Cytotoxic effects of submicron- and nano-scale titanium debris released from dental implants: an integrative review



This integrative review aimed to report 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 search was carried out on the PubMed electronic platform using the following key terms: Ti “OR” titanium “AND” dental implants “AND” nanoparticles “OR” nano-scale debris “OR” nanometric debris “AND” osteoblasts “OR “cytotoxicity” OR “macrophage” OR “mutagenic” OR “peri-implantitis”. The inclusion criteria involved articles published in the English language, until December 26, 2020, reporting the effect of nano-scale titanium particles as released from dental implants on the toxicity and damage of osteoblasts.


Of 258 articles identified, 14 articles were selected for this integrative review. Submicron and nano-scale cp Ti particles 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 such as IL-6, IL-1β, TNF-α, and PGE2. The formation of a bioactive complex composed of calcium and phosphorus on titanium nanoparticles allowed their binding to proteins leading to the cell internalization phenomenon. The nanoparticles induced mutagenic and carcinogenic effects into the cells.


The cytotoxic effect of debris released from dental implants depends on the size, concentration, 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 ions and debris have been detected in peri-implant tissues with different size, concentration, and forms. The presence of metallic debris at peri-implant tissues also stimulates the migration of immune cells and inflammatory reactions. Cp Ti and TiO2 micro- and nano-scale particles can reach the bloodstream, accumulating in lungs, liver, spleen, and bone marrow.

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The authors acknowledge the support provided by the following FCT-Portugal projects: UID/EEA/04436/2013, NORTE-01-0145-FEDER-000018—HAMaBICo, and POCI-01-0145-FEDER-031035. The authors thank the financial support by the project IMPLDEBRIS-PL-3RL-IINFACTS-2019 at CESPU.

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Messous, R., Henriques, B., Bousbaa, H. et al. Cytotoxic effects of submicron- and nano-scale titanium debris released from dental implants: an integrative review. Clin Oral Invest (2021).

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  • Cytotoxicity
  • Titanium
  • Debris
  • Nanoparticles
  • Genotoxicity
  • Integrative review