767886

research-article2018
BTR0010.1177/1179061X18767886Bone and Tissue Regeneration InsightsTosiriwatanapong and Singhatanadgit

Zirconia-Based Biomaterials for Hard Tissue Bone and Tissue Regeneration Insights
Volume 9: 1–9

Reconstruction © The Author(s) 2018

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Terawat Tosiriwatanapong and Weerachai Singhatanadgit DOI: 10.1177/1179061X18767886
https://doi.org/10.1177/1179061X18767886

Faculty of Dentistry, Thammasat University, Rangsit, Thailand.

ABSTRACT: Implantable biomaterials are increasingly important in the practice of modern medicine, including fixative, replacement, and
regeneration therapies, for reconstruction of hard tissues in patients with pathologic osseous and dental conditions. A number of newly
developed advanced biomaterials have been introduced as promising candidates for tissue reconstruction. Among these, zirconia-based
biomaterials have gained attention as a biomaterial for hard tissue reconstruction due to superior mechanical properties and good chemical and
biological compatibilities. This review summarizes the types of zirconia, advantages of zirconia-based biomaterials for hard tissue reconstruction
including bone and dental tissues, responses of tissue and cells to zirconia, and surface modifications for enhanced bioactivity of zirconia.
Current and future applications of zirconia-based biomaterials for bone and dental reconstruction, ie, medical implanted devices, dental
prostheses, and biocompatible osteogenic scaffolds, are also discussed.

Keywords: Zirconia, biomaterial, reconstruction, hard tissue, medical devices, dental prostheses

RECEIVED: September 1, 2017. ACCEPTED: March 4, 2018. Declaration Of Conflicting Interests: The author(s) declared no potential
conflicts of interest with respect to the research, authorship, and/or publication of this
Type: Review article.

Funding: The author(s) received no financial support for the research, authorship, and/or CORRESPONDING AUTHOR: Weerachai Singhatanadgit, Faculty of Dentistry,
publication of this article. Thammasat University, 99 Moo 18 Paholyothin Road, Klong Luang, Rangsit 12121,
Pathumthani, Thailand. Email: s-wrch@tu.ac.th

Introduction
Pathologic conditions of hard tissues require fixative and
replacement reconstruction therapies involving the use of med-
ical implanted appliances, femoral head implants, and bone
screws1,2 as well as the application of dental prostheses, such as
dental crowns and root-formed dental implants. During the
past several years, a number of materials, such as metals, ceram-
ics, polymers, and their composites, have been used for the fab-
rication of these medical devices. Criteria such as an acceptable
mechanical behavior and biocompatible chemical composition
to avoid adverse tissue reactions have been used to define an
ideal implanted material for medical and dental applications.
A wide range of biocompatible materials have been used in
patients. Different biomedical applications require different
properties of materials, including physical, mechanical, chemi-
cal, and biochemical properties. Among these, ceramics have
been used widespread for medical device fabrication. The most
commonly used ceramics are hydroxyapatite (HA) and trical-
cium phosphate. They exhibit excellent biocompatibility due to
their chemical and structural similarity to the mineral phase of
native human hard tissues, ie, bone, tooth enamel, and dentine.
However, their clinical applications are limited because of their
brittleness and difficulty of shaping for implantation. Among
biocompatible ceramics, zirconia-based biomaterials have
gained attention as a biomaterial for reconstruction of hard tis-
sues due to their superior mechanical properties and good
chemical and biological compatibilities. Exploration into zir-
conia as a biomaterial began in the 1960s,3 with most of the
work over the years focused on the use of zirconia in orthope-
dics, specifically in the area of femoral heads for total hip
replacements.4,5 This review focuses on the types of zirconia,
advantages of zirconia-based biomaterials for bone and dental
tissue reconstruction, responses of tissue and cells to zirconia,
and surface modification methods for enhanced bioactivity of
zirconia-based biomaterials. Current and future applications of
zirconia-based biomaterials for hard tissue reconstruction, ie,
osteogenic scaffolds and medical/dental implants, are also
discussed.
Zirconia-Based Biomaterials
Zirconia has recently become one of the most popular ceramic
materials in health care practices due to its improved mechani-
cal properties, high biocompatibility, and aesthetics.6 Zirconia
is a compound consisting of 2 elements, ie, zirconium (Zr) and
oxygen (O) in dioxide form. Zirconium is a transition metal
element with atomic number of 40, atomic weight of 91.22,
and density of 6.49 g/cm3. Pure zirconium can be found in both
crystalline and amorphous forms. In nature, zirconium does
not occur in a pure state but can be found in crystalline dioxide
form (ZrO2) in minerals baddeleyite and zircon or conjugated
with silicon oxides (ZrO2 XSiO2).7–10
Pure zirconia exhibits a phenomenon called “allotropy”
which possesses different crystallographic phases due to altered
atomic arrangement. Theses phases include monoclinic (M)
phase, a deformed prism with parallel sides; tetragonal (T)
phase, a straight rectangle prism; and cubic (C) phase, a square
side straight prism. These dissimilar crystal structures are
determined by the temperature. The monoclinic phase, which
is stable at room temperature up to 1170°C, has inferior
strength; the tetragonal phase is stable between 1170°C and
2370°C with superior mechanical properties; above 2370°C,
the cubic phase is stable; and the material starts to melt at
2680°C.11–14 Zirconia phase transformation is martensitic

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2 Bone and Tissue Regeneration Insights 
transformation which is athermal, diffusionless, and associated
with the shift in lattice position less than interatomic distance.
The transformation results in volumetric change which is
about 2% to 3% in case of the cubic to tetragonal phase trans-
formation and approximately 3% to 5% for the tetragonal to
monoclinic phase transformation.10
Phase Transformation of Zirconia
As mentioned earlier, pure zirconia can be found in 3 crystal-
lographic forms depending on the temperature: monoclinic—
at room temperature, up to 1170°C; tetragonal—at temperature
between 1170°C and 2370°C; and cubic—above 2370°C to
2680°C which is its melting point. On cooling, the tetragonal
phase transforms to the monoclinic phase along with a sub-
stantial 3% to 5% increase in volume, resulting in residual stress
and cracks which sufficiently lead to catastrophic failure. This
transformation begins at 950°C and is reversible.8,15,16
Zirconia is considered to be a “ceramic steel,” which was
first described by Garvie et al17 after they found the phenom-
enon called “phase transformation toughening” in the calcia-
stabilized zirconia. The rationale behind this phenomenon was
first to stabilize the tetragonal phase of zirconia after sintering
by additional dopants or stabilizing oxide agents (eg, CaO,
MgO, and Y2O3). Sintered bodies of the tetragonal phase zir-
conia can be retained down to room temperature even though
the equilibrium phase is monoclinic. Pure zirconia alloying
with lower valance oxides results in an increase in more tetrag-
onal and cubic phases and a decrease in the amount of the
monoclinic phase at room temperature. These stabilized cubic
and tetragonal phases have the same lattice structure as in the
pure zirconia but have dopant ions substituted on Zr4+corners,
with an oxygen vacancy sites to maintain the charge neutrality.
However, the tetragonal phase remains metastable and can
then transform to the more stable monoclinic phase under
externally applied stress. The volumetric change will act in the
opposite direction against the crack propagation, resulting in
an improvement in strength and fracture toughness which
exceeds the strongest alumina ceramic at that period.8,18
Transformation Toughening and Aging
Two major properties that affect lifetime of the zirconia include
resistance to crack propagation (by the effect of transformation
toughening) and hydrothermal aging (low-temperature degra-
dation [LTD]). Phase transformation toughening, which
improves zirconia mechanical properties, can be achieved when
the tetragonal phase is metastable. In other words, tetragonal
grains are able to transform under stress to stable monoclinic
grains. However, without stress, this metastable tetragonal phase
at the material surface can transform with water or humidity
contact, such as body fluids. This phenomenon was first described
by Kobayashi et al19 and is known as “aging” or “LTD.” It has
been reported that 3% mol yttrium-doped tetragonal zirconia
polycrystal (3Y-TZP) femoral heads processed under autoclave
sterilization fail after 1 to 2 years in vivo.20
Both phase transformation toughening and aging occur
together. This is like a 2-sided sword: the positive side is the
stress-induced transformation to enhance mechanical proper-
ties, whereas the negative side is that the surface transforma-
tion introduces grain pull up, roughening surface, and initiating
cracks.21 Processing zirconia ceramics that are able to trans-
form under stresses but with the resistance to aging with water
is at stake. It becomes quite clear that the Y-TZP for orthope-
dics might not have been an option.20
Type of Zirconia
Zirconia can be categorized into 3 main types, depending on
dopants and its concentration, and the temperature of
processing17:
1. Partially stabilized zirconia (PSZ) ceramics;
2. Tetragonal zirconia polycrystals (TZPs);
3. Zirconia-dispersed ceramics.
Zirconia dopants
Dopants or metal oxides used for stabilizing the tetragonal or
cubic phases of zirconia can be classified according to the
valence of cation and solubility in zirconia lattice. Commonly
used divalent cations are calcium and magnesium, which pos-
sess low solubility. These dopants generally form tetragonal
grains in the cubic matrix called PSZ.10,21 In PSZ, there is no
more phase transformation toughening due to transformed
tetragonal after cooling. Yttrium is the most used trivalent cat-
ion, and in certain applications, scandium, gadolinium, gallium,
and iron can also be used. These trivalent cations give rise to
either TZPs or PSZ ceramics depending on the processing and
temperature. Tetravalent dopants such as cerium and titanium
have the high solubility and stabilize tetragonal phase to form
TZP ceramics. These tetravalent dopants improve the aging
resistance but impair mechanical properties due to higher
phase stability.21
Decreasing “oxygen overcrowding” around zirconium cations
through the introduction of oxygen vacancies,22 which is the
weak spot of the lattice, or through the expansion of the cation
lattices, is how most stabilizers work. One of the major difficul-
ties in processing and using zirconia ceramics is maintaining the
delicate balance between the tetragonal phase stability necessary
to prevent aging and the tetragonal phase transformability nec-
essary for phase transformation toughening. The tetragonal
phase can be stabilized at room temperature but is readily trans-
formable under applied stress, whereas the absence of oxygen
vacancies will prevent the occurrence of aging.
PSZ ceramics
In 1975, calcia-stabilized (Ca-doped) zirconia was claimed to
be the first material in the history to have phase transformation
toughening.17 Then, magnesia-stabilized (Mg-doped) zirconia
Tosiriwatanapong and Singhatanadgit 3
Figure 1.  Scanning electron micrographs of 3% mol yttria-doped tetragonal zirconia polycrystal grain at different magnification: (A) ×10 000 and
(B) ×20 000.
was started to be used in orthopedics. In PSZ, tetragonal or
monoclinic zirconia nanometric precipitates are embedded in
cubic zirconia matrix. A high concentration of yttria (>4% mol)
can be found in PSZ form by high temperature treated and
special cooling. Partially stabilized zirconia ceramics have lower
strength compared with 3Y-TZP but considered as an alterna-
tive due to higher toughness20 and resisted to aging.23 Roy
et al24 showed that Mg-PSZ prostheses retrieved from femoral
heads do not show any sign of aging after 5 years. Mg depletion
can occur after water exposure at 200°C, resulting in tetragonal
to monoclinic transformation at the surface.25,26 In dentistry,
the yellow-orange color of Mg-PSZ also compromised the
popularity for dental crown and bridge fabrication.
Tetragonal zirconia polycrystals
Monolithic tetragonal phase is another name for TZPs. Even
though phase diagram and the sintering protocols for Y-TZP
dictate that cubic phase should be a secondary phase, in most
Y-TZP and Ce-TZP, tetragonal phase is considered the major or
only phase. The Y-TZP is of special interest, as this is used for
femoral prosthesis heads and, more recently, of dental prostheses
such as crowns and bridges. Essentially, after the original work
on PSZ, most of the practical knowledge on phase transforma-
tion toughening and on aging has been acquired on Y-TZP.24
In general, 3Y-TZP acquires combination of strength and
toughness among oxide ceramics, as a direct benefit of fine
grain size and transformation toughening (Figure 1). Despite
all these advantages, this material lacks resistance to aging.
Ce-TZP (10%-12% mol yttria-doped) also has large grain size
and inferior hardness and strength compared with those of
Y-TZP.21 In contrast, in tetravalent dopant–stabilized zirconia,
tetragonal phase is able to transform to monoclinic phase under
stress but resists to aging.
Zirconia-dispersed ceramics
These dispersion-toughened materials, such as ZrO2-toughened
alumina (Al2O3), have been termed zirconia-toughened alumina
(ZTA).21 Adding transformable zirconia tetragonal phase in a
nontransformable matrix is a possible option. Partially stabilized
zirconia ceramics may be considered as one of these composites;
the nontransformable matrix is made of cubic zirconia. The most
used matrix is alumina and tetragonal zirconia particles are
embedded in the alumina matrix. This is also called ZTA.
In such composites, the zirconia phase must be stabilized
in the tetragonal phase. Yttria and ceria are the most used
dopants/stabilizing oxides to stabilize the tetragonal phase.8
Another approach is that pure zirconia particles can be sta-
bilized within a high-stiffness alumina matrix. The compos-
ites can then be highly resisted or insensitive to aging.20 The
stability of the tetragonal phase is not easy to control: too
small tetragonal zirconia particles will not transform under
stress, resulting in impaired mechanical properties of the
composites.
Advantages of Zirconia-Based Biomaterials for Hard
Tissue Reconstruction
Improved material strength
As mentioned above, stabilization of zirconia ceramics can be
achieved by alloying pure zirconia with other dopants, and con-
sequently, the tetragonal phase can be partially stabilized at
room temperature even though the equilibrium phase is mono-
clinic. Compared with alumina ceramics, these metastable
tetragonal ceramics exhibit higher strength and exceptional
fracture toughness when the transformation toughening is
triggered by stress from crack tip. Transformation from a
tetragonal phase to a monoclinic phase is associated with 3% to
5% volume expansion, resulting in compression of crack tip,
inhibition of crack propagation, and enhancing fracture tough-
ness. The Y-TZP exhibits high flexural strength (900-
1200 MPa) and fracture toughness (9-10 MPa m0.5).27,28 In
dental tissue replacement, high-strength Y-TZP has been used
as root canal posts,29 frameworks for all-ceramic crowns and
fixed dental prostheses (FDPs),30 custom-made bars to support
fixed and removable dental prostheses,31 implant abutments,32
and dental implants.33
4 Bone and Tissue Regeneration Insights 

Figure 2.  (A-C) Scanning electron micrographs of MC3T3-E1 preosteoblasts and RAW 264.7 monocyte/macrophage cells grown on zirconia for 24 hours.
A and D show micrographs at low magnification, whereas B, C, and E show micrographs at higher magnification. Note that well-spreading cells with
cytoplasmic projections, resembling filopodia are shown in B and E, and dividing cells are presented in C, suggestive of a highly cytocompatible surface.

Enhanced aesthetic recipient or beneficiary of that therapy, but generating the most
appropriate beneficial cellular or tissue response in that specific
During dental restoration, especially in an anterior maxilla region,
situation, and optimizing the clinically relevant performance of
the color of tooth being replaced is a critical issue. The Y-TZP, that
that therapy.39
has superior optical property compared with that of metallic
Zirconia is considered as a biocompatible material, and no
framework, is used very popularly in dental restoration, but it is
cytotoxic effect for zirconia ceramic has been shown in sev-
still too white and opaque. Because the aesthetic demand of
eral cell types when tested both in vitro and in vivo.27,40 It has
patients requiring a ceramic restoration is to be harmonized with
been reported that several ceramics including zirconia show
the adjacent natural teeth, the translucency is one of the key for
no cytotoxicity to gingival fibroblasts.41 Josset et al42 investi-
successful factors for dental restorations. Zirconia-based ceramics
gated human osteoblast behavior in culture with zirconia
have poor translucency according to the amount of crystalline
discs, and they found that the osteoblasts showed good adhe-
density, chemical nature, and the sintered density which determine
sion and spreading properties and the cells preserved their
the amount of transmitted, reflected, and absorbed light. Most of
capacity to proliferate and differentiate into osteogenic path-
the light passing through it is intensely scattered and diffusely
ways. The scanning electron microscopic results from our
reflected, leading to its opaque appearance.34 Some studies sug-
laboratory also support the cytocompatibility of zirconia for
gested that light transmission could be enhanced by microcrystals
preosteoblasts and monocyte/macrophage cells (Figure 2).
and full densification.35,36 Jiang et al37 found that Y-TZP could
Scarano et  al43 examined the bond response to zirconia
gain nearly full density and high transmittance if sintering tem-
implants inserted into tibia of rabbits when the implants were
perature is 1450°C to 1500°C. Coloring agents were also intro-
retrieved after 4 weeks. They reported an evidence of new
duced to mimic natural color of teeth by adding coloring oxides to
bone formation and osteoblasts directly on zirconia implants
zirconia powder before or after sintering. Color can be customized
with no observable inflammatory responses.43 Biocompatibility
involving infiltration of the machined restoration at the presinter-
of zirconia may be attributed to good hydrophilicity and pro-
ing porous stage to produce work pieces of various shades.38
tein adsorption. It has been shown that albumin, a cell adhe-
sion–inhibiting protein, is adsorbed more quickly than
High biocompatibility
fibronectin, a cell adhesive protein, onto titanium. Moreover,
Biocompatibility refers to the ability of a biomaterial to per- albumin adsorption rate to titanium was more rapid than that
form its desired function with respect to a medical therapy, to zirconia. This supports the notion that zirconia is highly
without eliciting any undesirable local or systemic effects in the biocompatible and is at least comparable with titanium.44
Tosiriwatanapong and Singhatanadgit 5
It has been suggested that zirconia is unlikely to generate
mutations of the cellular genome.45 In particular, mutant fibro-
blasts found on zirconia were fewer than those obtained with
the lowest possible oncogenic dose compatible with survival of
the cells.46 Moreover, zirconia causes less phlogistic reaction in
tissue than other restorative materials, such as titanium.47 This
result is also supported by a study on peri-implant soft tissue
around zirconia healing caps compared with that around tita-
nium healing caps. Inflammatory cell infiltration, microvessel
density, and the expression of vascular endothelial growth fac-
tor were found to be higher around the titanium caps than
around the zirconia caps.48
Less bacteria adhesion
Bacterial accumulation is known to correlate with extensive bone
loss around implanted biomaterials. Bacterial adhesion shows a
direct positive correlation with surface roughness. Other surface
characteristics also seem to be of importance regarding bacterial
biofilm formation. Different bacterial adhesion affinities have
been reported for different biomaterials. Surface wettability and
roughness may influence the adhesion of bacteria on biomateri-
als. Bacteria adhesion also depends on the bacterial species and
biomaterial surface properties. For example, while hydrophilicity
is the predominant factor for Staphylococcus epidermidis, surface
topography appears to be the key predominant factor for
Streptococcus sanguinis.49 Moreover, zirconia showed significantly
more adherent Streptococcus mutans, cariogenic bacteria, than did
titanium, whereas S sanguinis seemed to adhere easily to Ti spec-
imens. No differences were noted for Actinomyces spp and
Porphyromonas gingivalis.50 Scarano et al51 found a degree of bac-
teria coverage of 12% on zirconia as compared with 19% on tita-
nium. However, it has also been reported that the adherence of
the periodontopathic bacteria on zirconia was similar to that on
titanium.52 Candida albicans was hardly observed on zirconia
samples. It has been demonstrated that zirconia accumulated less
bacteria in vivo than titanium in terms of the total number of
bacteria and the presence of potential pathogens. Although sev-
eral lines of evidence support the advantage of zirconia, in atten-
uate bacterial adhesion, over the titanium surface, a recent study
by Wassmann et al49 suggested that zirconia did not show any
lower bacterial colonization potential than titanium. It is impor-
tant to note that biomaterial surface properties and species of
bacteria of interest are key factors influencing the accumulation
of bacterial biofilms. Specific types of bacteria studied should
also be appropriately selected based on the nature of biomaterial
application and the commonly exposed species of bacteria.
Enhancement of bioactivity of zirconia by surface
modification
Following placement of a biocompatible material, including
zirconia, in the body, the tissue responds to the implanted
material surface by allowing water molecules to interact with
the surface53 and subsequently forming an adsorbed protein
layer.53,54 This allows cellular adhesion, migration, and differ-
entiation, which occurs from a few hours to several days after
implantation.55 It is noteworthy that the cell-protein–bound
surface interface occurring from as short as minutes after and
up to days following biomaterial placement is of paramount
importance for successful bone regeneration. This stage is
tightly regulated by a wide range of biological factors, includ-
ing extracellular matrix proteins, cell surface–bound, and
cytoskeletal proteins, by chemical characteristics and topogra-
phies at the biomaterial surface, and by the released ions/prod-
ucts from the grafted material.56 The ongoing development of
surface modification methods of biomaterials for bone recon-
struction, including zirconia, is therefore aimed to minimize
such effects as well as to promote rapid wound healing and
osseointegration of the grafted material.
A number of approaches have been considered in an attempt
to achieve rapid and long-term success of osseointegrated zir-
conia-based biomaterials. Surface modification of either
topography or chemistry, such as particle blasting, acid etching,
oxygen plasma, UV treatment, and a combination of these
treatments, greatly influences the surface bioactivity of zirco-
nia. These include surface hydrophilicity, protein adsorption,
osteoconduction (such as cellular attachment, spreading, and
proliferation), and osteoinduction (such as osteogenic differen-
tiation and mineralization). A recent study on the effect of acid
etching reported that rough zirconia surface could effectively
be prepared by acid etching pretreatment following glass infil-
tration and the resulting zirconia surface showed considerably
enhanced favorable osteoblast responses.57 In addition, when
compared with the well-accepted biomaterial titanium surface,
modified zirconia mediates a prominently stronger effect on
the adhesion, proliferation, and differentiation in osteoblastic
cells.58 Influence of microstructured yttria-stabilized zirconia
with surface modification by sandblasting, acid etching, heat
treatment, and combinations on primary human osteoblast
responses was also reported by Bergemann and colleagues
(2015)59. Their results suggest that the yttria-stabilized zirco-
nia possessing certain topographically modified surface show
promising biological responses. Micro- and nanotopographies
on zirconia by alumina blasting and hydrofluoric acid etching
have been suggested to be a promising surface of enhancing
favorable responses of osteogenic cells.60 Noro et al61 investi-
gated surface characteristics and bioactivity of zirconia with
modified surface topography (produced by alumina blasting
and acid etching with hydrofluoric acid) and modified surface
physicochemistry (modified with oxygen plasma, UV light, and
hydrogen peroxide treatment), and the results showed that
modification of surface topography or physicochemistry, espe-
cially of blast/acid etching as well as oxygen plasma and UV
treatment, significantly augmented the surface hydrophilicity,
resulting in superhydrophilicity. A notable reduction in carbon
content and the substitution of hydroxyl groups may contribute
6 Bone and Tissue Regeneration Insights 
to the reported superhydrophilicity. The resulting enhanced
hydrophilicity of the modified zirconia is also sustainable, even
with an aqueous solution storage following surface modifica-
tion, a key consideration in translating into clinical applica-
tion.61 Wu et  al modified the surface of zirconia using an
oxygen plasma treatment which resulted in an enhanced and
stable wettability zirconia surface. Such improved wettability of
zirconia has also been shown to promote the attachment, pro-
liferation, and osteogenic differentiation of human osteoblast-
like cells.62 Moreover, modification of biomaterial surface by
osteogenic short-peptide immobilization has been suggested to
enhance osteoconduction and osteoinduction of biomaterials
for bone regeneration.63,64 It has also been shown that immobi-
lization of a short protein peptide on the nanostructured cubic
zirconia surface is achieved with a magnitude of adsorption
energy higher than that on the atomically flat (smooth) surface.
The strong electrostatic interactions are a major contributing
factor in the enhanced adsorption immobilization at the nano-
structured surface. It has been reported that the best electro-
static and steric fit of the protein to the inorganic surface
corresponds to a minimum of the adsorption energy deter-
mined by the noncovalent interactions. UV pretreatment has
also been reported to increase the bioactivity of zirconia-based
materials, in terms of cellular attachment, proliferation, and
eventually in vitro mineralization by fully active osteoblasts.65,66
This is attributed to the finding that UV treatment decreases
the amount of surface carbon and converts the hydrophilicity
status from hydrophobic to superhydrophilic.65 Taken together,
certain surface-modified zirconia-based biomaterials are likely
to be one of the materials of choice for dental/medical implants
for hard tissue reconstruction.
Current and Future Applications of Zirconia-Based
Biomaterials for Hard Tissue Reconstruction
Medical implants
Zirconia offers high fracture toughness and flexure strength
and is therefore one of the most fracture-resistant ceramics.
Zirconia has been introduced to replace alumina in orthopedic
uses with superior wear resistance because poor fracture tough-
ness of alumina results in the unfavorable release of wear parti-
cles. To resolve some disadvantages of pure zirconia (ie,
instability and phase transformation, leading to changes in
shape and volume), stabilizing materials, such as magnesia
(magnesium oxide), quicklime (calcium oxide), and yttria
(yttrium oxide), are added. Controlled phase transformation is
used to develop different zirconia composites for medical/
orthopedic applications. These include TZP ceramic, which is
the strongest and toughest zirconia-based ceramic with opti-
mal material density and fine grain size. In addition, Y-TZP
became a promising alternative structural ceramic because of
its higher fracture toughness and strength.8 Mixed composites
of ZrO2 and Al2O3, known as ZTA, are also used successfully
in hip replacement.67 Zirconia-toughened alumina is a 2-phase
biomaterial manufactured of zirconia particles dispersed in a
dense, fine-grained alumina matrix. However, ZTA is still
unstable, as it derives its strength and toughness from the
mechanism that resulted in catastrophic failure of the zirconia-
based medical materials.68 Zirconia-toughened alumina
achieve its properties through phase instability of the material
itself. However, the instability of zirconia is exacerbated by
human body temperature and moist environment. As zirconia
transforms, its strength and toughness are reduced and over
time the mechanical performance is just comparable with con-
ventional alumina. A significant amount of work is clearly
required to solve this limitation of zirconia-based materials.
Dental prostheses
Since early 1990s, zirconia has been used as substructures to
support veneering ceramic materials for dental restorations.
Most clinical failures reported in the literature69 were fractures
of veneering porcelain system with the rate of 2% to 9% for
single crowns after 2 to 3 years and 3% to 36% for multiple-unit
dental restorations after 1 to 5 years.70,71 New innovations are
focusing on improving veneering technique by alternating
manufacturing process of veneer using computer-assisted
design and computer-assisted manufacturing (CAD/CAM)
and modified sintering protocol. However, modifying veneer-
ing technique has not been very popular.72
Recently, monolithic zirconia or full-contour zirconia resto-
ration has been introduced to avoid using veneering ceramics
as an alternative way.38 The fracture resistance of monolithic
zirconia has been reported by many authors. Preis et al73 stud-
ied fracture resistance of 3-unit zirconia-based FDPs under
different conditions. The median fracture force ranged from
1173.5 to 1316.0 N without statistical differences between
groups, suggesting that full-contour zirconia FDPs might be
considered as an alternative treatment option due to their high
resistance to fracture. Zesewitz et  al74 investigated different
single monolithic all-ceramic crowns including monolithic zir-
conia crowns, monolithic lithium disilicate, and monolithic
feldspar ceramics. Monolithic zirconia crown exhibited the
highest fracture resistance of all the samples studied under
loading. The highest mean fracture load was reported as 5620 N
for zirconia crowns.
New-generation zirconia with outstanding translucency
for highly aesthetic restorations requires no porcelain veneer
buildup. Increasing yttria concentrations may result in an
increased cubic phase and an improved optical property
(Figure 3). Optical property is a major challenging issue;
composition, sintering protocol, and addition coloring liq-
uids can be used for enhancing translucency. Beuer et  al75
showed that the light transmission of the polished zirconia
full crown was significantly higher than that of glazed and
veneered zirconia. In another study, Ilie and Stawarczyk76
compared the amount of light transmission through mono-
lithic zirconia, conventional zirconia, and glass ceramics and
Tosiriwatanapong and Singhatanadgit 7
Figure 3.  Scanning electron micrographs of high yttria-doped tetragonal zirconia polycrystal grain at different magnification: (A) ×10 000 and
(B) ×20 000.
reported that the zirconia was less translucent than the con-
ventional glass ceramic and the translucency decreased with
increased thickness of materials. Although, recently, the
translucency of zirconia has been improved, it is still not
comparable with that of glass ceramics. The results from the
studies also indicate that care should be taken in selecting
the shade and polymerizing modes.
Future development of zirconia-based materials to gain
more light transmission is challenging and can enhance the
treatment result for the patients. “Aging-free” zirconia is an
ideal goal but quite difficult to achieve because the transfor-
mation occurring during aging is a “natural” return to the
monoclinic equilibrium state. One approach to avoid oxygen
vacancies introduced by yttria doping is to select proper
codopants such as tetravalent stabilizers or combined triva-
lent and pentavalent ions to minimize the vacancies required
for charge neutralization. Nowadays, there are no commer-
cially available zirconia-based materials that fulfill ideal
properties. Fully free of aging, naturally translucent and
phase-stable zirconia and its composites are options for the
next decade.
Osteogenic scaffolds for hard tissue engineering
It has recently been reported that porous zirconia scaffolds may
be fabricated by milling CAD/CAM blocks into the desired
shape, and the HA-incorporated zirconia scaffolds possessed
dramatically higher in vivo new bone formation volume.77 This
suggests that HA enhances osteogenic potency of porous zir-
conia/HA scaffolds. New bone formation can be observed at
the pore cavity walls initially, followed by deposition of the
entire pore volume. Islands of entrapped HA particles can also
be observed in mineralized bone matrix.77 Furthermore, new
porous gradient HA/zirconia biomaterials can be prepared
using foam-immersion, gradient-compound, and high-tem-
perature sintering. These scaffolds can promote bone repair
and support bone to grow into the scaffold pores.78
Zirconia/HA scaffolds with different zirconia: HA
ratios have also been fabricated, optimized, and extensively
characterized. The porosity of a zirconia/HA scaffold can be
adjusted from approximately 70% to 90%, and the compres-
sive strength of the scaffold increases from 2.5 to 13.8 MPa
when the zirconia content increased from 50 to 100 wt%.
The biological responses in terms of cell adhesion and prolif-
eration to the zirconia/HA scaffolds can be improved when
compared with those scaffolds made from zirconia alone.
Moreover, an in vivo study suggests that a stem cell–loaded
zirconia/HA scaffold enhances bone regeneration around
the implanted biomaterial.79 In addition, zirconia/HA-based
porous bioceramics loaded with recombinant human BMP-2
promote the repair of bony defect and facilitate bone growth
in vivo, which might substitute the use of iliac bone grafts in
routine clinical practice.80 Taken together, zirconia-based
scaffolds show good mechanical performances and biocom-
patibility and are promising biomaterials to be used in bone
reconstruction needed in the treatment of load-bearing large
bone defects.
Author Contributions
Conceived the concepts: TT. Contributed to the writing of the
manuscript: TT, WS. Developed the structure and arguments for the
paper: TT. Made critical revisions and approved final version: TT.
All authors reviewed and approved of the final manuscript.
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