Due to corrosion, a titanium implant surface can be a potential source for the release of micro (MPs) and nano-sized particles (NPs) into the biological environment. This work sought to evaluate the biokinetics of different sized titanium dioxide particles (TiO2 ) and their potential to cause cell damage. Wistar rats were intraperitoneally injected with 150 nm, 10 nm, or 5nm TiO2 particles. The presence of TiO2 particles was evaluated in histologic sections of the liver, lung, and kidney and in blood cells at 3 and 12 months. Ultrastructural analysis of liver and lung tissue was performed by TEM, deposit concentration in tissues was determined spectroscopically, and oxidative metabolism was assessed by determining oxidative membrane damage, generation of superoxide anion (O2(-)), and enzymatic and non-enzymatic antioxidants. TiO2 particles were observed inside mononuclear blood cells and in organ parenchyma at 3 and 12 months. TiO2 deposits were consistently larger in liver than in lung tissue. Alveolar macrophage O2(-) generation and average particle size correlated negatively (p < 0.05). NPs were more reactive and biopersistent in lung tissue than MPs. Antioxidant activity, particularly in the case of 5 nm particles, failed to compensate for membrane damage in liver cells; the damage was consistent with histological evidence of necrosis.

Although Ultrananocrystalline diamond (UNCD) has been proposed as a coating material for titanium biomedical implants, the biological effects and toxicity of UNCD particles that could eventually detach have not been studied to date. The biokinetics and biological effects of UNCD compared to titanium dioxide (TiO ) nanoparticles was evaluated in vivo using Wistar rats (n = 30) i.p. injected with TiO , UNCD or saline solution. After 6 months, blood, lung, liver, and kidney samples were histologically analyzed. Oxidative damage by membrane lipidperoxidation (thiobarbituric acid reactive substances-TBARS), generation of reactive oxygen species (superoxide anion- O2-), and antioxidant enzymes (superoxide dismutase-SOD, catalase-CAT) was evaluated in lung and liver. Histologic observation showed agglomerates of TiO or UNCD in the parenchyma of the studied organs, though there were fewer UNCD than TiO deposits. In addition, TiO caused areas compatibles with foci of necrosis in the liver and renal hyaline cylinders. Regarding UNCD, no membrane damage (TBARS) or mobilization of enzymatic antioxidants was observed either in lung or liver samples. No variations in O2- generation were observed in lung (Co: 35.1 ± 4.02 vs. UNCD: 48 ± 9.1, p > 0.05). Conversely, TiO exposure caused production of O2- in alveolar macrophages and consumption of catalase (p < 0.05). The studied parameters suggest that UNCD caused neither biochemical nor histological alterations, and therefore may prove useful as a surface coating for biomedical implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2408-2415, 2017.

As a result of corrosion, microparticles (MP) and/or nanoparticles (NP) can be released from the metallic implants surface into the bioenvironment. The biological response to these particles depends not only on the physico-chemical properties of the particles but also on host factors, such as age. Macrophages have attracted wide concern in biomedicine. The aim of this investigation was to study the age related biological response of macrophages to TiO2 -MP and NP in vitro. Alveolar macrophages (AM) obtained from young and senescent rats were cultured and exposed to TiO2 -MP and NP. Cell metabolism, superoxide anion (O2 (-) ) and nitric oxide (NO) generation, and cytokine release (IL-6, TNFα, IL-10) were measured. Cell metabolism was not affected by particle exposure. O2 (-) and NO generation increased in a dose dependent manner. A marked increase on IL-6 release was found in the young-AM subpopulation exposed to TiO2 -MP. Conversely, both particle sizes induced a dose dependent release of TNFα in senescent-AM. Only the highest concentration of TiO2 -particles caused a significant increase in IL-10 release in AM-cultures. These observations lend strong support to the suggestion that cellular response of macrophages to TiO2 -particles is age dependent. The biological effect of the particles would seem to be more deleterious in the senescent age-group.