well as supernatants obtained from the surface of the orthopedic structures and dental implants (control), were examined. Investigations were performed using X-ray microtomography, X-ray fluorescence analysis, and scanning electron microscopy. Histological studies of the bone bed tissues were performed. Nanoscale and microscale metallic particles were identified as participants in the inflammatory process in tissues. Supernatants containing nanoscale particles were obtained from the surfaces of 20 units of new dental implants. Early and late apoptosis and necrosis of immunocompetent cells after co-culture and induction by lipopolysaccharide and human venous blood serum were studied in an experiment with staging on the THP-1 (human monocytic) cell line using visualizing cytometry. As a result, it was found that nano- and microparticles emitted from the surface of the oxide layer of medical devices impregnated soft tissue biopsy specimens. By using different methods to analyze the cell–molecule interactions of nano- and microparticles both from a clinical perspective and an experimental research perspective, the possibility of forming a chronic immunopathological endogenous inflammatory process with an autoimmune component in the tissues was revealed.
The purpose of this study was to provide an immuno-mediated substantiation of the etiopathogenesis of mucositis and peri-implantitis based on the results of experimental, laboratory and clinical studies. The biopsy material was studied to identify impregnated nanoscale and microscale particles in the structure of pathological tissues by using X-ray microtomography and X-ray fluorescence analyses. Electron microscopy with energy-dispersive analysis identified the composition of supernatants containing nanoscale metal particles obtained from the surfaces of dental implants. The parameters of the nanoscale particles were determined by dynamic light scattering. Flow cytometry was used to study the effect of nanoscale particles on the ability to induce the activation and apoptosis of immunocompetent cells depending on the particles’ concentrations during cultivation with the monocytic cell line THP-1 with the addition of inductors. An analysis of the laboratory results suggested the presence of dose-dependent activation, as well as early and late apoptosis of the immunocompetent cells. Activation and early and late apoptosis of a monocytic cell line when THP-1 was co-cultured with nanoscale metal particles in supernatants were shown for the first time. When human venous blood plasma was added, both activation and early and late apoptosis had a dose-dependent effect and differed from those of the control groups.
The emission of nanoscale particles from the surfaces of dental implants leads to the cumulative effect of particle complexes in the bone bed and surrounding soft tissues. Aspects of particle migration with the possibility of their involvement in the development of pathological processes of systemic nature remain unexplored. The aim of this work was to study protein production during the interaction of immunocompetent cells with nanoscale metal particles obtained from the surfaces of dental implants in the supernatants. The ability to migrate nanoscale metal particles with possible involvement in the formation of pathological structures, in particular in the formation of gallstones, was also investigated. The following methods were used: microbiological studies, X-ray microtomography, X-ray fluorescence analysis, flow cytometry, electron microscopy, dynamic light scattering, and multiplex immunofluorescence analysis. For the first time, titanium nanoparticles in gallstones were identified by X-ray fluorescence analysis and electron microscopy with elemental mapping. The multiplex analysis method revealed that the physiological response of the immune system cells, in particular neutrophils, to nanosized metal particles significantly reduced TNF-a production both through direct interaction and through double lipopolysaccharide-induced signaling. For the first time, a significant decrease in TNF-a production was demonstrated when supernatants containing nanoscale metal particles were co-cultured with proinflammatory peritoneal exudate obtained from the peritoneum of the C57Bl/6J inbred mice line for one day.
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