Background

The biological reaction to some zirconia ceramics, mainly tetragonal zirconia polycrystals (3Y-TZP), has been reported in the literature. Various forms have been used including bulk materials, particulates, fibres and coatings. The in vivo studies are summarised below.
Biocompatibility in Soft Tissue

There have been several studies into the behaviour of zirconia ceramics implanted into soft tissues. These are summarised in the following sections.
Tetragonal Zirconia Polycrystal

When implanted in the paraspinalis muscles of rats for periods up to 12 weeks tetragonal zirconia polycrystals tended to become encapsulated with fibrous tissue. Tis behaviour was not significantly different from that observed for alumina control samples.

Similarly, tetragonal zirconia polycrystals elicited a similar response to alumina controls when implanted subcutaneously into rats for periods up to 12 months. Both materials became encapsulated by a ~50 mm thick layer of fibrous tissue which was independent of implantation time. I all cases there was little evidence of any inflammatory response.
Partially Stabilise Zirconia

Magnesia partially stabilised zirconia (Mg-PSZ) was found to biocompatible when implanted percutaneously into sheep. It also became encapsulated by a thin layer of fibrous tissue. A similar result was obtained for Mg-PSZ samples implanted into the paraspinalis muscles of rabbits for times up to 6 months. In no instance did the zirconia materials elicit any form of adverse tissue reaction or produce an inflammatory response.
Zirconia Coatings

Plasma sprayed coatings of unstabilised zirconia on 316L stainless steel implanted into the trachea of rabbits and into the trachea, vena cava, or vas deferens of dogs did not produce any adverse reaction. The tubes, however, tended to become occluded with fibrous tissue.
Zirconia Wear Particles

To simulate wear particles from an artificial hip joint, suspensions of various ceramic powders were injected into the peritoneal cavity of mice to simulate the wear debris that might be produced by an artificial hip joint. The type and number of cells present in the lavage retrieved from the peritoneal cavity after 24 hours was determined and it was found that 5-8 mm diameter zirconia particles were non-toxic and elicited cellular reactions similar to those of 1-13 mm diameter alumina particles.
Zirconia Fibres

When compared with alumina fibres, zirconia fibres injected intraperitoneally into rats, were encapsulated by a thinner fibrous membrane, were more readily eliminated by phagocytosis, and were deposited in higher concentrations in the lymph nodes. It is possible that these results reflect the slightly smaller diameter and length of the zirconia fibres.
Zirconia Dust

Zirconia dust inhaled by laboratory animals in dosages of 100 mg/m3 for one month and 15 mg/m3 for two months, and 5 mg/m3 for one year, did not have any significant physical or biochemical effects on the animals. Consequently, a maximum threshold limit of 5 mg Zr/m3 in air for exposure to zirconium compounds was established by an American regulatory health body.
Biocompatibility in Hard Tissue
Tetragonal Zirconia Polycrystal and Stabilised Zirconia

Tetragonal zirconia polycrystals were shown to be biocompatible when implanted into rabbit bone, although they exhibited bioinert behaviour. X-ray elemental microanalysis of the interfacial zone between tetragonal zirconia polycrystals and bone showed no evidence of dissolution of zirconium or yttrium cations into the surrounding tissue.

The biological response of bone to zirconia ceramics has been reported to be similar to the response generally observed for alumina. For example, a report on tetragonal zirconia polycrystals and alumina implanted into rat mandibles for periods up to 56 days showed similar thicknesses of fibrous tissue and bone contacting each ceramic. Similarly, quantitative optical microscopy analysis of the bone-ceramic interface of zirconia and alumina specimens implanted in canine femurs revealed that the interface between tissue and ceramic consisted of a mixture of both new bone and fibrous tissue in contact with the ceramic. From this it was concluded that the tissue response was almost identical for the two ceramics. A similar response has been reported for CaO-stabilised zirconia.
Zirconia Coatings

Plasma-sprayed coatings of unstabilised zirconia and alumina on a commercial dental alloy implanted in the mandibles of dogs were shown to elicit the same response. In both instances the coatings failed to achieve satisfactory osseointegration for fixation of the implant in bone. However, in an another study in which tetragonal zirconia polycrystals and alumina samples were implanted in the tibial medullary cavity of rabbits, there was no adverse tissue response to either of the ceramics although there was significantly less new bone formed around tetragonal zirconia polycrystals than around alumina.