State of the Art of Different Zirconia Materials and Their Indications According to Evidence-Based Clinical Performance: A Narrative Review

The aim of this study was to perform a narrative review to identify the modifications applied to the chemical structure of third- and fourth-generation zirconia ceramics and to determine the influence of these changes on the mechanical and optical properties. A bibliographical search using relevant keywords was conducted in the PubMed® and EBSCO databases. The abstracts and full texts of the resulting articles were reviewed for final inclusion. Fifty-four articles were included in this review. The analyzed topics were: (1) the composition of first- and second-generation zirconia materials (Y-TZP), (2) the behavior of the studied generations in relation to mechanical and optical properties, and (3) the modifications that were carried out on third-generation (5Y-TZP) and fourth-generation (4Y-TZP) zirconia materials. However, studies focusing on these specific characteristics in third- and fourth-generation zirconia materials are scarce. The review shows that there is a lack of sufficient knowledge about the chemical modifications of zirconia in the new generations.

Yttria-stabilized tetragonal zirconia polycrystalline is termed Y-TZP. Zirconia-based ceramics used for biomedical purposes typically exist as a metastable tetragonal partially stabilized zirconia (PSZ), which means that trapped energy still exists within the material, preventing the system from transforming into the monoclinic phase at room temperatures. However, 3 mol% yttria-stabilized tetragonal zirconia polycrystalline (3Y-TZP) suffers a phase transformation when mechanical or physical stress is applied. It has been observed that fatigue creates micro-cracks in the structure of zirconia materials. When a crack propagates in 3Y-TZP (that has these metastable tetragonal particles), a stress-induced transformation occurs at the end of the crack and only the particles near this transform from the tetragonal into the monoclinic phase; this process is called transformation toughening (TT) [6,10]. This transformation toughens the material in the following two different ways: the energy needed for fracture is first dissipated during transformation and second through residual compressive stress [4,7,11,21,25].
On the other hand, 3Y-TZP under oral conditions has shown an accelerated aging, affecting a long lasting prosthesis. Scientists who have investigated the biomaterial behavior have named this phenomenon as "low temperature degradation (LTD)", where the tetragonal zirconia (t-ZrO 2 ) phase spontaneously transforms to the monoclinic (m-ZrO 2 ) phase as a response to the variation of temperature in the mouth and the presence of humidity (hydrothermal aging), regardless of any mechanical stress. The consequences of hydrothermal aging are surface roughening due to loss of crystals, enhanced wear rates, detrimental strength, and fracture toughness, followed by catastrophic failures [4,8,11,12,16].
In 2015, a new ceramic system was introduced to the market: the third-generation 5-mol% yttria-stabilized tetragonal zirconia polycrystal (5Y-TZP). Increasing the yttria content (Y 3 O 2 ) to 5 mol% was a modification that offered enhancement in the translucency of zirconia. The result is a fully stabilized zirconia with a stable cubic-tetragonal microstructure. The cubic phase reaches approximately 50% of the structure. The size and number of the crystals, which are larger than the 3Y-TZP, favor the light transmission, reducing the refraction effect and giving better translucency. On the other hand, an increase in the number of cubic crystals affects the crack propagation pattern, reducing the flexural strength and the fracture toughness of the material [1,6,10,12,30].
It is relevant to recall the findings attained by Zhang et al. [13] in 2020 that describe 3Y-TZP ceramics. These ceramics allow less light transmission because of the large refraction of light in two different directions (optically anisotropic)-an effect of the tetragonal phase-causing light diffusion and light deflection at the grain boundaries that enhance the translucency of zirconia ceramics [12,17,[31][32][33][34].
The mechanism for increasing yttria oxide as a strategy to reach a higher translucency in the zirconia materials involves better aging stability but lower flexural strength and fracture toughness, mainly due to the change in the phase composition [35][36][37][38][39]. Compared with 3Y-TZP that consists of~80 wt% tetragonal phase and~20 wt% cubic phase, PSZ stabilized with 4-6 mol% yttria used for dental purposes contains a 40-70 wt% cubic phase influenced by the yttria stabilizer concentration and the sintering temperature. Increasing the cubic phase in the zirconia structure transforms the composition into a nonbirefringent (refraction in two directions) and non-transformable (loss of grains and aging) under humidity and stress conditions [13][14][15][17][18][19].
In 2017, manufacturing companies launched the fourth-generation 4-mol% yttriastabilized tetragonal zirconia polycrystals (4Y-TZP) of zirconia. Compared with the thirdgeneration, the yttria content was reduced to 4-mol%, which led to an enhancement of the flexural strength and fracture toughness, with a combined reduction in translucency [6,10,14,31]. Comparing the strength, toughness, and translucency of zirconia restorations allows clinicians and dental lab technicians to make assertive decisions based on the evidence of prosthetic restoration on one or more than three units. For this reason, the research question sought to identify the expectancy of an enhancement of the different properties when comparing the third-and fourth-generation of zirconia materials.
The aim of this study was to retrieve the papers that analyze the modifications performed in the chemical structure of third-and fourth-generation zirconia ceramics in order to determine how these structural changes have influenced the strength, toughness, and translucency of these materials.

Study Selection
This study consisted of an extensive search of the literature available on dental materials worldwide. The search was limited exclusively to papers in English, between 2015 and 2022, that feature on the two main search engines (PubMed ® and EBSCO) and that are published in of the most influential indexed journals in the materials and dental field. A first search was performed in October 2021 and a second search was conducted in July of 2022.

Inclusion Criteria
Clinical trials (randomized controlled trials), meta-analysis, systematic reviews, in vitro studies, and literature reviews were included in the present study. The following characteristics were taken into account: zirconia materials, translucent zirconia, cubic zirconia, ultra-translucent zirconia, mechanical properties, chemical structure, and load bearing of translucent zirconia.

Exclusion Criteria
Books and documents, all papers in a foreign language (not in the English language), and zirconia materials investigated in other applications different from fixed prosthodontics were excluded.

Study Quality Assessment
The search strategy was designed and set up by one reviewer (A.A.), who also performed the electronic search. All the studies that fulfilled the inclusion criteria were included in this review. The title and abstracts of all articles identified by the electronic search were read and assessed by one of the authors (A.A.). A shortlist of studies was then compiled and subjected to full text analysis and data extraction by the contributing authors. A manual search of the analyzed articles was also carried out. The methodological quality of all selected full-text articles was assessed using the guidelines given by PRISMA and CONSORT [40].
First, the authors analyzed those papers that described zirconium oxide as a pure element in nature and its modifications, including its chemical structure, phase transformation, and low-temperature degradation. Second, the authors classified those papers that reported data on third-and fourth-generation zirconia materials.

Results
The original search strategy-based on keywords mentioned-resulted in 322 papers. However, the total number of papers that met the inclusion criteria for the review was 64, whereby 45.6% addressed first-and second-generation zirconia materials and 54.3% studied third-and fourth-generation zirconia materials. A total of 64 articles was reviewed, of which 20 were discarded and 44 related to third-and fourth-generation zirconia were used, with a further 10 articles added to address generalities of the review. The flow chart of the obtained results of the literature search is given in Figure 1. This study aimed to understand the chemical composition of zirconia ceramics to determine which modifications have been carried out. The first selection of papers lowed the authors to categorize the composition of first-and second-generation zirco materials (Y-TZP) and to identify the behavior of the studied generations of zirconia terials regarding abrasiveness and wear, marginal accuracy, and cementation. The sec selection permitted to establish the modifications that were carried out in third-genera (5Y-TZP) and fourth-generation (4Y-TZP) zirconia materials, allowing to understand h these modifications have influenced the flexural strength, fracture toughness, and tra lucency of the available materials. Studies that addressed these specific characteristic third-and fourth-generation are scarce.
All selected papers are distributed according to the information they offer regard the composition and features of zirconia materials. A summary of the in vitro studies the observational study articles reviewed in this paper can be found in Table 1. This study aimed to understand the chemical composition of zirconia ceramics and to determine which modifications have been carried out. The first selection of papers allowed the authors to categorize the composition of first-and second-generation zirconia materials (Y-TZP) and to identify the behavior of the studied generations of zirconia materials regarding abrasiveness and wear, marginal accuracy, and cementation. The second selection permitted to establish the modifications that were carried out in third-generation (5Y-TZP) and fourth-generation (4Y-TZP) zirconia materials, allowing to understand how these modifications have influenced the flexural strength, fracture toughness, and translucency of the available materials. Studies that addressed these specific characteristics in third-and fourth-generation are scarce.
All selected papers are distributed according to the information they offer regarding the composition and features of zirconia materials. A summary of the in vitro studies and the observational study articles reviewed in this paper can be found in Table 1.

(in vitro)
Moqbel et al. [15] (Germany) Evaluate the influence of aging and surface treatment on surface roughness, biaxial flexural strength (BFS), and Vickers hardness (VHN) of translucent dental zirconia.
Eighty disc-shaped zirconia specimens. Size: 1.2 mm in thickness and 12 mm in diameter.
Half were not aged and the other half were aged in autoclave for 20 hrs.

4Y-TZP
Aging and particle air abrasion increased the BFS. The hardness was not influenced significantly by aging.
Particle air abrasion and aging demonstrated a significant transformation from tetragonal phase to-monoclinic phase, which led to significant increase of BFS.

(in vitro)
Na-Kyoung Yu et al. [41] (Korea) Evaluate the effect of two coloring liquids and the position of multi-layered zirconia on flexural strength.
Sixty multi-layered specimens were divided into incisal and cervical positions. Three subgroups (n = 10): non-shaded, acid-based coloring liquid, and aqueous coloring liquid.
There was no statistically significant difference among all groups.
The different coloring liquids did not affect the flexural strength of multi-layered zirconia of all positions

(in vitro)
Jansen et al. [9] (Germany) Higher sintering temperatures increased the grain size but did not change the crystal phase concentration.
Increasing the content of yttrium oxide in an attempt to improve the optical properties can reduce the mechanical properties after aging of the ceramic.

(in vitro)
Auzani et al. [31] (Brazil) Evaluate the effect of shading procedures on fatigue performance and optical properties on 4Y-TZP.
Seventy-five discs of Y-TZP ceramic were divided into 5 groups (n = 15

3Y-TZP 4Y-TZP 5Y-TZP
The three zirconia ceramics showed a similar and limited amount of wear. The wear resistance was higher than lithium-disilicate.
The threshold in stress intensity for crack growth along with microstructural homogeneity and surface degradation are also key parameters that should be taken into account.

4Y-TZP 5Y-TZP
DD cubeX2 had higher positive values on mechanical properties than Prettau Anterior both before and after artificial aging for 10 hrs.
Within the limitations of the present in vitro study, both DD cubeX2 and Prettau Anterior seem to be relatively aging resistant. However, a wider range of measured flexural strength indicated that Prettau Anterior probably is a less stable material than DD cubeX2, which also means that the flexural strength of DD cubeX2 could be more predictable.

(in vitro)
Hayasi et al. [22] (Japan) Clarify the influence of translucent tetragonal zirconia polycrystals on wear properties of esthetic dental materials.
Disc shaped. Size: 1.0 mm in thickness and 13 mm in diameter.

5Y-TZP
The wear volume of TZP was extremely small. Polished translucent TZP indicates that wear hardly occurs.
No visible wear was found on translucent TZP.

(in vitro)
Ebeid et al. [44] (Germany) Evaluate the effect of zirconia surface treatment on its surface roughness, phase transformation, and biaxial flexural strength (BFS) in pre-sintered and post-sintered stages.
Forty zirconia ceramic discs. Size: 1.2 mm in thickness and 12 mm in diameter.

5Y-TZP
The pre-sintered treated group and control group showed no monoclinic phase, while the post-sintered group showed higher portions of monoclinic phase. BFS was higher in post-sintered group.
Air abrasion in the pre-sintered stage might be a surface treatment method to produce better surface roughness without subjecting it to early degradation. The high amount of cubic phase in 5Y-TZP improves translucency but at the expense of strength and toughness.
Hydrothermal degradation takes place in the state-of-the-art 3Y-TZP and is minimal in the third-generation zirconia.
In the current generation of so-called tetragonal zirconia, short aging times have been observed. Glaze acts as a barrier against hydrothermal degradation.

(in vitro)
Yan et al. [39] (EEUU) Evaluate the load-bearing capacity of monolithic lithium disilicate and novel ultra-translucent zirconia restorative systems of various compositions.
Ten disc-shaped specimens were prepared from three dental zirconia and lithium disilicate (n = 10

3Y-TZP
Bond strength is affected by particle size factor; 110 µm particles promoted higher bond strength.
The 30 µm and 110 µm silica coating created t-m phase transformation.

(in vitro)
Schatz et al. [29] (Germany) Evaluate the influence of specimen preparation and test method on flexural strength of monolithic zirconia.
Total of 720 specimens.

3Y-TZP
The different polishing procedures influenced the mean flexural strength independently of which zirconia was tested and which test method was applied. After sintering the wet polished specimen produced significantly higher flexural strength than specimens polished before sintering.
The specimen preparation method significantly impacts the flexural strength; roughness was higher with dry polished specimens.

Discussion
Zirconia materials have evolved into several formulations, depending on powder composition, sintering additives, heat treatment, and other processing factors.
In general, a higher yttria content and sintering temperature will have a greater cubic content and better translucency. Nevertheless, this also triggers a lower strength and toughness [1,5,10,12]. The structure allowed (5Y-0.05Al) to have a much higher translucency than other (3Y-TZP) ceramic systems, which contained about 90% birefringent tetragonal zirconia. Cubic zirconia is optically isotropic, without light scattering at the grain boundaries [29,34,43,[47][48][49]. Moreover, since cubic zirconia is a stable phase and the yttria content in the residual tetragonal zirconia of (5Al-0.05Al) was high (about 3.9 mol%), 5Y-0.05Al was resistant to hydrothermal aging [16]. However, the mechanical properties of (5Y-0.05Al) are a crucial drawback. Cubic zirconia is brittle and the tetragonal zirconia with a higher yttria content has a lower ability of transformation toughening. Therefore, (5Y-0.05Al) had lower fracture toughness. The low toughness, combined with the larger grain size of (5Y0.05Al), also resulted in a much lower strength [5,10,12,15,17]. Third-generation zirconia (5Y-TZP) exhibits 35-40% translucency and 500 MPa BFS, which does not fulfill the mechanical requirements for multiple-unit fixed dental prosthesis [9,15]. Increasing the content of yttrium oxide in an attempt to improve the optical properties can reduce the strength and toughness after aging of the ceramic [9,15,17].
Zhang investigated the remaining tetragonal phase and its role in 4Y-and 5Y-PSZ (mol% yttria partially stabilized zirconia). Both materials had similar basic properties. However, 5Y-PSZ (mol% yttria partially stabilized zirconia) had a variation on the microstructure. When 5Y-PSZ was processed from an yttria co-precipitated powder, in which the 5 mol% Y 2 O 3 stabilizer was already homogeneously distributed inside, the zirconia starting powder had a significantly higher translucency, biaxial strength, and aging stability, demonstrating that the cubic content and the microstructure of the remaining tetragonal grains had considerable influence on the properties of 4Y-and 5Y-PSZ (mol% yttria partially stabilized zirconia) [13,[23][24][25][26][27].
The literature supports the findings regarding the difference in the properties between third-and fourth-generation zirconia materials. The third-generation shows better optical properties than the fourth-generation zirconia materials, but the fourth-generation zirconia exhibits better strength.
The abrasiveness and wear are closely related to grain size; thus, third-and fourthgeneration zirconia show a similar grade of wear that is very close to enamel wear [4,7,12,15,23]. Regarding surface treatment and cementation, third-and fourth-generation zirconia lack adhesiveness and need to undergo the same surface treatments to improve the surface roughness [25][26][27][28][29]33,50,51]. Alammar et al. [52], in 2022, conducted a systematic review on the bonding of high translucency zirconia and concluded that the bonding protocols already applied on conventional zirconia (particle abrasion treatment, MDP primers, and resin cements) provide the best results also on this type of zirconia, as they provide a long-term adhesive bond without compromising the physical properties.
Most of the studies that analyze the ageing of zirconia ceramics focus on the study of the influence of changes generated by hydrothermal conditions in the oral environment. These changes are influenced by the phase transformation of the zirconia and at the same time the affectation caused by crack propagation in the fracture, which is studied by using compressive stress. The aging resistance is higher in third-than fourth-generation zirconia due to the cubic phase percentage [4,7,12,17,32,38,42]. No differences were found in the marginal accuracy and internal fit of zirconia materials in the third and fourth generation [24,30,46]. Nevertheless, in recent years, especially after the emergence of translucent zirconia, there has been an increase in research on the cyclic fatigue of these materials to fill the gap in the literature on the dynamic ageing of these materials. As commented by Baldi et al. [53] in 2022, it is observed that there is a lower strength and marginal sealing of high translucent zirconia compared with zirconia-reinforced lithium silicate under cyclic fatigue, so there is still a need for further research.
Despite the previous efforts that have been devoted to the study of this material, there is evidently a lack of a comprehensive understanding of the chemical structure. An absence of unified terminology and several strategies adopted by manufacturing companies to improve the characteristics of this ceramic system originate a gap in the knowledge that allows mistakes when clinicians and lab technicians are using Y-TZP as a ceramic material. A limitation of this review of the literature is that the behavior of new generations of zirconia under cyclic fatigue has not been analyzed. Future research needs to analyze the cyclic fatigue and the clinical behavior of this material.

Conclusions
Zirconia ceramics are widely used in the biomedical field. Regarding the physicochemical features and optical and mechanical properties, the expectancy of an enhancement of the mechanical properties with a combined reduction in its light optical properties when comparing the third-and fourth-generation zirconia was confirmed. The fourth-generation zirconia material 4Y-TZP shows better mechanical properties but less percentage of translucency. Clinicians should be careful when zirconia material is their choice when performing fixed restorations. Translucency is not always an advantage; if discolored stumps were the base of their restoration, translucent zirconia materials would become disadvantageous.

Conflicts of Interest:
The authors declare no conflict of interest.