The objective of this study was to evaluate the effects of metal ions, which may be released from orthopedic or dental implants, on osteoblast metabolism and differentiation. ROS 17/2.8 cells were cultured in F-12 medium for 7 days. Then Al+3, Co+2, Cr+3, Ni+2, Ti+4, and V+3 were added at concentrations less than their cytotoxic concentrations. After 3 days, DNA synthesis, succinate dehydrogenase activity, alkaline phosphatase (ALP) activity, and culture calcification were assessed. Northern blots were performed for ALP, osteocalcin (OCN), and osteopontin (OPN) mRNA transcription. The data indicated that Cr+3 and A1+3 had few inhibitory effects on ROS cell metabolism below their cytotoxic concentrations, Ni+2, Co+2, Ti+4, and V+3 affected all these parameters of ROS cell metabolism at concentrations below cytotoxic levels. For RNA analysis, A1+3 significantly suppressed the expression of ALP, OCN, and OPN at both cytotoxic and noncytoxic concentrations. Co+2 specifically suppressed ALP expression at cytotoxic concentrations. Cr+3 and Ni+2 inhibited OCN, OPN, and ALP gene expression only at cytotoxic concentrations. For Ti+4 and V+3 ions, gene expression at cytotoxic levels was not significantly affected as compared with the effects at noncytotoxic level. These results show that metal ions may alter osteoblast behavior even at subtoxic concentrations, but do not always affect the expression of all genes similarly.

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Effects of metal ions on osteoblast-like cell metabolism and differentiation

It is commonly accepted that titanium and the titanium alloying elements of tantalum, niobium, zirconium, molybdenum, tin, and silicon are biocompatible. However, our research in the development of new titanium alloys for biomedical applications indicated that some titanium alloys containing molybdenum, niobium, and silicon produced by powder metallurgy show a certain degree of cytotoxicity. We hypothesized that the cytotoxicity is linked to the ion release from the metals. To prove this hypothesis, we assessed the cytotoxicity of titanium and titanium alloying elements in both forms of powder and bulk, using osteoblast-like SaOS(2) cells. Results indicated that the metal powders of titanium, niobium, molybdenum, and silicon are cytotoxic, and the bulk metals of silicon and molybdenum also showed cytotoxicity. Meanwhile, we established that the safe ion concentrations (below which the ion concentration is non-toxic) are 8.5, 15.5, 172.0, and 37,000.0 microg/L for molybdenum, titanium, niobium, and silicon, respectively.

Cytotoxicity of Titanium and Titanium Alloying Elements

Microstructures, mechanical properties and cytotoxicity of low cost beta Ti-Mn alloys for biomedical applications.

In this study the toxic effects of chromium, nickel, and cobalt extracts on in vitro cultured lymphocytes were evaluated. Graphite furnace atomic absorption spectrometry was used to measure the ion concentration. After serial dilution of the extracts, the viability of lymphocytes at 24,48, and 72 h was estimated by flow cytometry, including propidium iodide staining and light scatter property assessment, and by MTT reduction test. The results of the investigation allowed us to conclude that 1) standardization of the procedure for preparing extracts is fundamental to obtaining repeatability of results; 2) the toxicity of an extract cannot be evaluated with a single viability assay; a combination of functional and structural tests is required; 3) when methods based on enzymatic reactions are performed, e.g. MTT test, it is advisable to replace the extract containing metal ions with fresh medium in order to avoid any interference with viability testing; 4) the amount of Co and Ni in the extract is similar, but the Cr release is very poor; 5) the lower toxicity of Cr extract probably is due to the lower ion concentration; 6) the assessment of 50% cytotoxic concentration (TC50) allows quantification of materials toxicity and comparison of various metals; and 7) the determination of a noncytotoxic concentration, i.e., a concentration lower than TCIO, is required for subsequent investigation of cell functions because such studies can be carried out only on viable cell population. 0 1996 John Wiley & Sons, Inc.

Assessment of metal extract toxicity on human lymphocytes cultured in vitro.

Improvement of microstructure, mechanical and corrosion properties of biomedical Ti-Mn alloys by Mo addition

The cytotoxic effects of pure metals on L-929 mouse fibroblasts were examined using extracts obtained by dynamic extraction of Cu, Al, Ti, V, Cr, Mo, Mn, Fe, Co and Ni. The order of cytotoxicity expressed in ppm was Cr greater than V greater than Co greater than Fe greater than Mn greater than Cu greater than Ni much greater than Mo. On the other hand, the order in mM was Cr greater than Co greater than V greater than Fe greater than Mn greater than Cu greater than Ni much greater than Mo. Al and Ti showed no cytotoxicity. Thus, the cytotoxicity of pure metals was dependent on their concentration and the chemical state in the extracts.

S Takeda

Papers

Cytotoxicity of pure metals