Osteoblast adhesion on biomaterials.

Human tissue is structured mainly of self-assembled polymers (proteins) and ceramics (bone minerals), with metals present as trace elements with molecular scale functions. However, metals and their alloys have played a predominant role as structural biomaterials in reconstructive surgery, especially orthopedics, with more recent uses in non-osseous tissues, such as blood vessels. With the successful routine use of a large variety of metal implants clinically, issues associated with long-term maintenance of implant integrity have also emerged. This review focuses on metallic implant biomaterials, identifying and discussing critical issues in their clinical applications, including the systemic toxicity of released metal ions due to corrosion, fatigue failure of structural components due to repeated loading, and wearing of joint replacements due to movement. This is followed by detailed reviews on specific metallic biomaterials made from stainless steels, alloys of cobalt, titanium and magnesium, as well as shape memory alloys of nickel–titanium, silver, tantalum and zirconium. For each, the properties that affect biocompatibility and mechanical integrity (especially corrosion fatigue) are discussed in detail. Finally, the most critical challenges for metallic implant biomaterials are summarized, with emphasis on the most promising approaches and strategies.

Metallic implant biomaterials

Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions.

Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0−30 ppm nanoparticles (μg g-1) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos. Solubility was found to strongly influence the cytotoxic response. The results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated iron oxide and partial detoxification or recovery after treatment with zirconia, ceria, or titania. While in vitro experiments may never replace in vivo studies, the relatively simple cytotoxic tests provide a readily available pre-screening method.

In Vitro Cytotoxicity of Oxide Nanoparticles: Comparison to Asbestos, Silica, and the Effect of Particle Solubility†

Microplastics have become emerging contaminants, causing widespread concern about their potential toxic effects. In this study, the uptake and tissue accumulation of polystyrene microplastics (PS-MPs) in zebrafish were detected, and the toxic effects in liver were investigated. The results showed that after 7 days of exposure, 5 μm diameter MPs accumulated in fish gills, liver, and gut, while 20 μm diameter MPs accumulated only in fish gills and gut. Histopathological analysis showed that both 5 μm and 70 nm PS-MPs caused inflammation and lipid accumulation in fish liver. PS-MPs also induced significantly increased activities of superoxide dismutase and catalase, indicating that oxidative stress was induced after treatment with MPs. In addition, metabolomic analysis suggested that exposure to MPs induced alterations of metabolic profiles in fish liver and disturbed the lipid and energy metabolism. These findings provide new insights into the toxic effects of MPs on fish.

Uptake and Accumulation of Polystyrene Microplastics in Zebrafish (Danio rerio) and Toxic Effects in Liver.

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.

Effect of inorganic salts, amino acids and proteins on the degradation of pure magnesium in vitro

Characteristics and cytocompatibility of biodegradable polymer film on magnesium by spin coating.

When artificial hip or knee joints are implanted in the human body, they release metallic, ceramic, and polymeric debris into the surrounding tissues. The toxicity of the released particles is of two types: chemical, caused by the released soluble ions and monomers, and mechanical, a result of mechanical stimulation produced by the insoluble particles. In this study, the cytotoxicity of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and macrophages were examined to evaluate just their mechanical toxicity because these particles are not expected to release soluble metal ions. Different sizes and shapes of TiO2 particles were used to evaluate the effect of size and shape on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic particles does not depend on their chemical species. Cytotoxicity levels were lower than those of corresponding metal ions, indicating that the mechanical toxicity of particles is lower than the chemical toxicity of released soluble ions and monomers. The differences in size did not affect the mechanical toxicity of these particles. The dendritic particles had a higher cytotoxicity level for macrophages than did spindle and spheric particles.

Cytotoxicity evaluation of ceramic particles of different sizes and shapes

The release of metal ions due to active oxygen species generated by macrophages (Mphi) phagocytosing high-density polyethylene (HDPE) particles was studied in vitro to investigate the mechanism behind the release of metal ions from titanium implants into nearby tissues in the absence of wear and fretting in vivo. To determine the effects of Mphis on metal ion release, titanium disks were immersed in different solutions and the titanium ions released from the titanium disks into each solution were quantified. The results revealed that active oxygen species generated by Mphis induced the metal ion release. In particular, the ion release was accelerated with HDPE because the Mphis that phagocytosed HDPE generated more active oxygen species than Mphis that did not phagocytose any HDPE. Metal ions were also released by organic species in the absence of Mphis. These are some of the causes for metal ion release from titanium implants in the absence of wear and fretting in vivo.

Akiko Yamamoto

Papers

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

Effect of inorganic salts, amino acids and proteins on the degradation of pure magnesium in vitro

Characteristics and cytocompatibility of biodegradable polymer film on magnesium by spin coating.

Cytotoxicity evaluation of ceramic particles of different sizes and shapes

Metal ion release from titanium with active oxygen species generated by rat macrophages in vitro.