http://lbmd.coe.pku.edu.cn/PDF/2009biomaterials01.pdf

In vitro corrosion and biocompatibility of binary magnesium alloys

Cellular responses induced by silver nanoparticles: In vitro studies

Metallic biomaterials are generally used for replacement of structural components of the human body such as bones, joints, and tooth roots. When they are implanted inside a body, metallic biomaterials may corrode and/or wear, releasing metal ions and debris which may have toxic effects on tissues and organs. Since it is important for biomaterials to have no toxicity against a living body, a systematic and quantitative evaluation of the cytotoxicity of metallic elements is required for the development of new metallic biomaterials with superior biocompatibility. In this study, the cytotoxicity of 43 metal salts were evaluated by the colony formation method using two kinds of cultured cells. The effects of the difference in valence numbers of metallic elements in the salts on cytotoxicity were examined. The cytotoxicity of the salts of metallic elements' oxo acids was also investigated. As a result, the intensity of metal salts' cytotoxicity tends to be quite similar between MC3T3-E1 and L929 (the correlation coefficient of metal salts' IC50s is 0.82). The intensity of metal salts' cytotoxicity depends on the kinds of metallic elements, their chemical states, and concentrations. The IC50 of the highest toxic salt is 1.36 x 10(-6) mol L-1, which differs four orders of magnitude from the IC50 of the lowest toxic salt. K2Cr2O7, CdCl2, VCl3, AgNO3, HgCl2, SbCl3, BeSO4, and InCl3 are high toxic salts in which IC50s are smaller then 10(-5) mol L-1 for both or either of the cell lines. HgCl, Tl(NO3)3, GaCl3, CuCl2, MnCl2, CoCl2, ZnCl2, NiCl2, SnCl2, IrCl4, TlNO3, CuCl, RhCl3, Pb(NO3)2, Cr(NO3)3 and Bi(NO3)3 are relatively high toxic salts in which IC50s are smaller than 10(-4) mol L-1 for both or either cell lines.

Cytotoxicity evaluation of 43 metal salts using murine fibroblasts and osteoblastic cells.

How smart do biomaterials need to be? A translational science and clinical point of view ☆

Biological interactions of dental cast alloys with oral tissues.

Recent data suggest that under certain conditions, various metal cations are released from dental alloys. These ions may produce adverse effects in various cell types in vivo. In this study, the cytopathogenic effects of 13 metal cations on murine L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells were analyzed in vitro. Several metal cations (dose range, from 0.0033 to 1.0 mmol/L) were found to induce dose-dependent inhibition of 3H-thymidine incorporation into cultured fibroblasts. The rank order of potency (lowest observed effect level, LOEL) for L-929 fibroblasts was: Ag+ > Pt4+ > Co2+ > In3+ > Ga3+ > Au3+ > Cu2+ > Ni2+ > Zn2+ > Pd2+ > Mo5+ > Sn2+ > Cr2+. A similar rank order of potency was obtained for primary human gingival fibroblasts: Pt4+ > Ag+ > Au3+ > In3+ > Ga3+ > Ni2+ > Co2+ > Zn2+ > Cu2+ > Cr2+ > Pd2+ > Mo5+ > Sn2+. In primary human mast cells, Ag+ and Au3+ caused dose-dependent toxic histamine release, whereas the other metal cations were ineffective over the dose range tested. To investigate the mechanism of metal cation-induced effects, we performed DNA as well as electron microscopic analyses on cultured fibroblasts. Both the DNA pattern and the ultrastructure of L-929 cells and gingival fibroblasts after exposure to cytopathogenic metal cations revealed signs of necrosis but no signs of apoptosis. Together, our data provide evidence that various metal cations produce dose-dependent cytopathogenic effects in distinct cell types, including human gingival fibroblasts and human tissue mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of L-929 Fibroblasts, Human Gingival Fibroblasts, and Human Tissue Mast Cells to Various Metal Cations

Recent data suggest that distinct metal ions can be released from dental alloys or other biomaterials, and may cause toxic effects on various cells. In this study, the effects of 14 metal ions on histamine release from human blood basophils (n = 4), isolated tissue mast cells (lung n = 8, uterus n = 2, skin n = 1, gingiva n = 1), the basophil cell line KU-812, and the mast cell line HMC-1 were analyzed. Of the 14 metal ions, Ag+ (0.33 mM) and Hg2+ (0.33 mM) were found to induce release of histamine in blood basophils, KU-812, mast cells, and HMC-1. The effects of Ag+ and Hg2+ were dose dependent and were observed within 60 min of incubation. In primary mast cells and basophils, AU3+ (0.33 mM) also induced histamine release, whereas no effects of Au3+ on HMC-1 or KU-812 cells were seen. The other metal ions showed no effects on primary or immortal cells within 60 min. However, Pt4+ (0.33 mM) induced histamine liberation in HMC-1 and lung mast cells after 12 h. The Ag+- and Hg2+-induced rapid release of histamine from HMC-1 was associated with ultrastructural signs of necrosis, but not apoptosis. In contrast, prolonged exposure to Pt4+ (0.33 mM, 14 h) induced apoptotic cell death in HMC-1 cells, as assessed by electron microscopy and DNA analysis. Together, certain metal ions induce distinct cytopathogenic effects in mast cells and basophils. Whereas Ag+, Hg2+, and Au3+ cause direct toxicity, Pt4 causes cell death through induction of apoptosis. Whether such effects contribute to local adverse reactions to metal-containing biomaterials in vivo remains to be determined.

A. Ellinger

Papers

Response of L-929 Fibroblasts, Human Gingival Fibroblasts, and Human Tissue Mast Cells to Various Metal Cations

Metal ion-induced toxic histamine release from human basophils and mast cells