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Kocjan, Andraž, Mirt, Tadej, Kohal, Ralf-Joachim, Shen, Zhijian and Jevnikar, Peter (2021) Zirconia Ceramics:
Clinical and Biological Aspects in Dentistry. In: Pomeroy, M. (ed) Encyclopedia of Materials: Technical Ceramics
and Glasses, vol. 3, pp. 817–832. Oxford: Elsevier.
http://dx.doi.org/10.1016/B978-0-12-818542-1.00051-5

© 2021 Elsevier Inc. All rights reserved.

 Author's personal copy

Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

Andraž Kocjan, Department for Nanostructured Materials, Jožef Stefan Institute, Ljubljana, Slovenia
Tadej Mirt, University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
Ralf-Joachim Kohal, Medical Center - University of Freiburg, Center for Dental Medicine, Department of Prosthetic Dentistry, Faculty
of Medicine, University of Freiburg, Freiburg, Germany
Zhijian Shen, Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden
Peter Jevnikar, University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia
r 2021 Elsevier Inc. All rights reserved.

Background

Fixed partial dentures (FPDs) produced from modern dental materials are used in dental medicine to restore anatomic form and
function, and/or esthetics. Traditional metal-ceramic restorations have had acceptable success rates, but are limited by pertinent
concerns such as tissue compatibility and esthetics. Successful emergence of 3 mol% yttria partially-stabilized tetragonal zirconia
(3Y-TZP) bioceramics in orthopedics gained an immense interest in dentistry in the early 90s. Owing to 3Y-TZP's high esthetics,
chemical inertness, exceptionally high strength and toughness for a ceramic material, it advocated the replacement of traditional
porcelain veneered metal-ceramic FPDs. It followed that in the past three decades, there have been profound advances in the
application of 3Y-TZP in restorative dentistry further expanding clinical indications of tooth-colored, all-ceramic systems to crowns
and bridges, root posts and even implants (Piconi and Maccauro, 1999; Denry and Kelly, 2008).
3Y-TZP ceramics exhibit high flexural strength (900
1200 MPa), fracture toughness (4
6 M Pam–1), and a lower Young’s modulus
(210 GPa) compared to alumina (340 GPa) (Piconi and Maccauro, 1999). Therefore, it is suitable to serve as a core material and withstand
high stresses produced in the posterior dentition, where masticatory forces are higher due to the masticatory muscle attachment.
3Y-TZP's high strength and fracture toughness are governed by the stress-induced tetragonal-to-monoclinic (t-m) transforma-
tion toughening mechanism, where under applied stress the metastable tetragonal phase (grains) transforms to monoclinic. This
causes volumetric expansion and creates compressive stresses that oppose the tensile stress in the vicinity of a propagating crack tip
(Fig. 1(a)) (Butler, 1985). Because of this toughening mechanism, the 3Y-TZP ceramic was labeled as “ceramic steel” (Garvie et al.,
1975; Gupta et al., 1978). 3Y- TZP's mechanical properties are far superior to other dental (glass) ceramics, such as feldspathic
porcelain, lithium disilicate, alumina, allowing it to be also used in high load-bearing areas.
Pure zirconia (ZrO2), an oxide ceramic polymorphic system, exhibits three different crystal lattice types under atmospheric
pressure. At temperatures higher than 23701C, zirconia occupies cubic lattice. Between 11701C and 23701C, zirconia is tetragonal,
and below 11701C the lattice is monoclinic. Upon cooling, the t-m phase transition is accompanied by 3
5 vol% increase, which
facilitates cracking of the sintered bulk. The spontaneous phase transformation can be avoided by modifying the composition with
traces of other oxides, such as MgO, CaO and CeO2. Such doping strategy results in partial stabilization of the tetragonal phase at
room temperature, and thus cracking upon cooling is prevented and the stress-induced transformation toughening installed
(Hannink et al., 2004). Generally, biomedical grade zirconia used in dentistry is doped with 3 mol% of yttria (Y2O3) and a small
amount of alumina (0.25 wt%). Such 3Y-TZP ceramics are characterized by fine-grained microstructures (0.3–0.5 mm) (Fig. 1(b)),
where inclusions of distinct alumina grains can be found in the matrix (Samodurova et al., 2015b).

Fig. 1 (a) Schematics of stress-induced t-m transformation toughening around an advancing crack, where transforming tetragonal particles to
monoclinic symmetry form a process zone exerting compressive strain. (b) SEM micrograph of polished and thermally etched surface of the 3Y-
TZP sintered for 2 h at 14501C. Darker faceted grains are alumina inclusions. (c) Schematics of the ageing process in a cross-section showing
spontaneous nucleation and growth, stress-corrosion-type mechanism of t-m transformation, leading to microcracking and stresses to the
neighboring grains. Reproduced from (a) Butler, E.P., 1985. Transformation-toughened zirconia ceramics. Mater. Sci. Technol. 1, 417–432.
doi:10.1179/mst.1985.1.6.417, Copyright Taylor & Francis. (c) Chevalier, J., 2006. What future for zirconia as a biomaterial Biomaterials 27,
535–543. doi:https://doi.org/10.1016/j.biomaterials.2005.07.034, Copyright Elsevier.

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818 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

3Y-TZP is pressure-less sintered at relatively low sintering temperatures (1350
15001C) to produce full density (Z99.5%). The
addition of Y3 þ replaces Zr4 þ in the crystal lattice creating oxygen vacancies that maintain the tetragonal phase partially stable at
room temperature after sintering (Chevalier et al., 2009). A small amount of alumina is added to 3Y-TZP to prevent yttria segregation,
which results in improved ageing resistance and reinforces grain boundaries (Matsui et al., 2006; Samodurova et al., 2015a).
However, the long-term stability of the 3Y-TZP ceramics is known to be susceptible to a superficial ageing phenomenon the so-
called low-temperature degradation (LTD); a spontaneous t-m transformation of 3Y-TZP's surface in an aqueous environment at
moderate temperature, including body temperature. At the onset of the present millennium, several hundreds of 3Y-TZP femoral
heads failed in a short period following implantation, with the origin of the fracture indirectly associated with LTD (Haraguchi
et al., 2001). Since then, numerous studies have been performed to investigate the mechanisms and kinetics of LTD.
It was found out that the t-m transformation is temperature-dependent and diffusion-controlled, accompanied by extensive
microcracking, and surface uplifting, which ultimately leads to strength degradation (Fig. 1(c)) (Chevalier, 2006). The LTD process
was found out to be a grain-size dependent stress-corrosion-type mechanism starting at the 3Y-TZP's surface and proceeding into
the bulk (Kosmač et al., 2012; Hallmann et al., 2012). It is sensitive to the differences in the starting materials and process additives
(co-dopants) (Samodurova et al., 2015a; Zhang et al., 2016a; Bučevac et al., 2017) and the materials’ processing-related prehistory
(grinding or sandblasting; Kosmac et al., 1999; Chintapalli et al., 2013; Cotič et al., 2016). Moreover, some studies showed how the
highly distorted tetragonal zirconia grains and pre-existing monoclinic zirconia in the ground and air-particle abraded surfaces
hindered the t-m transformation during ageing (Kosmač et al., 2008).
Deville and Chevalier established a relationship between the amount of the transformed monoclinic phase and the accelerated
hydrothermal ageing time in an autoclave at 1341C in distilled water to estimate the equivalent ageing time under “in vivo” conditions
based on the results obtained with retrieved 3Y-TZP femoral heads (Chevalier et al., 2007; Chevalier and Gremillard, 2009). A postulation
was made that one hour of ageing in vitro corresponds to about three years “in vivo”. However, as stated above, 3Y-TZP ceramics may
differ substantially in their fabrication method and properties, as well as in clinical conditions and it was later shown by Keuper et al.
(2014) that such approximation of the ageing process to room temperature can result in important underestimation. However, at the
moment, there are no obvious clinical indications that the LTD of 3Y-TZP used in dentistry would represent a severe concern.
In the beginning, the 3Y-TZP frameworks were produced by costly and time-consuming precise hard-milling of densely sintered
and hot isostatically pressed 3Y-TZP blocks. Later, direct oversize milling of pre-sintered 3Y-TZP blanks has become increasingly
popular in dentistry and is now the most common method in the fabrication of 3Y-TZP FPDs (Raigrodski, 2005). In this
manufacturing technology, the die or a wax pattern is scanned, and/or enlarged restoration is digitally designed by computer
software (CAD), and a pre-sintered ceramic blank is oversize-milled by computer-aided machining (CAM). The restoration is then
sintered to full density. However, the process of milling of preformed zirconia blocks generates a lot of waste material that is
environmentally unfriendly; therefore, new methods of zirconia fabrication have evolved recently.

Biomedical Grade Zirconia in Fixed and Removable Prosthodontics

Biomedical grade 3Y-TZP was initially used for the fabrication of orthodontic brackets (Keith et al., 1994), root canal posts
(Meyenberg et al., 1995) and implant abutments (Glauser et al., 2004). Afterwards, 3Y-TZP emerged as a strong and tough core
material in all-ceramic FPDs. Nowadays, 3Y-TZP ceramics is a material of choice for the entire spectrum of fixed restorations,
including inlays, onlays, single crowns, multi-unit bridges, and implant-supported restorations (Guess et al., 2012). It may also
successfully serve as an alternative option to implants and/or bridges of replacing missing lateral incisors in adolescents and young
adults with a cantilevered resin-bonded fixed dental prosthesis (RBFDP) and thereby avoiding more aggressive treatment (Fig. 2).
In addition, several indications in removable prosthodontics exist, where 3Y-TZP ceramics is successfully implemented. There is
a strong clinical evidence of double crown system, where primary crowns are milled from 3Y-TZP ceramics and secondary crowns
galvano-formed in gold (Fig. 3(a)). This clinical protocol has been introduced by Weigl and Lauer (2000). The retention
mechanism of the 3Y-TZP-galvano system is based primarily on the very precise manufacturing of both crowns. The template for
the galvano-forming of the secondary crown is the primary ceramic crown itself. Consequently, a gap not exceeding
5 mm can be achieved. Retention of the system is therefore primarily based on capillary pressure and adhesion between the crowns.
This way predictable and long-term stable clinical success can be achieved. Retention of the system also depends on the conical
crowns’ surface area and surface roughness of the materials. The proposed protocol includes intraoral bonding of the secondary
galvano-crowns to the tertiary metal framework. This concept has also been extended to tooth-implant prosthetic rehabilitations
(Fig. 3(a)), where custom made zirconia implant abutments serve as primary crowns (Brandt et al., 2019).
Bar retained implant dentures are often designed in edentulous patients with head and neck cancer. This way, good denture
retention and stability can be achieved. In the past, bars were cast from Co-Cr alloys. Currently they are milled from metal blocks in a
CAD-CAM process. As there is a common trend to minimize metals in the oral cavity 3Y-TZP milled bars are indicated (Fig. 3(b)).

Bonding to Dental Zirconia Ceramics

The evolution of new generations of dental adhesives that promote a reliable bond between two chemically diverse materials, i.e.,
dentin or enamel and composite resin has enabled to replace conventional, retentive-based cementation techniques with adhesive
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Zirconia Ceramics: Clinical and Biological Aspects in Dentistry 819

Fig. 2 A clinical case replacing lateral incisors resin-bonded fixed dental prosthesis (RBFDP): (a) before the prosthetic rehabilitation, (b) veneered
zirconia dental prosthesis and (c) after the prosthetic rehabilitation.

Fig. 3 3Y-TZP ceramics applied in removable prosthodontics: (a) Primary telescopic crowns on abutment teeth and implants (lower left).
Secondary crowns are galvanoformed via electrolytic gold deposition (upper left) and bonded to tertiary framework (lower right). (b) 3Y-TZP
screw-retained CAD/CAM milled bar (left) in the edentulous lower jaw for the retention of implant-supported denture (lower right).

bonding procedures of FPDs. To achieve a durable bond between 3Y-TZP ceramics and bonding agent, several methods have been
proposed. Numerous “in vitro” and “in vivo” studies have been conducted to resolve the durability and strength of the resin bond
(Kern, 2015), since chemical methods such as acid-etching and silanization, that are successful in luting of silicate ceramics, proved to
be ineffective to promote adhesion of composite luting agents to zirconia surface due to the high chemical inertness and the absence
of siliceous phases in polycrystalline zirconia matrix. It followed the advent of employing surface roughening of zirconia by air-
particle abrasion (APA) with alumina particles also called sandblasting (Fig. 4(a)), which enhances the mechanical interlocking,
which is the most commonly used surface treatment (Shahin and Kern, 2010). APA parameters, such as alumina particles size
(30–250 mm), blasting pressure (0.05
0.6 MPa) and blasting distance, have been studied immensely. The interchange of these
parameters has led to a consensus that APA with 50–110 mm alumina particles at 0.25 MPa is effective in cleaning and roughening
zirconia ceramics as it most likely removes contaminants from ceramic surface and exposes a fresh bonding surface. The APA could
theoretically lead to mechanical degradation of zirconia ceramics by producing microcracks and subsurface damage. Many authors
have questioned the use of aggressive treatments of zirconia; however, several studies on the other hand demonstrated that APA
improved the mechanical strength of 3Y-TZP presumably via transformation toughening mechanism irrespective of the blasting
pressure (Kosmac et al., 1999; Aurélio et al., 2016; Chintapalli et al., 2014; Cotič et al., 2017).
It is fundamental to combine APA with the use of chemical promoters, capable of improving adhesion. Primers contain
organophosphate monomers, including 10-MDP (10-Methacryloyloxydecyl Dihydrogen Phosphate), present a terminal functional
group with phosphoric acid, which reacts with zirconia and forms P-O-Zr bonds. The other end of the molecule exposes a vinyl
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820 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

Fig. 4 SEM micrographs showing (a) APA modified 3Y-TZP surface; and nanostructured alumina coating deposited on the as-sintered 3Y-TZP
surface: (b) coatings` topography; (c) cross-sectional view (1 – coating; 2–3Y-TZP substrate). Reproduced from (b, c) Malgaj, T., Kocjan, A.,
Jevnikar, P., 2020. The effect of firing protocols on the resin-bond strength to alumina-coated zirconia ceramics. Adv. Appl. Ceram. Struct. Funct.
Bioceram. 119, 267–275, Copyright Taylor & Francis.

terminal group, which allows the copolymerization with the resin. Today 10-MDP-based cements and primers are used for this
purpose. The low viscosity of 10-MDP primers favors penetration into surface micro-porosities and bond resistance over time. In
the other hand, 10-MDP-based viscous cement can bind to zirconia but are not able to, alone, maintain stable long-term adhesion,
which is more susceptible to hydrolysis (Russo et al., 2019).
Among surface roughening techniques the APA using silica modified alumina particles (i.e., the so-called Rocatec system) has
been developed not only to enhance the surface roughness of zirconia but also to provide free silica groups to form the bond with
the silane coupling agent. Although this bond is according to thermodynamic calculations more resistant to hydrolysis than the
bond between zirconia and 10-MDP (Xie et al., 2016), the effectiveness of APA using silica modified alumina particles has been
questioned (Kern, 2015).
An alternative solution to the adhesion problem has recently been proposed by a non-invasive functionalization of the zirconia
surface, by applying a thin (200–400 nm) nanostructured alumina coating consisting of interlocked 2D lamellae or nanosheets
exhibiting a large surface area by which bonding to the substrate is significantly improved. The coating shows a uniform thickness
and good surface coverage (Fig. 4(b) and (c)). It is almost insensitive to thermocycling and has the potential of durable
improvement of the adhesive bond between the coated core material and the dental cements by a factor of 2–4, depending on the
surface roughness of the substrate, the dental cement and the firing protocol used (Jevnikar et al., 2010, 2012; Malgaj et al., 2020).

Delamination and Chipping of the Veneered Overlayer

Chipping and fracture of veneering porcelain are commonly reported in all-ceramic zirconia restorations, which is reportedly
higher than the chipping rate of porcelain bonded to metal-ceramic restorations. This could be ascribed to the higher chemical
inertness, less favorable wetting ability and considerably lower thermal diffusivity of 3Y-TZP ceramics, as compared to metals. The
thermal expansion mismatch and cooling rate-induced tempering of zirconia framework and veneering porcelain contribute to the
formation of high tensile subsurface residual stresses in layers of porcelain which may result in unstable crackings or chippings,
that are presumably contact-induced (Swain, 2010). Minor chipping damages can be temporarily repaired (Özcan, 2015; Özcan
et al., 2013), but in most cases, the whole restoration has to be replaced. Other causes for failures of all-ceramic FPDs are
debonding, i.e., loss of coherence between the restoration and the abutment tooth, fracture of the framework, and delamination of
the veneering porcelain. The fracture is due to the locally exceeded stress concentration in the framework, while the debonding and
delamination are associated with the chemical inertness of the core material. Also worth mentioning is the problem that not only
dental clinicians but also the producers of the zirconia blanks are facing. This is the lack of relevant standards and recommen-
dations regarding the physical and chemical properties of 3Y-TZP ceramics for dental applications, i.e., considering specific clinical
conditions in the aggressive environment of the oral cavity.
Aside of the several unsuccessful attempts to overcome the chipping problem by hot pressing or CAD/CAM machining and
subsequent joining with 3Y-TZP core, the community geared toward a more radical but practical solution, i.e., toward porcelain-
free, monolithic zirconia crowns and bridges, despite the risk of higher wear of the opposing tooth enamel and the direct exposure
of the ageing-susceptible zirconia surface to the aggressive wet environment of the oral cavity. Nevertheless, the introduction of
this conceptual idea was largely accepted in the dental community leading to wide production and application of the monolithic
or full-contour zirconia ceramics for FPDs.

Translucency
In the quest towards highly translucent but stronger than glass-ceramics, new generation zirconia grades have been developed and
commercialized recently. Due to the improved esthetics, monolithic restorations with only a thin, few microns thick, glaze coating
layer (in visible regions) can be realized, allowing a further reduction of the restoration thickness. Moreover, pre-sintered blocks
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Zirconia Ceramics: Clinical and Biological Aspects in Dentistry 821

are both available as pre-shaded in several tonalities and multilayered with gradients of chroma and different degrees of trans-
lucency. The benefit of the so-called “monolithic/full-contour” restorations allow decreasing the risks of chipping, the prosthetic
cost and production time.
Zirconia ceramics with increased translucency can be realized in several ways: (1) refining the microstructure using (a) wet
shaping techniques of zirconia nanopowders (Liu et al., 2016) and/or (b) advanced sintering strategies (Xiong et al., 2014; Kocjan
et al., 2015) and specific sintering additives, (2) grain boundary (microstructural) engineering by co-doping to control dopant
segregation (Zhang et al., 2015) (3) increasing the amount of cubic phase that ultimately increases grain size that also possesses
considerably lower optically anisotropy (birefringence) (Zhang and Lawn, 2018).
All these strategies can be found in different commercial zirconias with a claimed improved translucency. In particular, we may
now find novel yttria fully-stabilized grades with a higher content of yttria. However, not only do these microstructural variations
imply substantial improvements in the overall optical performance of zirconia, but they also inevitably introduce noticeable
changes in its mechanical properties and long-term stability (Camposilvan et al., 2018).

Elastic Modulus and Hardness Mismatch

3Y-TZP' hardness (12–14 GPa) is B50% lower than of alumina, which is a clear advantage over alumina in the adjustments of
occlusal surfaces of FPDs by grinding, finishing or polishing. In addition, the importantly lower hardness of zirconia should also
reflect in a less severe impact of occlusal wear of opposing teeth, where the average hardness of enamel was reported to be between
3.4 and 4.8 GPa (Cuy et al., 2002; Willems et al., 1993). Moreover, due to the ability of zirconia ceramics to be finely polished, the
occlusal wear appears to be negligible. The observed wear is even less damaging than in the case of feldspathic porcelain, lithium
disilicate ceramics and enamel to enamel attrition (Chong et al., 2015; Lawson et al., 2014; Passos et al., 2014; Wang et al., 2012;
Zhang et al., 2019b). Such a positive outcome might be related to the ability of quasi-plastic deformation under mechanical wear
as a result of evolved subsurface shear stresses triggering the t-m phase transformation (Luthardt et al., 2004).
Another advantage of zirconia in relation to alumina is that its elastic modulus is much lower than that of alumina (200 GPa
versus 380 GPa), which implies lower elastic stresses between the natural dentine and the prosthetic work. Still, the elastic
modulus of zirconia is considerably higher than natural dentin that is demonstrated with posts-cores in endodontically treated
teeth with insufficient tooth structure. Zirconia posts were introduced to replace esthetically unpleasant metal posts (Meyenberg
et al., 1995). However, the high elastic modulus of zirconia posts causes stress to be transferred to the less rigid dentin, thereby
resulting in vertical root fractures (Mannocci et al., 1999). A significantly improved fracture resistance and predominantly favorable
failure modes were manifested, when restoring teeth with a prefabricated zirconia post and core system with a wide, retentive
coronal shape and when the root post space is designed with 1–2-mm deep internal plateau (Fig. 5) (Jovanovski et al., 2019).

Biocompatibility
Over the years, the tissue compatibility of zirconia ceramics has been evaluated extensively “in vivo” and “in vitro”. There has been
an abundance of in vitro tests performed on different physical forms of zirconia (e.g., powders and dense ceramics), that showed
no local or systemic cytotoxic effects or adverse reactions associated with zirconia. The “in vivo” bone formation adjacent to
zirconia and the inflammatory response to zirconia have been shown to be satisfactory. However, initial results frequently showed

Fig. 5 (a) The internal plateau preparation in an extracted tooth mounted in resin and (b) after inserting the prefabricated zirconia post and core
system in post space. Reproduced from (b) Jovanovski, S., Cotič, J., Kocjan, A., Oblak, Č., Jevnikar, P., 2019. Fracture resistance of endodontically treated
maxillary incisors restored with zirconia posts: Effect of the internal plateau preparation. Adv. Appl. Ceram. 118, doi:10.1080/17436753.2018.1508625,
Copyright Taylor & Francis.
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822 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

the formation of connective tissue at the bone-ceramic interface before the implementation of surface roughening of zirconia
implants improved bone-implant contact. Furthermore, microorganisms seem to adhere to zirconia to the same extent as to other
materials. One can conclude that minor observed irritations may be attributed to mechanical irritation, e.g., from roughened
surfaces. The mutagenic and cancerogenic in vitro tests on zirconia ceramics also showed the dearth of any similar reactions and no
emergence of tumor cells (Piconi and Maccauro, 1999).
Zirconium is derived from Zircon (ZrSiO4) or Baddeleyite. These minerals may contain a small amount of radioactive
impurities. Thus, using zirconia in biomedical applications raised the question of the materials' safety. Zirconia-based medical
devices are strictly regulated for radioactive decay (max. 0.2 Bq/g) by the ISO 13356 standard. The activity of uranium-radium and
thorium radionuclides in different types of zirconia bioceramics was investigated by Porstendörfer et al. (1996). They showed that
the estimated effective dose found was below the dose limit of 1 mSv/year. It was recently shown that the radioactive potential of
zirconia dental ceramics is negligible compared to radioactive appliances in our environment (Bavbek et al., 2014) obviously
posing no risk to the patient.

Full-Contour Monolithic Zirconia and Minimally Invasive Dentistry

The development and commercialization of translucent zirconia dental ceramics allowed fabrication monolithic FPDs with
innumerable advantages; these are the elimination of chipping risk, the satisfactory mechanical properties (compared to leucite
and lithium disilicate glass-ceramics), the possibility of employing the CAD-CAM processing workflow (greater standardization
and quality of results, with cost reduction), the possibility of manufacturing of thinner FPDs, and a more conservative dental
preparation restricting within the principles of minimally invasive dentistry (Zhang and Lawn, 2018).

High-Translucency Zirconia (4Y, 5Y) Grades

Traditional partially-stabilized zirconia ceramics doped with 3 mol% yttria (3Y-TZP) have been shown to withstand the stresses
superior to the highest biting forces. In the last few years, the progress in the manufacturing of zirconia ceramics with improved
translucency and esthetic features have established new generations of high-, super- and ultra-translucent zirconia ceramics. This was
mainly achieved by modifying the t-ZrO2 matrix by adjusting the concentrations of minor elements, such as reducing the amount
of alumina (Al2O3) and, more importantly, increasing the molar percentage (concentration) of yttria (Y2O3), up to 5 mol%, to
the extent allowing its use in a monolithic form, e.g., single crowns, onlays, inlays, anterior cantilever resin-bonded bridges
(Zhang and Lawn, 2018).
With that in mind, different zirconia generations have evolved historically. Zirconia materials can currently be divided into four
types or generations according to their mechanical and optical properties (Güth et al., 2019).

Biomedical grade 3Y-TZP

1st generation of dental zirconia is represented by the conventional biomedical grade 3Y-TZP. Since it is a birefringent material, the
optical properties of 3Y-TZP are greatly influenced by the structure of the grain boundaries. Typically, the alumina content in this
family of zirconia ceramics is around 0.25%, which is concentration high enough to facilitate the formation of isolated alumina
grains in the 3Y-TZP matrix during sintering. As a consequence, light transmittance is hampered resulting in a high opacity and
compromised visual appearance. Thus, 1st generation 3Y-TZP zirconia is not suitable material for monolithic use. In the past years,
the main focus was to improve the optical properties, especially increasing the translucency.

Highly-translucent 3Y-TZP
A 2nd generation of highly-translucent zirconia ceramics was introduced around 2013 – a 3Y-TZP variant with lowered amount
(B0.05 wt%) of alumina in the matrix. This way, the alumina grains do not form anymore in the ceramic matrix (Samodurova
et al., 2015b) resulting in a higher level of light transmission. The flexural strength remained high, and the in-vitro stability was
sufficient allowing it to be predominantly used as a framework material for one- and multi-unit FDPs.

Ultra-translucent zirconia (stabilised with 5 mol% yttria)

The 3rd generation of dental zirconia ceramics was developed in 2015 labeled as ultra-translucent and is recommended for the
production of single-tooth crowns and FDPs with up to three units in the anterior region. The increase of the yttria (Y2O3) content
up to 5 mol% substantially increases the translucency (Fig. 6(a)), mainly because the resultant ceramic material with such an
amount of yttria is closer to a more optically isotropic cubic symmetry form (or t``-ZrO2 with a much lowered tetragonality
(Fujimori et al., 2001)). The matrix grains are larger and less birefringent than the tetragonal grains; therefore, the light passes fewer
boundaries that are also plan-parallel causing lower light scattering on passing through the material (Krell et al., 2009). Besides a
higher degree of translucency, the increase of the yttria content ultimately provides a genuinely LTD-resistant zirconia ceramics
(Zhang et al., 2016b).
The tremendously profitable improvements of gained by increasing the yttria content undoubtfully have a deleterious trade-off,
i.e., they are mechanically weaker ceramic material due to the absence of the t-m transformation toughening (Fig. 6(b)). Compared
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Zirconia Ceramics: Clinical and Biological Aspects in Dentistry 823

Fig. 6 (a) Comparison of translucency of various zirconia grades and lithium disilicate (LS2) ceramics in 0.5-mm thickness. (b) Weibull plots
showing data for four-point bending strength of various grades of zirconia ceramics. Reproduced from (b) Zhang, F., Reveron, H., Spies, B.C.,
Van Meerbeek, B., Chevalier, J., 2019a. Trade-off between fracture resistance and translucency of zirconia and lithium-disilicate glass ceramics for
monolithic restorations. Acta Biomater. 91, 24–34. doi:10.1016/j.actbio.2019.04.043, Copyright Elsevier.

to the lithium disilicate, the translucency of the 3rd zirconia generation is slightly lower, but the flexural strength and fracture
toughness are higher (Zhang et al., 2019a).

Super-translucent zirconia (stabilised with 4 mol% yttria)

Most recently, in 2017, the 4th generation of zirconia, known as super-translucent, was announced to increase the indication range
for monolithic zirconia restorations, such as short-span multi-unit FDPs in the premolar region. Compared to the 3rd generation,
the yttria content was reduced to 4 mol% (t`-ZrO2 polymorph), which led to an enhancement of the mechanical properties with a
combined reduction in its optical properties. It is LTD resistant material owing to the absence of t-m process, whereas the
improved strength and toughness in comparison to 5 mol% variant originate from the process of ferroelastic domain switching
typically encountered in t`-ZrO2 (Hannink et al., 2004; Virkar and Matsumoto, 1986; Mercer et al., 2007).

Glazing and Staining

Milling of a presintered blank to full-contour has been established for monolithic zirconia restorations (Fig. 3(b)). In this way, the
common use of a thick ceramic veneer layer can be avoided, but a thin stain and glaze coating layer still need to be applied to
realize the overall appearance of monolithic crowns, inlays, onlays or veneers. Fine glass powder that may contain metal oxides as
pigments is applied on zirconia surface and subsequently fired at temperatures between 550 and 9001C. The characteristic and
smooth esthetic layer of overglaze is formed superficially on zirconia restoration. Glazing does appear to protect the first two
zirconia generations against LTD in a humid oral environment (Oblak et al., 2017).
However, it has been shown that glazed zirconia increases wear of antagonist teeth and also of restoration itself; the extent of
wear of the antagonists was reported to be even higher than for the polished zirconia (Lawson et al., 2014). Therefore, the occlusal
surfaces of monolithic restorations in posterior regions should not be altered with glazing, unless esthetics is preeminent and that
exposed, unglazed surfaces are carefully polished before use in order to reduce the wear of the enamel of the opposite teeth
(Liu et al., 2016).
Moreover, it was also shown that after long-term thermal and mechanical fatigue the glaze layer might represent the weakest
link for crack initiation and propagation, which can dramatically affect the strength of FPDs. Studies have shown that the glazing
significantly reduces the flexural strength of high translucent zirconia and that LTD decreased the flexural strength of glazed
translucent (Nam and Park, 2018) and super-translucent zirconia (Lai et al., 2017) indicating accumulating stress areas in the
surface layers of the material. Furthermore, in a fractographic study of Oblak et al., it was clearly indicated that the flaws and
imperfections in the glaze layer or the glaze-zirconia interface depict the weakest spot of the glazed zirconia restorations where the
initiation of the fracture presumably originates (Fig. 7) (Oblak et al., 2017).

Self-Glazed Zirconia Ceramics

A new grade of self-glazed zirconia ceramics, based on 3Y-TZP system, with natural-looking, enamel-like surface finish has been
recently developed to address the above-mentioned risks of glazing (Shen et al., 2017). It requires no further need for veneering or
glazing, thereby evading fragile interfaces (Fig. 8(a)). Moreover, beside rationalization, i.e., abolishing the need for glazing step
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824 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

Fig. 7 SEM fractographic analysis of the monolithic 4-unit zirconia bridge overlaid with thin glaze layer after fracture in bending. (a) Black arrows
are indicating on the formed coarse microstructural hackle lines running away from the fracture mirror. (b) Inset at from (a). Dotted white arrows
are indicating on a series of wake hackles propagating from the entrapped bubbles in the glaze. Reproduced from (a) Oblak, C., Kocjan, A.,
Jevnikar, P., Kosmac, T., 2017. The effect of mechanical fatigue and accelerated ageing on fracture resistance of glazed monolithic zirconia dental
bridges. J. Eur. Ceram. Soc. 37, 4415–4422. doi:10.1016/j.jeurceramsoc.2017.04.048, Copyright Elsevier.

Fig. 8 (a) Intraoral view after the treatment with self-glazed zirconia crowns on the upper incisors and canines and (b) virtual digital design of
the crowns. Reproduced from (b) Wu, Z., Shi, A., Liang, Q., et al., 2020. Aesthetic restoration of anterior teeth with monolithic self-glazed zirconia
crowns via a completely digital workflow: A clinical case report. Adv. Appl. Ceram. 119, 291–296. doi:10.1080/17436753.2019.1690847, Copyright
Taylor & Francis.

that is done in a dental laboratory, the precision additive 3D gel deposition fabrication allows full digitalized reconstruction
approach (Fig. 8(b)), since it can be applied with slightest clinical adjustment (Liu et al., 2016).
The reliability of self-glaze zirconia material was shown comparatively strong to conventional zirconia materials in crown and
bridge restorations (Zhang et al., 2017). Different from the rougher CAD/CAM milled zirconia, the self-glazed zirconia has very
smooth surfaces that prevent excessive wear of antagonist teeth, which is similar to the polished surface. The improved esthetic
appearance of self-glazed zirconia ensures its potential for direct clinical uses (Liu et al., 2016).

Zirconia Oral Implantology

Oral implants to replace lost teeth were a big step forward in oral rehabilitation. With oral implants, the patients’ comfort can be
increased with implant-supported/-retained fixed/removable prosthesis (Heydecke et al., 2005). Titanium is considered to be the
material of choice for the fabrication of oral implants (Howe et al., 2019). However, due to certain reasons, e.g., patient request,
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Zirconia Ceramics: Clinical and Biological Aspects in Dentistry 825

Fig. 9 (a) A Y-TZP one-piece implant (ceramic_implant, Vitaclinical, Bad Säckingen, Germany), (b) an ATZ one-piece implant (Ziraldent, Metoxit,
Thayngen, Switzerland) and (c) an ATZ two-piece implant (Zeramex XT, Dentalpoint AG, Spreitenbach, Switzerland).

esthetic concerns, health issues like titanium hypersensitivity, and more, zirconia ceramic implants are also being used in oral
implantology today (Balmer et al., 2020; Kohal et al., 2020).

Zirconia-Based Implant Materials

In the beginning of the ceramic implant era, alumina was applied as a substrate for implant fabrication (Schulte, 1981). However,
this material was too weak to withstand oral function over a longer period of time (De Wijs et al., 1994). Furthermore, bone
apposition (i.e., osseointegration) onto that material was not predictable. In the search of a “better” tooth-color-like ceramic material,
zirconia was evaluated. Today, the ceramic materials which are possibly to be used for the fabrication of oral implants are 3Y-TZP
(Balmer et al., 2018), ATZ (Spies et al., 2015), Ce-TZP (Lopez-Píriz et al., 2017) or composite ceramics (Altmann et al., 2017). In
clinical investigations (Pieralli et al., 2017; Roehling et al., 2018), the dominant zirconia material so far is 3Y-TZP (Fig. 9(a)) followed
by ATZ (Fig. 9(b)). Composite materials such as ceria-stabilized zirconia–alumina–aluminate composite ceramics are in the
experimental stage.

Implant Systems – One/Two-Piece

Initially, zirconia ceramic implants were designed as one-piece implants because of fabrication and stability reasons. Therefore,
most of the clinical investigations published so far were evaluating one-piece zirconia implants. The advantages of the one-piece
implants are their excellent stability (high fracture resistance), good short- to mid-term clinical performance, low marginal bone
loss, no abutment screw loss and no microgap between abutment and implant body possibly serving as bacterial reservoir leading
to marginal periimplant soft tissue inflammation. The disadvantages of the one-piece implants are found in their versatility. The
adaptation of the abutment part to the clinical situation is only possible through grinding which in the end might lead to stability
reduction (Fig. 10).
The correct prosthetic position can be problematic, especially in areas with an increased inclination of the alveolar ridge. The
prosthetic reconstructions of one-piece implants are generally regarded as limited. Due to the mentioned shortcomings of one-
piece implants, two-piece implants were developed (Fig. 9(c)). They present an improved prosthetic versatility with the application
of angulated abutments if needed. The reconstructions are usually screw retained (gold alloy, titanium alloy, carbon-reinforced
PEEK) and can therefore be removed for any reasons without destroying those (Fig. 11).

Implant Stability
An expressed concern with ceramic implants is their long-term stability. Therefore, it is of utmost importance to evaluate fracture
resistance in-vitro before launching an implant product on the market. Numerous reports have been published on the in-vitro
stability of one- and two-piece zirconia oral implants which have been evaluated in a systematic review by Bethke and coworkers
(Bethke et al., 2020). From the included and evaluated publications, the authors came to several conclusions: one-piece implants
are obviously more stable than two-piece implants. Regarding the material, implants made from 3Y-TZP seem to be less
stable than implants fabricated from ATZ. In a systematic review on clinical studies, Roehling et al. (2018) found regarding implant
stability that only one out of 510 commercially available implants evaluated fractured. This translates into an overall fracture rate
of 0.20% which is comparable to the fracture rate of titanium implants (0.18%) (Jung et al., 2012).
One-piece implants with a diameter of 4 or more mm seem to be stable enough to survive at least 5 years of clinical function
(Kohal et al., 2020; Balmer et al., 2020). From the in-vitro investigations, these implants survived long-term artificial chewing and
it is anticipated that these implants also withstand long-term clinical load.
Zirconia ceramic implants made from 3Y-TZP are prone to LTD (see above) and show t-m transformation already in the as-
delivered state or after hydrothermal ageing (Fig. 12). LTD was initially discussed to reduce the stability of zirconia. However,
regarding zirconia ceramic implants that have been hydrothermally treated and have shown (superficial) transformation, no
decrease in fracture stability (Sanon et al., 2013; Spies et al., 2018, 2017) could be observed.
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826 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

Fig. 10 (a) An ATZ one-piece implant in the anterior upper region after adaptation to the prosthetic needs. (b) Implant reconstructed with an
all-ceramic crown (Ziraldent, Metoxit, Thayngen, Switzerland).

Fig. 11 (a) A two-piece implant system in-situ. (b) The prosthetic reconstruction is screw-retained on the implant models (Zeramex XT,
Dentalpoint AG, Spreitenbach, Switzerland).

Fig. 12 (a) A 3Y-TZP implant that shows t-m transformation already in the as-delivered state. (b) A 3Y-TZP without a transformation zone when
delivered.

Clinical Performance of Zirconia Oral Implants

Zirconia oral implants are evaluated in clinical investigations. The scientific interest in zirconia implants is reflected among else in
the fact that many systematic reviews on this type of implant have been published (Andreiotelli et al., 2009; Vohra et al., 2015;
Haro Adanez et al., 2018; Pieralli et al., 2017; Roehling et al., 2018). The more recent reviews concluded that commercially
available implants show similar survival rates as titanium implants in short term with up to two to five years (one-year survival:
95%–98%). In addition, the marginal bone loss around zirconia oral implants is not different in comparison to titanium implants
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Zirconia Ceramics: Clinical and Biological Aspects in Dentistry 827

for the same follow-up period (0.78–0.98 mm). It is noteworthy to state that most of the primary investigations were dealing with
implants used for single crown or small bridge reconstructions. For larger reconstructions or removable prosthesis on zirconia
implants no data is available and no information can be therefore given regarding survival rates.
The data for two-piece zirconia implants are considered as insufficient to date and therefore no conclusion on their (short- and
mid-term) clinical behavior can be made.

Ce-TZP-Aluminate Pseudoplastic Ceramic Composite

Zirconia-based composites were developed to resist ageing (Reveron et al., 2017; Palmero et al., 2015). The laboratory investi-
gations that have been performed were encouraging. Also, the biological testing with primary osteoblasts has shown positive
results. Furthermore, in an animal model, it was shown that miniature implants made from one of those composites integrated
well into rat femur (Altmann et al., 2017). Additional preclinical research is necessary in order to be able to describe the
mechanical, biological and clinical behavior of such ceramic composites.

Emerging Additive Manufacturing of Zirconia Dental Ceramics

Additive manufacturing (AM) or 3D printing of dental ceramics is a relatively new class of shaping technologies in which a zirconia
part is directly generated from a digitally designed virtual 3D model by adding material layer upon layer, as opposed to subtractive
manufacturing methodologies. Digital dentistry is reported to be one of the fastest-growing sectors of the AM technologies (Van
Noort, 2012). Concerning dental materials that can be used in AM, polymers are the most studied and used ones, followed by
metals. AM of ceramics is possible but issues with suitable surface finishing, mechanical properties and dimensional accuracy persist.
However, compared to subtractive CAD/CAM machining, AM of ceramics reduces material waste and tooling stresses that are
associated with the milling of ceramics. It also allows lower production costs compared to milling, faster production of customized
dental pieces with complex details (e.g., intricate internal geometries and arbitrary angles), since they involve less manufacturing steps
(Branco et al., 2020). In most of the cases, AM of zirconia is used to obtain preliminary 3D structures in green state that are built from
mixture powders with polymeric binder materials and need to be submitted to further steps of debinding and sintering.
The production of zirconia parts adopting different AM techniques has been the main focal point of some latter studies that
investigated properties as density, porosity, surface roughness, microstructure, dimensional accuracy, morphology and mechanical
behavior. It is possible to print zirconia components with mechanical properties close to milled zirconia (flexural strength
943
1154 MPa (Scheithauer et al., 2015)), fracture toughness 3.9–6.7 MPa m1/2 (Branco et al., 2020; Scheithauer et al., 2015) and
hardness 13.9 GPa (Xing et al., 2017) and high dimensional stability (Osman et al., 2017; Xing et al., 2017). Overall, the
preliminary results show that AM fabricated zirconia can be used in dental restorations such as ultra-thin occlusal veneers, with
substantial advantages for processing (Branco et al., 2020). However, besides the surface finish, the difficulties of the debinding
process of the green part influence the consistency of the mechanical performance of 3D-printed zirconia.
Among many AM technologies available, the most promising remains to be VAT polymerization (Fig. 13), which can realize
high precision and accuracy in the ranges of ten micrometers (Ioannidis et al., 2020). VAT polymerization utilizes photo-
polymerization of a ceramic slurry to produce dense objects in a layer-by-layer fashion. Typical composition of ceramic suspension
includes a monomer, photoinitiator, dispersants and solid ceramic loading of 40%–60% volume. As-printed green compacts are
manufactured with a packing density of 55% theoretical density (TD), and it is possible to achieve densities exceeding 99% TD
after sintering. The only restriction is imposed by the lengthy debinding step, that is diffusion-limited, thus depending on the
thickness of the fabricated part. However, 3D printed zirconia may be regarded as a forthcoming material for the production of
dental restorations.

Fig. 13 3D-printed by VAT polymerization occlusal veneer before removing the support structures resulting from the printing process, viewing
(from left to right) from occlusal, inner surface, and after having removed the supporting structure. Reproduced from (a) Ioannidis, A., Bomze, D.,
Hämmerle, C.H.F., et al., 2020. Load-bearing capacity of CAD/CAM 3D-printed zirconia, CAD/CAM milled zirconia, and heat-pressed lithium
disilicate ultra-thin occlusal veneers on molars. Dent. Mater. 36, e109–e116. doi:10.1016/j.dental.2020.01.016, Copyright Elsevier.
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828 Zirconia Ceramics: Clinical and Biological Aspects in Dentistry

The Outlook of Zirconia Ceramics for Dentistry

Dentistry has since the last decade been undertaking a major change of the workflow from the traditional manual dependent to
novel digital technology, where zirconia, especially the full-contour monolithic variant, has proved the ability to realize complete
digital workflow. Successful digitalization, however, requires immediate addressing of several issues; (1) the development of
digital manufacturing technologies beyond the state-of-the-art for the fabrication of net-shape zirconia FPDs. Preferably, with no
or only scarce manual work involved not having any decisive role in the determination of the final quality of the fabricated FPD.
With this restriction in mind, AM technologies appear to take over the subtractive type of manufacturing processes. (2) Over-
coming big challenge of realization of the optical appearance of the natural teeth; as optical appearance is generated by many
physical properties, such as color, translucency, opalescence and surface roughness. (3) The “bioactivation” of an otherwise bio-
inert zirconia surface for oral implantology, where hierarchical, multiscale surface texturing has emerged as a promising strategy for
enhanced soft and hard tissue integration. Other issues, such as improving mechanical reliability, chemical stability, optical
translucency and bonding strength with teeth, all have already been successfully addressed, still, an endless journey of additional
optimization is to be expected to further optimize zirconia's clinical and biological experience.

Conclusions

The large research of the 3Y-TZP's low-temperature degradation (LTD) process initiated at the onset of the present millennium was
followed by the development of new generations of zirconia ceramics systems to address the demanding needs of advanced dental
materials. Zirconia dental ceramics had ever since emerged from the oblivion masked by the dramatic failure of femoral heads to
become a dental ceramics of choice in modern restorative dentistry. Nowadays it is expanding clinical indications of tooth-colored,
metal-free all-ceramic systems from crowns and bridges, orthodontic brackets, root posts and even implants, but also allowing the
minimally invasive dentistry.
The evolution from veneer-overlayed zirconia FPDs to full contour monolithic restorations has increased the need for more
translucent and LTD resistant zirconia ceramics. The transition to yttria, fully-stabilised zirconias` however need to carefully
balance between the conflicting demands of the increasing the translucency (and LTD resistance) at the expense of losing beneficial
mechanical properties at the absence of t-m transformation mechanism depending on the perceived clinical indication.
The advent of additive manufacturing of dental ceramics has very high expectations. Still there are issues to be resolved before
the wasteful but very effective FPDs fabrication by CAD/CAM technology can be replaced. Yet the idea of the possibility to
fabricate hybrid multilayered zirconia FPDs in restorative dentistry, where the core layer would be composed of a tougher more
opaque zirconia variant to provide mechanical integrity, while the outer layer from highly translucent one for the increased
esthetics in the region of incisive to mimic dentin and enamel, respectively, is now firmly placed on the horizon.

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