| The biocompatibility, or reaction of some zirconia ceramics, in particular 3mol% yttria stabilised tetragonal zirconia polycrystal (3Y-TZP) to physiological environments or simulated physiological environments have been documented in the literature. Studies have been performed on both particulate and bulk forms using cell culture assays (in vitro techniques) and by implantation into soft tissue and bone (in vivo techniques). Findings from these studies are reviewed below. Cytoxicity The biocompatibility of zirconia has been evaluated in a limited number of in vitro assays. Cytotoxicity assays using animal cells such as mouse fibroblasts and Chinese hamster fibroblasts have been performed by seeding them onto dense Y- tetragonal zirconia polycrystal substrata. In both instances, cells remained morphologically normal and showed normal proliferation rates on the ceramic suggesting it was not cytotoxic. In Vitro Biocompatibility of Zirconia Ceramics Compared to Other Biocompatible Ceramics In an investigation into the behaviour of mouse fibroblasts on various dense ceramics, it was found that the adhesive strength and growth rate of cells on zirconia was comparable with those on other materials accepted as being biocompatible, including hydroxyapatite, tricalcium phosphate, and tissue culture plastic. The type of zirconia ceramic involved with this study, although not specified, was produced by a Japanese and was likely to be yttria stabilised tetragonal zirconia polycrystal. While not specifically stated, the results of this study implied that since cells attached and proliferated on the zirconia substrate, and the ceramic was not cytotoxic. These findings were similar to those of another study in which it as found that the growth rates of mouse fibroblasts on zirconia substrata were similar to those on hydroxyapatite. Cytotoxicity of Zirconia Wear Debris Using mouse fibroblasts, the cytotoxicity of zirconia wear particles was evaluated using zirconia particles approximately 0.02 mm in size produced by a pin-on-disk wear machine. While the wear debris significantly decreased the growth rate of cells, the growth rate was not significantly different from that of alumina and hydroxyapatite wear debris. Cytotoxicity of Zirconia Fibres The cytotoxicity of commercially available zirconia fibres (2-5 mm diameter, 5-200 mm long) was compared to that of alumina fibres (2-6 mm diameter, 6-100 mm long). Using assays involving rat peritoneal macrophages and a quantitative cell counting method, it was found that after two hours in culture, the responses of the macrophages to the zirconia and alumina were almost identical and consisted of less than 5% cell death with approximately 50% of all cells containing phagocytosed fibres. As Both ceramics are relatively chemically inert, the similarity in their cytotoxicities was possibly due to similarities in the morphology of the fibres. It was also noted that both ceramics were non-fibrogenic, which again reflects the benign nature of the morphologies of the fibres. Haemolytic Activity of Zirconia Ceramics Using a standard haemolysis test, it was found that, a 3.0 mol% Y2O3-ZrO2 powder having a surface area of 42.6 m2/g did not elicit any haemolytic effect. Consequently, it was considered that the corresponding bulk ceramic or coating could be used in blood-contacting devices. Summary The evaluation of biocompatibility using in vitro assays has not been reported in the literature for any other zirconia ceramics such as ceria stabilised tetragonal zirconia polycrystal (Ce-TZP), and magnesia partially stabilised zirconia (Mg-PSZ). It may be expected that since the materials are chemically inert, they would not be cytotoxic. However, this remains to be confirmed. | 
