Objective:The objective of this study was to perform a systematic review on the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues. Materials and Methods:A systematic review was carried out on the PUBMED electronic platform using the following keywords: Ti "OR" titanium "AND" dental implants "AND" nanoparticles "OR" nano-scale debris "OR" nanometric debris "AND" osteoblasts "OR "Cytotoxicity" OR "mutagenic" Results: Titanium nanoparticles in submicron-and nano-scale altered the behavior of cells in culture medium. An inflammatory response was triggered by macrophages, fibroblasts, osteoblasts, mesenchymal cells, and odontoblasts as indicated by the detection of several inflammatory mediators: IL-6, IL-1β, TNF-α and PGE2. The formation of a rich bioactive complex composed of calcium and phosphorus on titanium nanoparticles allowed the binding to proteins leading the cell internalization phenomenon. The nano-particles induced mutagenic and carcinogenic effects into the cells. Conclusions:The cytotoxic effect of debris released from dental implants depends on the size, concentrations, and chemical composition of the particles. A high concentration of particles on nanometric scale intensifies the inflammatory responses with mutagenic potential of the surrounding cells.Clinical relevance: Titanium (Ti) ions and debris have been detected in peri-implant tissues with different sizes and forms. The presence of metallic debris at peri-implant tissues also stimulates the migration of immune cells and inflamatory reactions. Cp Ti and TiO 2 micro-and nano-scale particles can reach the blood stream, accumulating in lungs, liver, spleen, and bone marrow.
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