**1. Introduction**

The current trend in total hip arthroplasty (THA) is to gradually prefer ceramic-based implants over metallic implants due to their excellent biocompatibility [1], both in bulk and particulate form, and high long-term survival [2]. Nowadays, the ceramic of choice for THA is zirconia-toughened alumina (ZTA), often in the form of the BIOLOX®*delta* material, the most commercially successful material. BIOLOX®*delta* (Delta) was developed in the early 2000s by CeramTec GmbH and is composed of 17 vol.% yttria-stabilized tetragonal zirconia particles (Y-TZP) embedded into an alumina matrix. The function of Y-TZP is to improve the toughness of the prosthetic material, through a mechanism called phase transformation toughening: under stress, a fraction of the tetragonal zirconia grains may undergo a phase transition to a monoclinic phase (t–m transformation). This phase has

**Citation:** Porporati, A.A.; Gremillard, L.; Chevalier, J.; Pitto, R.; Deluca, M. Is Surface Metastability of Today's Ceramic Bearings a Clinical Issue? *J. Compos. Sci.* **2021**, *5*, 273. https://doi.org/10.3390/jcs5100273

Academic Editor: Francesco Tornabene

Received: 1 August 2021 Accepted: 8 October 2021 Published: 14 October 2021

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a larger volume and thus sets the surrounding material under compressive stress. This increases the crack propagation resistance of the material. The alumina phase, on the other hand, provides hardness and wear resistance [3]. Furthermore, Delta also contains 0.3 w.% chromia, which imparts the pink color to the material, and about 3 vol.% of strontium hexaaluminate platelets, which further increases the fracture toughness of the ceramic composite. The stability of alumina matrix material bearings in the body of patients is still being discussed, despite the best long-term clinical outcomes shown by the arthroplasty registries when compared to alternative bearings [4–8]. Before being introduced into the medical market, the Delta material was thoroughly tested according to the available ASTM F2345-03 standard for in vitro testing, which states that a one-hour exposure at 134 ◦C under 2 bars water steam (in autoclave) corresponds to two years in vivo [9]. Extrapolations based on those tests predicted a very slow transformation (less than 5% increase over the first 10 years) [10]. However, investigations on revised Delta implants after few years (in some cases, months) in vivo [3,11–14], where the causes of revision were unrelated to the ceramic material, revealed worn areas [12,14,15], the presence of metal transfer [11–14], and a much higher monoclinic content than expected according to in vitro simulations [11,13]. This monoclinic content was always necessarily reported as the difference between worn and non-worn areas [11,15] because the initial monoclinic phase amount cannot be measured prior to implantation, and this value may vary slightly due to the manufacturer's batch processing [11].

Many material research groups have attempted to clarify this discrepancy between in vitro and in vivo results, but up to now, no consensus on the real causes has been found. Pezzotti et al. proposed one hypothesis [11,16–18] that ascribes this discrepancy to the effects of metal transfer. In fact, in correspondence with metal transfer, high wear values and high monoclinic contents in zirconia were measured [11–13]. According to Pezzotti et al. [11], in the aqueous body fluid environment, the autocatalytic dissociation of water molecules is promoted at the transferred metal's surface; this apparently causes an annihilation of oxygen vacancies first in the alumina phase and then in the tetragonal zirconia phase of Delta ceramics. This latter oxygen vacancy reduction should then trigger the tetragonal-to-monoclinic transformation in zirconia. This conclusion was supported by cathodoluminescence and X-ray photoelectron spectroscopies [11,16], and similar mechanisms were also observed in yttria-stabilized zirconia [19]. Although this explanation may sound plausible, especially in the case of metal transfer, it is not clear whether the initial data from the retrievals are consistent: the measured high wear could be due to the surface asperities produced by metal smearing, and not the ceramic. In addition, more likely, the presence of metal affects the quantification of the monoclinic phase by Raman spectroscopy because of the influence of metal on the intensity of Raman peaks due to plasmonic effects [20]. A poor signal-to-noise ratio could also affect spectra collected in the presence of chemisorbed proteins [21], which highlights the need for a thorough surface cleanup before Raman analysis.

Another explanation has been proposed by Perrichon et al. [15,22,23], who ascribe the discrepancy to the effect of shocks due to microseparation, which are not implemented in the ASTM in vitro standard, or in hip walking simulators. Perrichon et al. were able to demonstrate that using a specific in vitro test route that includes hip walking simulations, shock tests, and environmental aging tests, the discrepancy with in vivo studies can be reduced [23]. In this case, the monoclinic content on worn areas was much higher than on non-worn zones, in agreement with observations on retrieved implants. This shows that the phase transformation toughening mechanism was activated under stresses to limit mechanical damage. In other words, t–m transformation due to shock is not related to degradation due to aging.

The last explanation is related to the model used to relate the simulated aging kinetics obtained in the autoclave to in vivo aging. It is postulated that aging follows an Arrhenius law, and thus knowledge of its activation energy enables establishing a time–temperature equivalence. However, two main limits exist for this model: First, data at a low temperature take a long time to obtain and thus are hardly available; thus, it is not completely certain that the Arrhenian behavior is still valid around body temperature. Second, small uncertainties in the activation energy may lead to large variability in the time–temperature equivalence, while the ASTM standard tacitly considers a single activation energy for all zirconia-containing materials.

However, more importantly, it has been recently shown that the in vivo zirconia transformation in Delta does not affect the mechanical performance of the total hip arthroplasty components [24]. It follows that differences in the t–m transformation of zirconia in the Delta material between in vitro tests and ex vivo components may not be clinically relevant; therefore, solving the problem is conducted only for the sake of knowledge. In the following, we will try to explain the differences due to the measurement method.

Although it is clear that in vitro testing standards should be reviewed in order to better approach the conditions encountered by the implant inside the patient's body, one aspect may be overlooked: comparisons between in vitro and in vivo studies are based mainly on the value of Vm, the volume fraction of monoclinic zirconia, which is measured by Raman spectroscopy. However, currently, there is neither a standard that exists regarding how Vm should be measured from Raman spectra, nor sufficient explanations reported in the previous literature about how data collection and treatment have been performed. Very likely, each research group uses a different procedure for Vm quantification, which (at least) makes the comparison of Vm results obtained by different groups questionable. In addition, some data analysis procedures might lead to severe artefacts, with the consequence that wrong values of Vm are calculated, leading to flawed interpretations.

In this work, we show that the use of the Clarke/Adar equation—deemed unreliable by some research groups—is indeed the best choice for our measurement setup for Delta ceramics. This is confirmed by a control procedure using X-ray diffraction (XRD). Furthermore, we demonstrate—by analyzing a retrieval affected by metal transfer—that the effect of metal on the monoclinic transformation is negligible. Lastly, we show that specific choices in data analysis, such as the use of the absolute/integrated intensity, the choice of a baseline, or the overall signal-to-noise ratio of the spectrum, have a large impact on the obtainable results in terms of Vm. These results clearly suggest that a standard for Vm quantification using Raman spectroscopy (including sample preparation, spectroscopic procedures, and data treatment) should be promptly put in place.
