J Mater Sci (2015) 50:4779–4812
DOI 10.1007/s10853-015-9056-3
REVIEW
Biomaterials for dental implants: current and future trends
Donatella Duraccio1 • Federico Mussano2 • Maria Giulia Faga1
Received: 19 January 2015 / Accepted: 23 April 2015 / Published online: 5 May 2015
Ó Springer Science+Business Media New York 2015
Abstract The urge to replace missing teeth dates back to
the origin of medicine. Along history, organic materials,
metals, alloys, polymers, glasses, and carbon were used to
substitute teeth, but only in the past thirty years was a truly
scientific approach implemented introducing the concept of
osseointegration. This review aims at recapitulating the
materials of choice, the surface modifications, and the most
updated research advancements in the field of oral
osseointegrated implants. As the accepted clinical standard,
commercially pure Titanium, Ti–6Al–4V and, to a lesser
extent, zirconium dioxide will be described from the per-
spective of physical, mechanical, and biological features,
together with in vitro, in vivo, and clinical assessment of
biocompatibility. Outlines of the researches that are
presently conducted in an endeavor to limit the drawbacks
of the current technology are also provided. Novel Tita-
nium alloys such as Ti–Zr and Ti–20Nb–10Zr–5Ta,
Zr61Ti2Cu25Al12, innovative production methods for non
metallic materials as well as ceramic composites will be
considered as possible promising candidates for future
dental implants
& Donatella Duraccio
d.duraccio@imamoter.cnr.it
1 [3, 4].
Institute for Agricultural and Earthmoving Machines
(IMAMOTER)-CNR, Strada delle Cacce 73, 10135 Turin,
Italy
2
Department of Surgical Sciences CIR Dental School,
University of Turin, via Nizza 230, 10126 Turin, Italy
What is a dental implant?
Introduction
The goal of modern dentistry is to restore the patient to
normal function, speech, health and esthetics, regardless to
the atrophy, disease, or injury of the stomatognathic sys-
tem. Replacing single missing teeth, especially in the an-
terior region, has always been a challenge for dentists.
With increasing patient demands, removable partial den-
tures have become less acceptable and many patients now
oppose the preparation of intact teeth for the fabrication of
a fixed partial denture.
Among various dental materials and their successful
applications, a dental implant is a good example of the
integrated system of science and technology involved in
multiple disciplines including surface chemistry and phy-
sics, biomechanics from macro-scale to nanoscale
manufacturing technologies, and surface engineering.
Dental implant materials encompass a variety of mate-
rials with different degrees of interaction with the human
body. Immediately after insertion of the implant, this
contact provides primary stability through friction and
mechanical interlocking between the implant thread sur-
face and the bone trabeculae. During the following weeks,
the peri-implant bone is remodeled and replaced by newly
formed bone [1, 2]. The major part of the final bone-im-
plant contact is thus based on newly formed bone that
originates from the adjacent peri-implant bone and is laid
down on the implant surface in an osteoconductive manner
In the past 30 years, the number of dental implant pro-
cedures has increased steadily worldwide, reaching about
one million dental implantations per year. The clinical
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success of oral implants is related to their early osseoin-
tegration [1, 5].
Geometry and surface topography are crucial for the
short- and long-term success of dental implants [6–8].
History of implants and their use in dentistry
The desire to replace missing teeth with something similar
to the root of a tooth dates back thousands of years and
includes civilizations such as ancient Chinese, Egyptians,
Greeks and Etruscans. A skull was found in Europe with a
ferrous metal tooth dated back to the time of Christ. Incas
from Central America took pieces of sea shells and similar
to the ancient Chinese tapped them into the bone to replace
missing teeth [9]. History shows then that it has always
made sense to replace a tooth with an implant in the ap-
proximate shape of a tooth.
The first prototype of the hollow cylinder implants used
today was introduced in 1906 by Greenfield [10] and was
made of an iridium-platinum alloy. In the early 1930s,
more emphasis was placed on the tissue tolerance as well
as the bone reaction toward metal implants. Strock [11]
succeeded in anchoring a Vitallium (cobalt-chromium-
molybdenum alloy screw) within bone and immediately
mounting a porcelain crown to the implant. At the same
time, Müller placed the first implant, made of an iridium-
platinum alloy into the oral cavity. From the 1950s, nu-
merous implantologists developed implant procedures [11–
14].
Modern oral implantology began when Per-Ingvar
Brånemark, a physician who was conducting experiments
in vivo using Titanium chambers placed within bone, dis-
covered the particular connection this metal was able to
develop within the recipient tissue [15]. In 1965, Bråne-
mark proposed a ‘‘bone-anchored bridge’’ to treat edentu-
lous mandibles. The concept of osseointegration was
originally proposed and developed in two fundamental
publications [1, 16]. In particular, Brånemark observed that
a piece of Titanium embedded in rabbit bone becomes
firmly anchored and difficult to remove [17]. Following
1 year of observation, no inflammation was detected in the
peri-implant bone; meanwhile, soft tissue had formed an
attachment to the metal and bone to the titanium [18]. Even
if the osseointegration was not accepted as a clinical
achievement and was regarded as impossible by many [19],
the Brånemark system of dental implants was introduced in
1971 [20]. For more details on the history of dental im-
plants, read also references [21–34].
Nowadays, the most frequently used implant material is
Titanium. As a result of Brånemark’s extensive studies,
Titanium has become the gold standard in implant den-
tistry. However, the great revolution in the field of ceramic
materials with the use of zirconium dioxide and also other
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materials has opened a new, challenging way in
implantology.
Dental implant features
A dental implant is an artificial tooth root that is placed into
jaw in order to hold a replacement tooth (the crown). The
implant emulates the shape of the root. The implant is
surgically incorporates into the bone over time to become a
stable base for crowns. Dental implants can replace a single
tooth, several teeth, or support partial or full dentures.
In Fig. 1 [35], a schematic representation of an implant
supported structure is reported. It is possible to identify
three parts: (a) the implant fixture that will be the object of
this review; (b) the abutment placed over the fixture to hold
the crown; and (c) the crown that can be cemented or
screwed to the abutment.
There are variations in the overall shape of the implant:
screw-type and cylinder-form implants. The first one is the
most used and includes ‘‘tapered root-form implants’’ and
‘‘straight (parallel-walled) implants.’’ It can be placed in
smaller sockets and transmit biting force efficiently to the
bone. The cylinder-form implant has a cylindrical shape
without screw threads and can be placed easily in the
jawbone. However, it does not show sufficient primary
stability because the surface area is smaller than that of
screw-type implants.
The establishment of a strong biomechanical bond be-
tween implant and jawbone is called osseointegration.
Brånemark described the osseointegration [1, 17] as direct
contact (at the light microscope level) between living bone
and implant. Based on histology, osseointegration is de-
fined as the direct anchorage of an implant by the formation
of bone tissue around it without the growth of fibrous tissue
at the bone–implant interface. A 100 % bone-to-implant
contact does not occur. No consensus opinion could be
arrived as to the extent of bone-to-implant contact required
for acceptance of the connection as osseointegration or on
Fig. 1 Schematic diagram of
the screw-shaped artificial tooth.
Reprinted from Ref. [35] with
permission
J Mater Sci (2015) 50:4779–4812
the criteria for definition of the term. Irrespective of all the
confusions involved in the definition, a successful
osseointegrated oral implant has to meet certain criteria
reported elsewhere [36–41].
The success of osseointegration depends on many fac-
tors including mainly medical status of the patient, smok-
ing habits, bone quality, bacterial contamination,
immediate loading, and implant surface characteristics
[40]. Success rates of 85 % or more at the end of a 5-year
observation period and 80 % at the end of a 10-year period
are the minimum criteria for implant success [37–39].
Materials used for dental implants
In the long history of dental implants, several materials
have been tested such as metals, alloys, ceramics, polymer-
based materials, glasses, and carbon [42–44]. The charac-
teristics required for the manufacturing of dental implants
are biocompatibility, biofunctionality, availability, together
with the capacity to osseointegrate, as defined in the pre-
vious paragraph. Biocompatibility refers to the interactions
between materials and the recipient tissues of the body and
is one of the most important factors involved with the
material selection [45]. Biofunctionality deals with those
mechanical and physical properties that enable the im-
planted device to perform its function under the stresses
imposed in the oral cavity. Availability refers to the
handiness of the fabrication and sterilization techniques of
the implants [45].
This review will mainly focus on pure Titanium, its
alloy Ti6Al4V and zirconium dioxide (Zirconia), owing to
their wide use and numerous favorable physical, me-
chanical, and biological features. A short section will be
dedicated to those materials the continuous research in the
field is developing, prompted by some drawbacks of the
current technology.
Ti and Ti–6Al–4V
Structure and properties
Once considered a rare metal, Titanium is nowadays one of
the most important metals in the industry, and has become
the most commonly used implant material in dentistry, as a
result of Brånemark’s studies. This element was first dis-
covered in England by Gregor in 1790, although it received
its name by Klaproth after the mythological first sons of the
earth, the Titans, only in 1795 [46]. Titanium was the ninth
most abundant element and the fourth most abundant
metallic element in the earth’s crust, following aluminum,
iron, and magnesium. Being a transition element, Titanium
has an incompletely filled d shell in its electronic structure
4781
[46]. Titanium exists in two allotropic forms. In the ele-
mental form, it has a hexagonal closed packed crystal
structure (hcp), which is commonly known as a, whereas
above about 883 °C it has a body-centered cubic structure
(bcc) termed b [47].
Titanium can be alloyed with a wide variety of ele-
ments to alter its properties, mainly for the purposes of
improving strength, high-temperature performance, creep
resistance, response to aging heat treatments, and forma-
bility [48]. The a to b transformation temperature of pure
Titanium either increases or decreases based on the nature
of the alloying elements. The alloying elements such as
(Al, O, N, C) that tend to stabilize the a phase are called
a-stabilizers and the addition of these elements increases
the b transus temperature, while elements that stabilize b
phase are known as b-stabilizers (V, Mo, Nb, Ta, Fe, Cr,
Fe, W, Si, Co, Mn, H) and addition of these elements
depresses the b transus temperature. Some of the elements
that do not have marked effect on the stability of either of
the phases, but form solid solutions with Titanium, are
termed as neutral elements (Zr and Sn). However, data
carried out by Geetha et al. [49] and Tang et al. [50] have
proven that the addition of Zr stabilizes the b phase in
Ti–Zr–Nb system.
Titanium alloys may be classified as a, near-a, a ? b,
metastable b, depending upon the room temperature mi-
crostructure [51]. Alloys having only a stabilizers and
consisting entirely of a phase are known as a alloys. Alloys
containing 1– 2 % of b stabilizers and about 5–10 % of b
phase are termed as near a alloys. Alloys containing higher
amounts of b stabilizers resulting in 10–30 % of b phase in
the microstructure are known as a ? b alloys. Alloys with
still higher b stabilizers where b phase can be retained by
fast cooling are known as metastable b alloys. These alloys
decompose to a ? b on aging. The properties of the ma-
terials depend on the composition, relative proportions of
the a and b phases, thermal treatment, and thermo-me-
chanical processing conditions. The b alloys also offer the
unique characteristic of low elastic modulus and superior
corrosion resistance [52, 53]. Dental implants are usually
made from commercially pure Titanium (cpTi) with var-
ious degrees of purity (graded from 1 to 4 in dependence of
oxygen, carbon, and iron content). Grade 4 cpTi is the most
common used as it is stronger than other grades. Com-
mercially, it is also possible to find the a ? b alloy Ti–
6Al–4V that contains 6 % aluminum and 4 % vanadium. It
is normally used in annealed condition and has greater
yield strength and fatigue properties than pure Titanium
[54].
The details of phase transformation and processing-mi-
crostructure-property relationships of Ti and Ti–6Al–4V
are thoroughly reviewed in several papers and books [50,
55–64].
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The compositions in weight percentage of commercially
pure Titanium and of the two types of Titanium alloys used
in implant dentistry, as given in several American Society
for Testing and Materials (ASTM) Standards, appear in
Table 1. Some of these materials can be supplied in the
ELI condition (Exra Low Interstitial content) (ASTM
2000).
A comparison between the mechanical properties of
cpTi and Ti–6Al–4V is made in Table 2. It is noteworthy
that, while the modulus of elasticity of cp grade 1 Titanium
to cp grade 4 Titanium ranges from 102 to 104 GPa (a
change of only 2 %), the yield strength increases from 170
to 483 MPa (a gain of 180 %).
The combination of high strength and low weight (4.5 g/
260 cm3) makes Titanium and its alloys the preferred
materials in implant dentistry [48].
A passive oxide (mainly TiO2) film protects the surface
of Titanium and its alloys. This stable and adherent passive
oxide film [62, 63] formed on the surface when they are
exposed to air, water or any electrolyte, protect surfaces
from pitting corrosion, intergranular corrosion, and crevice
corrosion attack. It is responsible for the ability to induce
osseointegration and for the excellent biocompatibility of
Ti and its alloys, although there are reports that show the
accumulation of Titanium in tissue adjacent to the implant
[64, 65].
Commonly, implants are prepared by shaping, i.e.,
subtractive material processing, through machining,
grinding, milling, and turning in the shape of a screw.
The bulk properties of Titanium (such as non-toxicity,
corrosion resistance or controlled degradability, modulus
of elasticity, and fatigue strength) have long been deemed
highly relevant in terms of the selection of the right
biomaterials for dental applications. Also, the material
surface plays an extremely important role in the response
of the biological environment to the artificial medical
devices. In implants made of Titanium, the normal
manufacturing steps usually lead to an oxidized, con-
taminated surface layer that is often stressed and plasti-
cally deformed, non-uniform, and rather poorly defined.
Such ‘‘native’’ surfaces are clearly not appropriate for
Table 1 Titanium grades 1–4 and Titanium alloys (Ti–6Al–4V) compositions from ASTM Standard (ASTM 2000)
O (wt%) C (wt%) Fe (wt%)
CpTi, grade 1 0.18 0.10 0.02
CpTi, grade 2 0.25 0.10 0.03
CpTi, grade 3 0.35 0.10 0.03
CpTi, grade 4 0.40 0.10 0.05
Ti–6Al–4V 0.20 0.08 0.30
Ti–6Al–4V (ELI) 0.13 0.08 0.10
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J Mater Sci (2015) 50:4779–4812
biomedical applications and some surface treatment must
be performed. In fact, they improve the surface properties
required by dental applications, such as wear and corro-
sion resistance, retaining the excellent bulk attributes of
Titanium and its alloys, such as relatively low modulus,
good fatigue strength, formability, and machinability.
Moreover, numerous reports demonstrate that the surface
modification of Titanium implants affects the rate of
osseointegration and biomechanical fixation [66, 67].
Surface modifications encompass a large variety of ap-
proaches some of which are already used in clinical
practice, while others are currently being evaluated on a
preclinical level. In this review, surface modifications are
divided into two main groups: ‘‘surface roughening,’’ if
the modification concerns the surface morphology, and
‘‘surface coating,’’ if the modification concerns also the
surface composition. In Table 3, reported at the end of
‘‘Titanium surface coating’’ section, the advantages and
disadvantages of the different surface modifications are
summarized.
Titanium surface roughening
There are a number of Titanium surfaces commercially
available for dental implants. Most of these surfaces have
proven clinical efficacy. However, the development of
these surfaces has been empirical requiring no standardized
tests. Furthermore, comparative clinical studies with dif-
ferent implant surfaces are rarely performed. The exact role
of surface chemistry and topography on the early events of
the osseointegration remains poorly understood [8].
Surface roughness can be divided into three levels de-
pending on the scale of the features: macro-, micro-, and
nano-sized topologies. Various methods have been devel-
oped in order to create a rough surface and improve the
osseointegration of Titanium dental implants. The most
common used are: Titanium plasma spraying, blasting with
ceramic particles, acid etching, and anodization [8].
Titanium plasma spraying (TPS) consists in injecting
Titanium powders into a plasma torch at high temperature.
The Titanium particles are projected onto the surface of the
H (wt%) N (wt%) Al (wt%) V (wt%) Ti (wt%)
0.015 0.03 – – Balance
0.015 0.03 – – Balance
0.015 0.03 – – Balance
0.015 0.03 – – Balance
0.015 0.05 5.50–6.75 3.50–4.50 Balance
0.012 0.05 5.50–6.50 3.50–4.50 Balance
J Mater Sci (2015) 50:4779–4812 4783

Table 2 Mechanical properties of pure Titanium and of its alloys [44]; ASTM 2000
Elastic modulus (MPa) Yield strength (MPa) Tensile strength (MPa) Elongation (%)

CpTi, Grade 1 102 170 240 24

CpTi, Grade 2 102 275 345 20
CpTi, Grade 3 102 380 450 18
CpTi, Grade 4 104 483 550 15
Ti–6Al–4V 113 860 930 10
Ti–6Al–4V (ELI) 113 795 860 10

Table 3 Main advantages and disadvantages of cpTi and Ti6Al4V surface modifications
Surface treatment Advantages Disadvantages

Roughening
Plasma spraying Mechanical anchorage and fixation to bone are favored [68] Titanium wear particles in the bone [69]
Grit blasting Mechanical anchorage and fixation to bone are favored [68, 84], high Residue of blasting material interfered with
survival rate [80–83] osseointegration [69]
Etching Protein adsorbtion, osteoblastic cell adhesion, and rate of bone tissue Reduction in mechanical properties of
healing in the peri-implant region [6] Titanium [99–102]
Anodization Protein adsorbtion, osteoblastic cell adhesion, and rate of bone tissue Process rather complex [114–117]
healing in the peri-implant region [6]
Grit-blasted and acid- Accelerated bone formation in early stages of peri-implant bone Possible surface contamination with
treated surface regeneration and enhanced bone-implant contact in areas of surfaces hydrocarbons [115]
(SLA) previously not covered by bone [119–122]
2-step treatment Accelerated bone tissue regeneration and increased mechanical retention Multistep process and high temperature
[134] [134]
Coating
Plasma-sprayed HA High integration rate, fast bone attachment, direct bone bonding, [144– Coating delamination [140–143].
coating 146] high initial rate of osseointegration [138] Controversies regarding long-term
prognosis [148]
Ion implantation High percentage BIC values [161], Process extremely controllable. Expensive process, no clinical studies [157]
Possibility to have ultra-high-purity layers [157]

implants where they condense and fuse together, forming a
film about 30-lm thick. The thickness must reach
30–50 lm to be uniform. The resulting coating has an
average roughness of around 7 lm, which increases the
surface area of the implant. It has been shown that this
three-dimensional topography increased the tensile strength
at the bone/implant interface [68]. However, particles of
Titanium have sometimes been found in the bone adjacent
to implants [69]. The presence of metallic wear particles
from endosseous implants in the liver, spleen, small ag-
gregates of macrophages, and even in the para-aortic lymph
nodes has also been reported [69]. Metal ions released from
implants may be the product of dissolution, fretting, and
wear, and may be a source of concern due to their poten-
tially harmful local and systemic carcinogenic effects [70,
71]. However, the local and systemic adverse effects of the
release of Titanium ions have not been universally
recognized.
Nowadays, there is a consensus on the clinical advan-
tages of implanting moderately rough-surfaced implants
rather than using rough plasma-sprayed implant surfaces
[68, 72].
Another approach for roughening the Titanium surface
consists in blasting (also called grit-blasting or sand-
blasting) the implants with hard ceramic particles. The
highly roughened implants have been shown to favor me-
chanical anchorage and primary fixation to bone. The
abrasive ceramic particles are projected against the target
material under high pressure. Thus, for the blasting of
biomedical materials, the particles should be chemically
stable, biocompatible, and should not hamper the
osseointegration of the Titanium implants. Usually, Alu-
mina (Al2O3), Titania (TiO2), or hydroxyapatite particles
are applied for blasting treatments. The desired roughness
can be set up by the particle size. Alumina is frequently
used as a blasting material and produces surface roughness

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varying with the granulometry of the blasting media [73,
74]. However, the blasting material is often embedded into
the implant surface and residue remains even after ultra-
sonic cleaning, acid passivation, and sterilization. Alumina
is insoluble in acid and is thus hard to remove from the
Titanium surface. In some cases, these particles have been
released into the surrounding tissues and have interfered
with the osseointegration of the implants. Moreover, this
chemical heterogeneity of the implant surface may de-
crease the excellent corrosion resistance of Titanium in a
physiological environment [75, 76].
Titanium oxide is also used for blasting Titanium dental
implants. An experimental study using microimplants in
humans has shown a significant improvement for bone-to-
implant contact (BIC) for the TiO2 blasted in comparison
with machined surface implants [77]. Other experimental
studies confirmed the increase in BIC for Titanium-blasted
surfaces [78, 79]. Furthermore, some authors have reported
high clinical success rates for Titanium-blasted implants,
up to 10 years after implantation [80, 81]. Comparative
clinical studies gave higher marginal bone levels and sur-
vival rates for TiO2-blasted implants than for turned im-
plants [82, 83].
Other studies have shown that the torque force increased
with the surface roughness of the implants while compa-
rable values in bone apposition were observed [84], thus
corroborating that roughening increases the mechanical
fixation of Titanium dental implants to bone.
A third possibility for roughening Titanium dental im-
plants consists in using a biocompatible, osteoconductive,
and resorbable blasting material. Calcium phosphates such
as hydroxyapatite, b-tricalcium phosphate, and mixtures
have been considered useful blasting materials. These
materials are resorbable, leading to a clean, textured, pure
Titanium surface. Experimental studies have demonstrated
a higher bone-to-implant contact with these surfaces, when
compared to machined surfaces [85, 86] and a BIC contact
similar to that observed with other blasting surfaces when
osseointegration is achieved [87].
Sub-micro and nano-porous surfaces, preferred to highly
roughened one, can be produced by Etching and Anodiza-
tion. These surfaces promote protein adsorbtion, os-
teoblastic cell adhesion, and the rate of bone tissue healing
in the peri-implant region [88, 89].
Etching with strong acids such as HCl, H2SO4, HNO3,
and HF is another method for roughening Titanium dental
implants. Acid etching produces micro-pits on Titanium
surfaces with sizes ranging from 0.5 to 2 lm in diameter
[90, 91]. Acid etching has been shown to greatly enhance
osseointegration [92]. Immersion of Titanium implants for
several minutes in a mixture of concentrated HCl and
H2SO4 heated above 100 °C (dual acid etching) is em-
ployed to produce a micro-rough surface. It has been found
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that dual acid-etched surfaces enhance the osteoconductive
process through the attachment of fibrin and osteogenic
cells, resulting in bone formation directly on the surface of
the implant [93–96].
Another approach involves treating Titanium dental
implants in fluoride solutions. Titanium is very reactive to
fluoride ions, forming soluble TiF4 species. This chemical
treatment of Titanium created both a surface roughness and
fluoride incorporation favorable to the osseointegration of
dental implants [97, 98]. It has been shown that this che-
mical surface treatment enhanced osteoblastic differen-
tiation in comparison with control samples [99].
Fluoridated rough implants also withstood greater push-out
forces and showed a significantly higher torque removal
than the control implants [97, 98]. Nevertheless, chemical
treatments might reduce the mechanical properties of Ti-
tanium. For instance, acid etching can lead to hydrogen
embrittlement of the Titanium, creating micro cracks on its
surface that could reduce the fatigue resistance of the im-
plants [100, 101].
Indeed, experimental studies have reported the ab-
sorption of hydrogen by Titanium in a biological envi-
ronment. The hydrogen embrittlement of Titanium is also
associated with the formation of a brittle hybrid phase,
leading to a reduction in the ductility of the Titanium.
This phenomenon is related to the occurrence of fracture
mechanisms in dental implants [100–103]. The type of
acid, concentration of the solution, temperature, and time,
which also leads to different surfaces [104], are consid-
ered influencing factors, but they vary in different papers.
Lin et al. [103], for example, prepared different surfaces
by changing the etching temperature and time. They
suggested that higher temperature and shorter time of
etching are an effective way to get a uniform surface and
decrease the diffusion of hydrogen to prevent hydrogen
embrittlement.
The properties of acid-etched cpTi surfaces have been
compared with those of machined and blasted Titanium.
Characterizations included roughness, wettability, surface
free energy, X-ray diffractometry, protein adsorption, os-
teoblast adhesion and differentiation, corrosion resistance,
bioactive potential by in vitro growing in simulated body
fluid, and structural integrity of hydroxyapatite coatings
[105–110].
Most commonly, acid treatments are carried out after a
blasting step to remove blasting damaged surface zones
and to refine at the same time surface roughness charac-
teristics. More aggressive mixtures lead to generally finer
surface defect distributions, whereas less aggressive acidic
solutions induce a finer roughening [111]. After blasting,
the reactivity of surfaces against the etching solutions is
different, and thus remarkable differences in roughness
values can be achieved.
J Mater Sci (2015) 50:4779–4812
SLA surfaces (sand blasted with large grit and acid
etched) have been reported to show topographies of dif-
ferent scales at the same surface. In several investigations,
the superior quality of such a combined blasting and acid-
etching structuring technique has been demonstrated
in vitro and in vivo [112–114].
As Titanium oxide is very reactive, it is immediately
covered with a thin coating of hydrocarbons (a few
nanometers thick) when exposed to air. This process is
associated with a decrease in surface energy leading to an
increase in the water wetting angle and a more hy-
drophobic surface [115]. Hydrophobic interactions be-
tween this material surface and the proteins itself go
along with stronger interacting forces between the implant
surface and the adsorbed protein facilitating critical con-
formational changes of the adsorbed molecule. This may
result in immunological reactions or decreased functional
activity of the respective protein. Recent modifications of
SLA surfaces, thus, have been directed toward further
enhancement of early bone reactions by avoiding surface
contamination with hydrocarbons and have prompted the
development of a modified blasted and acid-etched sur-
face. Immediately after blasting and etching, the implants
are rinsed under N2 protection and stored continuously in
isotonic saline solution. This has resulted in substantially
enhanced wettability with significantly reduced contact
angles [116]. In vitro, this ‘‘ultra-hydrophilic’’ surface has
been associated with increased adsorption of fibronectin
and elevated levels of osteocalcin production when seeded
with osteoblasts [117]. Qu and colleagues have found
enhanced cluster formation and increased expression of
key osteogenic regulatory genes in osteoblasts [118].
Preclinical testing of this type of surface modification has
resulted in accelerated bone formation in early stages of
peri-implant bone regeneration and enhanced bone-im-
plant contact in areas of surfaces previously not covered
by bone [119–122].
Micro- or nano-porous surfaces may also be produced
by potentiostatic or galvanostatic anodization of Titanium
in strong acids (H2SO4, H3PO4, HNO3, HF) at high current
density (200A/m2) or potential (100 V). The result of the
anodization is to thicken the oxide layer to more than
1000 nm on Titanium. When strong acids are used in an
electrolyte solution, the oxide layer will be dissolved along
current convection lines and thickened in other regions.
The dissolution of the oxide layer along the current con-
vection lines creates micro- or nano-pores on the Titanium
surface [123–127]. Anodization produces modifications in
the microstructure and the crystallinity of the Titanium
oxide layer [128]. The anodization process is rather com-
plex and depends on various parameters such as current
density, concentration of acids, composition, and elec-
trolyte temperature.
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Anodized surfaces result in a strong reinforcement of the
bone response with higher values for biomechanical and
histomorphometric tests in comparison to machined sur-
faces [129, 130]. A higher clinical success rate was ob-
served for the anodized Titanium implants in comparison
with turned Titanium surfaces of similar shapes [131]. Two
mechanisms have been proposed to explain this osseoin-
tegration: mechanical interlocking through bone growth in
pores and biochemical bonding [129, 132].
In 2008, Elias et al. investigated, through in vivo and
in vitro tests, the behavior of machined Titanium dental
implant samples submitted to lasting treatments, acid
etching, and anodizing that changed the surface mor-
phology. The results have shown that the surface roughness
and wettability of implants may influence biological re-
sponses such as the removal torque of dental implants
[133].
Recently Aparicio et al. [134] reported on the in vivo
histological and mechanical performance of Titanium
dental implants with a new surface treatment (2 step)
consisting of an initial blasting process to produce a micro-
rough surface, followed by a combined chemical (alkaline
etching) and thermal treatment (600 °C, for 1 h) that pro-
duces a potentially bioactive surface. They demonstrated
that the 2-step treatment produced micro-rough and
bioactive implants (Fig. 2) that accelerated bone tissue
regeneration and increased mechanical retention (Fig. 3) in
the bone bed at short periods of implantation in comparison
with all other implants tested (as-machined, acid etched,
and blasted Titanium).
Titanium surface coating
Different methods have been developed to coat metal im-
plants: plasma spraying, sputter deposition, sol–gel coat-
ing, electrophoretic deposition, or biomimetic
precipitation. However, only the plasma-spraying coating
method has been used for Titanium dental implants in
clinical practice. Plasma-sprayed coatings can be deposited
with a thickness ranging from a few micrometers to a few
millimeters. Coating delamination is one of the main
concerns of this method; and for this reason, plasma-
sprayed coating is often associated with implant roughen-
ing, e.g., by means of blasting.
Inorganic components as coating are looked at as being
particularly interesting for various reasons. Calcium plays a
relevant role in the binding process of biologically active
proteins from the peri-implant milieu as in its ionized form
it adsorbs to the TiO2 surface and further to macro-
molecules with high affinity for Ca2? [135, 136]. Ap-
proaches to incorporate calcium and phosphates onto
implant surfaces have a rather long history of calcium
phosphate coatings. It is well recognized that calcium
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4786 J Mater Sci (2015) 50:4779–4812

Fig. 2 SEM pictures of a as-machined, b acid etched, c blasted, and d 2-step Titanium surface surfaces before being implanted. Notable
differences in the topography of the implants depending on the surface treatment can be observed. Reprinted from Ref. [135] with permission

Fig. 3 Pullout test of cylindrical implants. During the pullout tests machined or acid-etched cylinders were tested (b). Reprinted from
parts of bone remained attached to the surfaces of some of GBlast and Ref. [135] with permission
2-step cylinders (a). This same occurrence did not happen when as-

phosphate Ca10(PO4)6(OH)2 (HA hydroxyapatite) coatings
have led to better clinical success rates in the long-term
than uncoated Titanium implants [137, 138]. These long-
term success rates are due to a superior initial rate of
osseointegration [138].
Plasma-sprayed HA coatings are usually composed of
large crystalline HA particles embedded into a highly
soluble amorphous calcium phosphate phase. Moreover,
the plasma-spraying technique is not very effective for
coating tiny dental implants with a complex shape. Plasma-
sprayed HA-coated dental implants have also been asso-
ciated with clinical problems [139–143]. As already stated,
one of the major concerns with plasma-sprayed coatings is
the possible delamination of the coating from the surface of
the Titanium implant and failure at the implant-coating
interface despite the fact that the coating is well attached to
the bone tissue. The discrepancy in dissolution between the
various phases that make up the coating has led to de-
lamination, particle release, and thus the clinical failure of
implants [140–143]. Coating delamination has been

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J Mater Sci (2015) 50:4779–4812
reported in dental situations where the efficacy of plasma
spraying is not optimal due to the size of the dental im-
plants [143]. Loosening of the coating has also been re-
ported, especially when the implants have been inserted
into dense bone.
For all of the above reasons, the clinical use of plasma-
sprayed HA-coated dental implants is limited. Many clin-
ical studies were reported for HA-coated implants [144–
146]. They have higher integration rate, promote faster
bone attachment, and achieve direct bone bonding, when
compared to uncoated [147]. However, there are many
controversies regarding the long-term prognosis of coated
dental implants. For example, an 8-year [148] clinical
retrospective study of Titanium plasma sprayed with hy-
droxyapatite-coated implants showed that the survival rate
was initially higher for HA-coated implants, but decreased
significantly after 4 years of implantation. Most of long-
term failures were due to inflammatory reaction. Tsui et al.
[149, 150] report some metastable and amorphous phases
that appear in the HA coating during the plasma-spraying
process, which results in the low crystallinity of HA
coating and poor mechanical strength [151]. Despite their
negative reputation in dental practice, a meta-analytic re-
view did not show that long-term survival rates were in-
ferior for plasma-sprayed HA-coated dental implants
compared to other types of dental implant [142].
Over the past decade, Santos et al. have reported and
developed a glass-reinforced HA composite by incorpo-
rating CaO–P2O5-based glass into the microstructure of
HA through a simple liquid phase sintering process [152,
153] and this material was patented and recently regis-
tered as BonelikeÒ [154]. This system allows the incor-
poration of several ions, such as magnesium, sodium, and
fluoride resulting in a bone graft with a chemical com-
position similar to the mineral phase of bone. This novel
biomaterial as a result of its controlled chemical phase
composition of HA, a and b-tricalcium phosphate (TCP),
and its microstructure was endowed with better me-
chanical properties and enhanced bioactivity than the
current commercially available HA [155]. Lobato et al.
[156] evaluated the direct bone bonding and osseointe-
gration of the commercially pure (cp Ti) implants coated
with BonelikeÒ placing them in the mandible of a
40-year-old patient. The interfaces between dental im-
plant/BonelikeÒ coating, and BonelikeÒ coating/new bone
were evaluated using scanning electron microscopy. Mi-
crostructure observations of BonelikeÒ coated dental im-
plants demonstrated the presence of remarkable bone
remnants along the coating surface. An improved primary
stability of the coated implants was also observed, sug-
gesting that the BonelikeÒ may play a significant role in
the new bone formation process around the dental im-
plants (Fig. 4).
4787
However, further evidence to be achieved by properly
designed Clinical Trials is strongly recommended, before
the introduction to everyday practice.
Another technique for surface modification is ion im-
plantation. Exhaustive details on this technique are re-
viewed elsewhere [157].
It comprises high-vacuum technology that can be ap-
plied under controlled temperature conditions. The tech-
nique involves the bombardment of a surface with ions that
have been previously selected and accelerated to high ve-
locities. The ions disrupt the surface of the material due to
their high kinetic energy, penetrating, and becoming im-
planted within its atomic network—a phenomenon that
implies modifications in the most superficial layers of the
material. The implanted zone forms an integrated part of
the material, thus avoiding the risk of delamination asso-
ciated with other coating techniques. Furthermore, there is
no material loss with such processes—a fact that affords
advantages over material removal techniques. The benefits
derived from these surface changes are mechanical (with
increased resistance to wear and friction, increased mate-
rial hardness), chemical (increased resistance to corrosion,
less lixiviation), electrochemical (enhanced ionic stability),
and biological (better tissue adsorption) [158, 159]. For
example, set of different elements such as Au, N, C, CO,
and Ne have been ion implanted in dental implants
manufactured on Ti–6Al–4V alloy [158, 160].
The authors concluded that CO ion implantation has
modified and enhanced the outer surface oxide in a way
that promotes bone formation, and thus the osseointegra-
tion of the Ti–6Al–4V dental implants. By allowing the
selection of the ions most suitable to the desired charac-
teristics, ion implantation is clean, versatile, highly con-
trollable, and reproducible. Also, it induces intrinsic
modifications within the most superficial layers, while
preserving the structure and characteristics of the back-
ground material.
In a recent article, de Maeztu et al. [161] compared
carbon–oxygen (CO) ion implantation as a surface treat-
ment with diamond-like carbon and commercially treated
implants, including double acid etched (OsseotiteÒ), an-
odized (TiUniteÒ), and blasted and acid etched (SLAÒ),
using machined Titanium implants as control. Values of
percentage BIC were higher in a statistically significant
way in implants treated with CO ion implantation com-
pared to the commercially treated implant group and the
control implants at 3 and 6 months, respectively.
In general, although the ion implantation is expensive, it
is extremely controllable and can be tailored to implant
ions to form ultra-high-purity coating layers. Future in-
vestigations should include clinical experiments to deepen
the knowledge of bone responses to coated implant sur-
faces [157].
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4788
Fig. 4 SEM image shows a, b an extensive new bone formation and
well-adherent BonelikeÒ\coating to the Ti implant. Bone was apposed
on the coating; c a thick coating well attached to substrate. No
significant BonelikeÒ\coating dissolution after 6 months implanta-
tion; d new bone has grown through the micro- and macro-porosity of
BonelikeÒ\coating, which remained attached to the substrate; e an
Future trends in Titanium dental implant surfaces
In a few recent reviews [6, 8, 162], some strategies are
proposed to increase quality and rate of osseointegration of
Titanium dental implants. These future trends concern (1)
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J Mater Sci (2015) 50:4779–4812
extensive new bone formation which was apposed onto BonelikeÒ\-
coating without the formation of gaps at the interface at 9200
magnification; and f new bone formed with a high degree of
maturation after 3 months implantation as obtained at 9400 magni-
fication (NB new bone). Reprinted from Ref. [157] with permission
the modification of surface roughness at the nanoscale level
for promoting protein adsorption and cell adhesion [163–
167]; (2) biomimetic calcium phosphate coatings [168–
180] for enhancing osteoconduction; (3) the incorporation
of biological drugs for accelerating the bone healing
J Mater Sci (2015) 50:4779–4812 4789

process in the peri-implant area [181–188]; and (4) the growth factor (PDGF), and insulin-like growth
inclusion of nanoparticles [189–192] organic components factors (IGF-1 and 2) are some of the most
such as chlorhexidine and polysaccharides, among which promising candidates for this purpose [181–188,
particular emphasis is given to chitosan [193–198]. 211]. The limiting factor is that the active product
has to be released progressively and not in a single
(1) The use of nanotopographical modifications on the
burst.
implant surface to induce intrinsic osteoinductive
(4) Recent investigations have reported that the appli-
signaling of the surface adherent cells is an approach
cation of bioactive agents may result in enhanced
of current interest. Existing data supporting the role
osteogenic properties to the implant surface [212,
of nanotopography suggest that critical steps in
213]. Bioactive implants have been reported to
osseointegration can be modulated by nanoscale
possibly develop a biochemical bonding between the
modification of the implant surface [199–201]. Such
bone tissue and the titanium implant surface rather
changes alter the implant’s surface interaction with
than a merely physical one [215, 216]. A bioactive
ions, proteins (i.e., adsorption, configuration, bioac-
implant surface is defined as one that has the
tivity, etc.), and cells.
potential to promote numerous molecular interac-
These interactions can favorably influence mole-
tions, potentially forming a chemical bond between
cular and cellular activities and alter the process of
bone and implant surface [215]. Some studies have
osseointegration. Several techniques and approaches
demonstrated that proteins or peptides with bioactive
are used currently to produce nanotopographic
capacity such as bone morphogenetic proteins
modifications of endosseous implants [202]. Some
(BMPs), fibronectin, type I collagen, fibroblast
of these approaches involve physical methods of
growth factor (FGF), and arginine-glycine-aspartic
compaction of ceramic particles to yield surfaces
acid (RDG peptide) are promising bioactive mole-
with nanoscale grain boundaries [203], chemical
cular candidates with a high osteogenic potential
treatments [204], innovative sandblasting/acid etch-
[216, 217]. Preliminary approaches of matrix engi-
ing [205], optical lithography [206], galvanostatic
neering have been employed by a combination of
anodization [207] crystal deposition [208], and
RGD peptides (arginine, glycine, and aspartate)
monolayers to expose functional end groups that
using acrylate anchors and the nanomechanical
have specific functions [209]. A limitation of some
anchorage of collagen I fibers [162] resulting in
of these methods is that they are random processes,
increased bone-implant contact and bone density
so it is hard to control the uniformity and distribution
during early stages of peri-implant bone formation
of nanostructures on the implant surfaces.
already after one month (Fig. 5a, b). Being able to
(2) Scientists have developed a new coating method
promote cell adhesion via integrins—i.e., transmem-
inspired by the natural process of biomineralization.
brane receptors fundamental for cell-extracellular
In this biomimetic method, the precipitation of
matrix interactions—arginylglycylaspartic acid
calcium phosphate apatite crystals onto the titanium
tripeptide has been intensively researched on the
surface from simulated body fluids (SBF) formed a
in vitro level and in preclinical animal models [218,
coating at room temperature. In order to accelerate
219].
the deposition of coatings from aqueous solutions,
several methods have been developed and are However, the fabrication of these bioactive molecules
reported elsewhere [168–177]. The osseointegration and economic feasibility along with technical and regula-
of titanium implants coated with biomimetic calcium tory issues have led researchers to explore alternative
phosphate has been investigated in preclinical com- bioactive molecules such as the bone-mobilizing hor-
parative models [178, 210]. However, the osseoin- mone—vitamin D [220–225].
tegration of titanium dental implants coated Masuyama et al. [221] showed that Vitamin D in its
biomimetically has not yet been compared with active form could regulate collagen modification and
other surface treatments in preclinical models. maturation in an osteoblastic cell culture, which has been
(3) The surface of titanium dental implants may be proven to be important in early bone formation [217].
coated with bone-stimulating agents such as growth
factors in order to enhance the bone healing process Drawback of Titanium implants
locally. Members of the transforming growth factor
(TGF-) superfamily, and in particular bone morpho- Titanium implants have the longest traceable record of
genetic proteins (BMPs), TGF-1, platelet-derived predictable clinical performance with a cumulative success

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4790
Fig. 5 Bone–implant interface of a machined Ti implant with Coll
I/RGD coating. A thick and continuous layer of bone is visible on the
implant surface (black) (a). Bone–implant interface of an uncoated
rate of 98.8 % for 15 years [226]. This is attributed to high
biocompatibility, favorable bone and soft tissue response,
and adequate strength and corrosion resistance of cpTi and
Ti–6Al–4V. Only recently, there has been a move toward
seeking alternatives to cpTi and Ti–6Al–4V. This has been
instigated in order to counteract some drawbacks associ-
ated with Titanium dental implants. Andreiotelli et al.
[227] classified those drawbacks as the following: esthetic
challenge, health issues, and progress in bioceramic
development.
Esthetic challenge The fact that ceramic materials are
white and are mimicking natural teeth better than the gray
Titanium allows an ‘improved’ esthetic reconstruction for
patients. Using white ceramic implants would preclude the
dark shimmer of Titanium implants when the soft mucosa
is of thin biotype or recedes over time [228–230]. In lit-
erature, the correction of esthetic complication is reported
using autografting with subepithelial connective tissue or
xenogeneic collagen matrix of porcine origin to augment
the keratinized tissue around implants [231, 232], albeit
there is no strong evidence that the grafting increases soft
tissue thickness.
Health issues Titanium is no longer considered as com-
pletely bioinert material, instead it might be an allergen as
reported by several studies [233–236]. Elevated Titanium
concentrations have been found in the vicinity of oral im-
plants [236], in regional lymph nodes [237], serum, and
urine [238], which is potentially hazardous to human body.
However, the clinical relevance of the above findings is not
clear yet, since numerous investigations have so far sup-
ported the reliability of Titanium for long-term use in the
oral environment [239]. These concerns, together with the
esthetic issue, have rendered some dental patient metal
phobic requesting for treatment with completely metal-free
dental implants [240].
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J Mater Sci (2015) 50:4779–4812
machined Ti implant. Sparse and thin bone regenerates are visible
with only minor contact to the implant surface (black) (b). Reprinted
from Ref [163] with permission
Progress in ceramic development In the last three dec-
ades, research and manufacturing technology have allowed
production of advanced bioceramic. The key steps in the
growing of their popularity are the introduction of new
materials such as Yttria partially stabilized tetragonal Zir-
conia polycrystals (Y–TZP), Zirconia toughened Alumina
(ZTA), and new manufacturing techniques such as Powder
Injection Molding (PIM) [241] and Hot Isostatic Pressing
(HIP).
Ceramic materials
Ceramic materials for oral implants were already investi-
gated and clinically used some 30–40 years ago [242, 243].
At that time, the ceramic material utilized was aluminum
oxide (Alumina), but currently the material of choice is
Yttria-stabilized tetragonal Zirconia polycrystal (Y–TZP).
A proposed ceramic material is Ce–TZP (ceria stabilized
TZP) [244] but neither in vitro data, nor in vivo tests have
been published so far.
Alumina
High-density, high-purity ([99.5 %) Al2O3 was chosen for
dental implant manufacturing because of its combination of
excellent corrosion resistance, good compatibility, high
wear resistance, and high strength. Although some dental
implants (presently withdrawn from the market [227]) were
made of single-crystal sapphire characterized by a glassy
appearance, major interest in literature was shown for fine-
grained polycrystalline a-Alumina (a-Al2O3) produced by
pressing and sintering at temperatures ranging from 1600
to 1800 °C (depending upon the properties of the raw
material).
When preparing Alumina bulk material, to achieve a
fully dense sintered body with a fine grain microstructure, a
very small amount of MgO (\0.5 %) should be used as a
J Mater Sci (2015) 50:4779–4812
grain growth inhibitor. Likewise, the amount of SiO2 and
alkali oxides ought to be kept below 0.1 %, as they impede
densification and promote grain growth. Also the amount
of CaO has to be below 0.1 %, since its presence lead to the
lowering of the static fatigue resistance. [245].
Strength, fatigue resistance, and fracture toughness of
polycrystalline a-Alumina are function of grain size and
percentage of sintering aid, i.e., purity. Alumina has a
density of approximately 4 g/cm3, a Vickers hardness of
2300, a compressive strength of 4400 MPa, a bending
strength of 500 MPa, a modulus of elasticity of 420 GPa,
and a fracture toughness (KIC) of 4 MPam1/2.
Anyway, the high hardness and modulus of elasticity
make the material brittle. Combined with the relatively low
bending strength and fracture toughness, the material is
prone to fracture when loaded unfavorably. This might be
the reason why dentists do not use Alumina implants. In-
terestingly, however, fracture was seldom mentioned in the
literature as a reason for implant loss [246–248].
Extensive preclinical (animal) and clinical investiga-
tions were performed to evaluate Alumina regarding its
use as an oral implant material. In different rabbit and
dog models, the Alumina did osseointegrate similarly in
comparison to Titanium or hydroxyapatite [249]. Clinical
investigations using Alumina implants up to 10 years
showed survival/success rates in the range of 23–98 % in
dependence of patient characteristic (single tooth re-
placement, partially dentate patients, and edentulous pa-
tients) [227]. The overall survival rate of Alumina
implants was lower than that of Titanium implants as
assessed in a series of systematic reviews where 95.4 %
of the implant supported single crowns and 96.8 % of the
implant supported fixed partial dentures survived at
5 years [250–252]. The only exception where long-term
survival rates with Alumina implants were comparable to
Titanium implants is the investigations by Fartash et al.
[247, 253].
To the knowledge of the authors, however, no Alumina
implant system is marketed anymore [227]. The Bio-
ceramÒ made of single-crystal sapphire implant was
withdrawn from the market. It is also interesting to notice
that no preclinical investigations dealing with the me-
chanical stability of Alumina ceramic implants could be
found in literature.
Zirconia
Structure and properties The name of the metal zirconi-
um originates from the Arabic ‘‘zargun’’ (golden in color),
which in turn comes from the two Persian words Zar (gold)
and Gun (color). Zirconia, the metal dioxide (ZrO2), was
identified as such in 1789 by the German chemist Martin
Heinrich Klaproth in the reaction product obtained after
4791
heating some gems [254]. Its mechanical properties are
close to those of metals [254]. In 1975, Garvie et al. pro-
posed a model to rationalize the good mechanical proper-
ties of Zirconia, by virtue of which it has been called
‘‘ceramic steel’’ [255].
At ambient pressure, unalloyed Zirconia can assume
three crystallographic forms depending on the temperature.
At room temperature and upon heating up to 1170 °C, the
symmetry is monoclinic (P21/c). The structure is tetragonal
(P42/nmc) between 1170 and 2370 °C and cubic (Fm3m)
above 2370 °C and up to the melting point [256, 257]. The
transformation from the tetragonal (t) to the monoclinic
(m) phase upon cooling is accompanied by a substantial
increase in volume (*4.5 %), sufficient to lead to catas-
trophic failure. This transformation is reversible and begins
at *950 °C on cooling. Alloying pure Zirconia with sta-
bilizing oxides such as CaO, MgO, Y2O3, or CeO2 allows
the retention of the tetragonal structure at room tem-
perature and therefore the control of the stress-induced
t ? m transformation, efficiently arresting crack propaga-
tion and leading to high toughness [258, 259]. Anyway,
tetragonal form cannot withstand more stress. When a
crack develops, tetragonal grains convert immediately to
monoclinic form. As the crack propagates, sufficient stress
develops within the tetragonal structure and the grains
around the crack transform to stable monoclinic form. In
this process, expansion volume of zirconium dioxide
crystals occurs, which produces compressive stress around
the crack preventing further propagation [254, 260, 261].
This mechanism is known as Transformation toughening
and is influenced by temperature, vapor, particle size, mi-
cro- and macrostructure, and concentration of stabilizing
oxides [262].
Among the stabilized Zirconia, Yttria-stabilized Zirco-
nia (Y–TZP) ceramics [263] present excellent mechanical
and tribological properties together with biocompatibility
and are correctly regarded as a good choice for preparing
dental implants. Adding Yttria to Zirconia decreases the
driving force of the t–m transformation and hence its
temperature, as shown in the ZrO2–Y2O3 diagram in Fig. 6
[264].
Biomedical grade Zirconia usually contains 3 mol%
Yttria (Y2O3) as a stabilizer (3Y–TZP or ZrO2–YO1.5)
[264]. While the stabilizing Y3? cations and Zr4? are
randomly distributed over the cationic sites, electrical
neutrality is achieved by the creation of oxygen vacancies
[265, 266].
The mechanical properties are well above those of all
other available dental ceramics, with a flexural strength in
the 800–1000 MPa range and a fracture toughness in the
6–8 MPam0.5 range. The Weibull modulus strongly de-
pends on the type of surface finish and the processing
conditions [267].
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4792
Fig. 6 ZrO2–YO1.5 phase diagram. Metastable phases retained at
room temperature are indicated just above the horizontal axis. The red
dotted lines show the nonequilibrium monoclinic-tetragonal and
cubic-tetragonal transition regions. Reprinted from Ref. [264] with
permission
Despite the excellent mechanical properties and the fact
that many studies deem Zirconia a promising biomaterial
[268, 269], there is still a huge concern about the long-term
durability of the material. In fact, the future of Y–TZP ma-
terials has been questioned recently, due to the reports of
their in vivo failures [270–272]. These problems were caused
by the low-temperature degradation (LTD) of Zirconia. LTD
of Zirconia, also called ‘‘ageing process,’’ is a well-
documented phenomenon [273–278] and basically involves
the t ? m transformation. Indeed, this process can be fa-
vored, even at room temperature, by the presence of water
[279] always available in vivo. The penetration of water
radicals into Zirconia lattice leads to the formation of tensile
stresses in Zirconia surfaces. Consequently, the activation
barrier for the transformation is lowered, and the phase
transition is promoted. The results of this aging process are
multiple and include surface degradation with grain pullout
and microcracking as well as strength degradation.
It has been proven that stabilizer type and content,
residual stress, and grain size are the main factors
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J Mater Sci (2015) 50:4779–4812
controlling the aging phenomenon [280]. An in vitro ex-
periment has shown that Young’s modulus and hardness of
Y–TZP bars were reduced by 30 % when they were sub-
jected to hydrothermal cycling. The authors also concluded
that the increase of monoclinic-tetragonal phase ratio is
associated with microcracking and is responsible for the
decline in mechanical parameters [281]. Deville et al. [282]
demonstrated the influence of surface finish on the aging
kinetics of biomedical grade Zirconia. In particular, the
critical influence of polishing stages on the aging sensi-
tivity of 3Y–TZP has been systematically investigated by
optical microscopy, atomic force microscopy, and X-ray
diffraction. The aging sensitivity of biomedical grade Zir-
conia is directly linked to the type (compressive or tensile)
and amount of residual stresses. Rough polishing produces
a compressive surface stress layer beneficial for the ageing
resistance, while smooth polishing produces preferential
transformation nucleation around scratches, due to elas-
tic/plastic damage tensile residual stresses. The AFM
height image (Fig. 7) clearly reveals that the various
monoclinic spots nucleate preferentially along the
scratches.
On the other hand, several studies showed that aging can
be minimized to biologically acceptable levels by opti-
mizing manufacturing process, recurring to proper crystal
size, removing impurities, and embracing the use of var-
ious aging-resistant material [282].
Furthermore, Zirconia blanks showed no significant
deterioration in mechanical properties after being embed-
ded into the medullary cavity of the tibia of rabbits for a
period of 30 months. It was also reported that Zirconia can
be used clinically as it retains a bending strength of over
700 MPa after being immersed in 95 °C saline solution for
over 3 years [283].
Finally, Jerome Chevalier, one of the leading researcher
in the field of Zirconia aging, concluded in his extensive
review that ‘‘although in the 1990s 3Y–TZP ceramics were
considered very promising materials for biomedical appli-
cations, long-term follow-up is needed to address the cri-
tical problem of aging in vivo. In the meantime, new
Zirconia or Zirconia-based materials that overcome the
major drawback of the standard 3Y–TZP are now avail-
able’’ [276].
Hot isostatic press (HIP) is the most common method
used for preparing Zirconia dental implants. By subjecting
pressed powder, or sintered parts with remaining porosity,
to inert gas at isostatic pressure at a high temperature
(HIPing), the density increases and is said to be an excel-
lent method for making high-density homogenous products
[284]. HIPing makes possible to apply the pressure equally
from all directions resulting in greater material uniformity
and higher strength [285]. It has been stated that HIPing of
Y–TZP Zirconia enhances the strength, eliminates such
J Mater Sci (2015) 50:4779–4812
Fig. 7 AFM micrographs of the progressive nucleation and growth of monoclinic phase after a 40, b 60, c 80, and d 100 min at 140 °C,
revealing that the various monoclinic spots nucleate preferentially along the scratches. Reprinted from Ref. [282] with permission
fracture sources as pores and, as mentioned above, reduces
the undesirable aging phenomenon [286]. Y–TZP blocks
are prepared by presintering at temperatures below
1500 °C to reach a density of at least 95 % of the theore-
tical density. The blocks are then processed with hot iso-
static pressing (HIP) at temperatures between 1400 and
1500 °C under high pressure. A high isostatic pressing
(HIP) cycle after sintering is recommended to the
manufacturing process of Zirconia to reach a full density
close to the theoretical one (d = 6.1 g/cm3). As, Y–TZP
usually results in a gray–black material, a subsequent heat
treatment in air is needed to restore the whiteness of the
material by oxidation. The density of the HIPed Y–TZP
prefabricated blanks pressed in the way described above
was, according to the manufacturer’s information, 6.09 g/
cm3. The blocks can then be machined using a specially
designed milling system.
Due to the high hardness and low machinability of fully
sintered Y–TZP, the milling system has to be particularly robust
[287–290]. Moreover, the fine grain size of Y–TZP leads to
very smooth surfaces after machining [291]. The transfer of
modern computer aided design/computer aided manufacturing
4793
(CAD/CAM) technology into dentistry gives the possibility to
avoid HIPing [292]. The majority of the available dental CAD/
CAM systems employ partly sintered Yttria-stabilized te-
tragonal Zirconia polycrystal (Y–TZP) blanks, making milling
processes faster, and reducing the wear on the hardware,
compared with systems employing densely sintered blanks
(HIP process). The CAD/CAM technology, however, needs to
compensate for the final sintering shrinkage by enlarging the
original shape before milling (*20–25 %), whereas this is not
necessary with the HIPed Y–TZP blanks, which can be ground
to the desired size directly [293, 294]
The salient mechanical properties of Y–TZP either
pressureless sintered or sintered and high isostatically
pressed are presented [261] in Table 4.
In vitro, In vivo, and clinical test
As already stated, Zirconia showed a high level of bio-
compatibility. In vitro experiments on different cell lines,
in vivo studies on animals, and clinical studies on humans
proved the safety of this material. Evidence from in vitro
studies maintained the osteoconductivity of Zirconia
123
4794
Table 4 Comparison of several
mechanical properties of Yttria-
stabilized Zirconia (Y–TZP) Density (g/cm3)
either pressureless sintered or
sintered and high isostatically Average grain size (lm)
pressed [255] Microhardness (Vickers)
Young’s modulus (GPa)
Bending strength (MPa)
Toughness KIC (MPa m1/2)
ceramics [295, 296]. In their preliminary in vitro investi-
gation, Kohal et al. [297] concluded that one-piece Zirco-
nia implants restored with all ceramic crowns possibly
fulfilled the biomechanical requirements for anterior teeth.
In another study, mean fracture strength of Zirconia im-
plants was investigated after chewing simulation and found
to be within the limits of clinical acceptance. However,
preparation of a one-piece Zirconia implant to receive a
prosthesis significantly compromised fracture strength. The
authors concluded that long-term clinical data were nec-
essary before one-piece Zirconia implants could be rec-
ommended for clinical practice [298]. Two-piece Zirconia
implants were considered clinically inadequate owing to
the increased risk of fracture at the level of the implant
head [299].
When implanted in bone or soft tissues, the latter react
favorably with undetectable residue release and almost no
fibrous encapsulation and inflammatory reactions are ob-
served [300]. An animal study conducted by Scarano et al.
[301] found that unloaded Zirconia implants osseointegrate
when inserted in rabbit’s tibia bones without any signs of
inflammation or mobility. Sennerby et al. [302] reported
superior osseointegration of modified (roughened) Zirconia
implants when compared to machined ones and similar
resistance to removal when compared to oxidized Titanium
implants. Loaded Zirconia implants were studied and
compared to Titanium ones by Kohal et al. [303] who
concluded that there was no difference as for osseointe-
gration level between the two groups. In contrast, Akagwa
et al. [304] reported evident crestal bone loss around
loaded Zirconia implants when compared to an unloaded
group. Yet, bone-implant contact of the two groups was
similar in this study. Five years later, the same research
group reported possible long-term and stable osseointe-
gration of loaded and unloaded Zirconia implants [305].
Clinical studies on Zirconia implants are scarce, and the
quality of evidence they provide is questionable. Unsur-
prisingly, the major setbacks of these studies were short
follow-up period and/or small sample size. In the system-
atic review by Andreiotelli et al. [228], only three retro-
spective cohort studies on one-piece Zirconia dental
implants met their inclusion criteria. The first two studies
were by Mellinghoff et al. [306] and Oliva et al. [307] who
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J Mater Sci (2015) 50:4779–4812
Pressureless sintered Y–TZP HIPed Y–TZP
6 6.1
\1 \0.5
1000–1200 1000–1300
200 200
800 1200
9–10 9–10
investigated 189 and 100 Zirconia implants and found
1-year survival rates of 93 and 98 %, respectively. Most
failed implants did so in the healing phase, in which in-
creased mobility was noticed. Only one implant failed after
prosthetic reconstruction due to implant fracture.
Lambrich and Iglhaut [308] followed up 127 Zirconia
and 234 Titanium implants for a mean observation period
of 21.4 months. In this study, Zirconia implants performed
as well as Titanium counterparts when inserted in mandible
(98.4 vs. 97.2 %), while Titanium implants performed
significantly better in the maxilla (98.4 vs. 84.4 %). Again,
all failures were in the healing phase due to increased
implant mobility. These findings have been confirmed re-
cently by Depprich et al. [309] who found only 17 clinical
studies on Zirconia implants conducted between 2006 and
2011, in which survival rate was between 74 and 98 %
after 12 and 56 months. Payer et al. [310] reported 95 %
2-year survival according to the clinical and radiographic
parameters they examined, in 19 immediately loaded Zir-
conia implants. These results are consistent with the data
published by Oliva et al. [311] who followed up 831 one-
piece Zirconia implants placed in 371 patients for 5 years
and found a survival rate of 95 %. On the contrary, Kohal
et al. [312] found that immediately restored one-piece
Zirconia implants have 1-year cumulative survival rate
comparable to Titanium counterparts.
Although successful osseointegration of Y–TZP has
been demonstrated in several studies, efforts have been
made to roughen the implant surface textures to improve its
osseointegration, as with Titanium and Titanium alloy
implants. The fabrication of medical grade Zirconia rods
usually results in a relatively smooth surface combined
with the bioinert nature of the material. This renders the
surface of the resulting implants dense and non-retentive
[313]. Thus, numerous surface modification approaches,
such as sandblasting [303, 314] and acid etching [313,
315], are currently being used to increase the surface
roughness of machined Zirconia implants with the goal of
improving osseointegration. However, because Zirconia
biomaterial is particularly hard, it can be difficult to
achieve sufficient roughness in Zirconia implants using the
conventional means typical for Titanium implants [316].
Özkurt et al. [317] reviewed clinical and research articles
J Mater Sci (2015) 50:4779–4812
on Zirconia dental implants with and without different
surface treatments, comparing them with Titanium dental
implants, and provided information on Zirconia dental
implant osseointegration and mechanical strength. In the
work published by Oliva et al. [311], three different groups
of implants with different surface roughness were investi-
gated. The acid-etched implants were found to be superior
to the coated and machined ones. Zirconia dental implants
may possibly substitute, at least in part Titanium dental
implants, but they are not yet in routine clinical use.
New process technology for Zirconia: powder injection
molding (PIM)
An alternative to classical machining for preparing Zirco-
nia and other ceramics is the Powder injection molding
(PIM), also called ceramic injection molding (CIM). PIM
is a combination of powder technology and injection
molding. The process is a shape processing technique that
allows the low-cost manufacture of ceramic components
with complex shapes [318–320]. It involves several stages,
namely mixing, injection molding, debinding, and sinter-
ing. According to the kind of organic additive, the resulting
powder–binder mixtures, the so-called feedstocks, are
suited for the one or the other plastic shaping method.
These methods are divided into low-pressure (LPIM) and
high-pressure injection molding (HPIM), according to the
viscosity of the feedstocks and the resulting injection
pressure. Applied injection pressures between 0.2 and
5 MPa are counted as the low-pressure area of the injection
molding technique. A catalog of advantages and disad-
vantages from different steps of production has been re-
viewed [321–325].
As occurs for all the powder technological processing
routes, the choice of the ceramic powder plays a dominant
role for PIM. Specific surface area, particle size, size dis-
tribution, particle shape, and purity of the powder influence
the properties of the injection molding mass, such as the
sintering behavior and the final properties of the ceramic
component. Even slight changes in the particle shape, the
size distribution, or the humidity of the air may influence
the rheological behavior of the feedstock [326]. Typical
particle sizes in ceramic injection molding are 1–2 lm
[326], but also the use of much finer particles down to
submicron or nano region has been reported [327]. Besides
the average particle size, the width of the particle size
distribution is important. According to German [328], very
wide or very narrow size distributions prove easier to mold.
To ensure quality, the debinding [329] process must be
carefully performed to avoid component distortion, crack-
ing, blistering, and contamination of parts. This entails a
long processing period, thereby prompting the develop-
ment of different debinding techniques, including solvent,
4795
thermal, wicking, evaporation and catalytic debinding, as
well as the combination of these approaches [330–335].
The use of a multicomponent binder system enables two-
stage binder removal [336, 337]. The main binder (back-
bone component) is usually a thermoplastic material that
maintains the shape of the injected parts by confining ce-
ramic powder particles. It is then thermally removed during
the first debinding stage. The support binder (commonly a
wax), which functions as a filler phase, is eliminated during
the first debinding stage by immersing the injected part in a
solvent, such as heptane, hexane, and kerosene.
Park et al. introduced the PIM for preparing rough
surface Zirconia dental implants and showed promising
results in an in vivo rabbit experiment [338]. The same
group evaluated the osseointegration in rabbit tibiae and
investigated surface characteristics of novel Zirconia im-
plants made by PIM technique, using molds with and
without roughened inner surfaces, comparing the results
with those obtained using a machined Titanium implants.
The SEM image of Zirconia surface using a roughened
mold demonstrated (Fig. 8a, b) elevations and depressions
as well as the typical grain structure found in the as-sin-
tered Zirconia (Fig. 8c, d). This corresponds to sig-
nificantly higher removal torque values for PIM Zirconia
implants obtained with the roughened mold versus those
fabricated without the roughened mold. Moreover, Zirco-
nia implants exhibited significantly higher bone-to-implant
contact and removal torque values than the machined Ti-
tanium implants. The osseointegration of PIM Zirconia
implant was considered promising.
Jum’ah et al. [339] recently reported the procedure of
immediate post-extraction replacement of maxillary central
incisor with or without loading using a novel implant made
of Zirconia and manufactured by PIM. These implants
were blasted and acid etched so as to increase biocom-
patibility, improve osseoconductivity, and achieve better
survival in animal and human studies. Zirconia dental
implants seem to promote and maintain optimum soft and
hard tissue health and architecture, with the complete re-
spect of esthetics. Nevertheless, extensive in vitro and
clinical studies should be carried out to validate its use.
Among the multitude of surface coating materials and
technologies, Titanium, zirconium oxide ((Ti,Zr)O2) coat-
ings on implant surfaces have been introduced and used for
more than 15 years. This coating is a kind of plasma aided
physically vapored deposition of ions, and the homogenous
ion flow results in nearly monoenergetic particles of oxides
after reaction with O2 in the immediate vicinity of the
substrate surface.
The coating has been reported to exhibit a low rate of
protein denaturation and remain near neutral pH at the
implant surface [340]. Chung et al. [341] evaluate and
compare the osseointegration in rabbit tibiae of smooth and
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4796
Fig. 8 SEM micrographs of a and b PIM Zirconia implants at different magnifications and of c and d PIM Zirconia implant obtained using a
roughened mold at different magnifications. Reprinted from Ref. [338] with permission
roughened powder injection molded (PIM) Zirconia im-
plants with or without (Ti,Zr)O2 surface coatings.
They found that the (Ti,Zr)O2-coated PIM Zirconia
implants, both smooth and rough, showed enhanced his-
tological response (bone-to-implant contact) compared
with uncoated ones. On the other hand, the mechanical
anchorage was higher for rough surface implants, coated or
uncoated.
Future trend for innovative dental implant
Ti alloys (Ti–Zr and Ti–20Nb–10Zr–5Ta)
The Ti–6Al–4V alloy is considered an alternative to cpTi
because it possesses good mechanical and corrosion re-
sistance, as well as a much lower elasticity modulus than
cpTi [342]. However, there have been numerous attempts
to further improve its properties, especially those related to
elastic modulus, corrosion resistance, and biocompatibility.
Moreover, there are reports that vanadium and aluminum
ions can lead to neurological problems, such as Alzhei-
mer’s disease, and adverse reactions in tissues over an
extended period [343]. Therefore, the need exists for the
development of new Titanium alloys, mainly with the ad-
dition of niobium, molybdenum, tantalum, and zirconium,
i.e., elements that have no cytotoxicity. Studies devoted to
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J Mater Sci (2015) 50:4779–4812
alloying Titanium with these metals to develop various
binary, ternary, and quaternary alloys have intensified in
the last decade. The most promising binary alloy is Zr–Ti.
Zirconium as an endosseous implant exhibits good bio-
compatibility, as indicated by both in vitro [344, 345] and
in vivo assessments [346]. Even if considering the inevit-
ability of metal ions release during biocorrosion, toxicity of
Zr ions is acknowledged to be minimal due to the lack of
combination with biomolecules [347]. Zr is chemically
similar to Titanium; in fact, it is considered a neutral ele-
ment when added to a solid solution with Titanium because
it has an identical allotropic transformation with a similar
phase transition temperature. When in a solid solution with
Titanium, in both a and b phases, it promotes hardening
and slows the speed of phase transformation. This element
has great solubility in both crystalline phases of Titanium
and can form alloys of various proportions, as well as in-
crease mechanical strength (such as tensile strength,
hardness, and flexural strength) and improve corrosion
potential. Earlier studies have shown that the formation of
solid solutions with zirconium can decrease the a0
martensitic transformation temperature of Titanium [348,
349]. The addition of zirconium can also decrease the
melting temperature of Titanium, which can reduce the
cost of casting and swaging [350, 351]. Reducing the
melting temperature of Titanium could decrease its reac-
tivity with oxygen and reduce the risk of inadequate mold
J Mater Sci (2015) 50:4779–4812
Fig. 9 Elasticy modulus obtained at room temperature for Ti–Zr
alloy compared with cpTi and other metal and biomedical alloys.
Reprinted from Ref. [353] with permission
filling and consequent porosity development, which is due
to the large temperature difference between the molten
alloy and the much cooler investment [352]. Recently,
Correa et al. [353] analyzed the structure, microstructure,
selected mechanical properties, and biocompatibility of Ti–
Zr alloys with 5, 10, and 15 % zirconium weight. They
found that Ti–Zr alloys are formed essentially of the a0
phase (with hcp structure) and microhardness values
greater than cpTi. The elasticity modulus of the alloys was
sensitive to the zirconium concentrations while remaining
within the range of values of conventional Titanium alloys
(Fig. 9 [353]). The alloys presented no cytotoxic effects on
osteoblastic cells in the studied conditions.
Another promising alloy for dental implant is Ti–Zr–
Nb–Ta (TZNT) [354]. In general, the corrosion resistance
of quaternary Ti-based alloys is reported to be better than
that of commercial ternary [355] and of binary alloys
[356]. Moreover, metals like Nb, Ta, and Zr are found to
have good biocompatibility and osteoconductivity [357–
359] with no known adverse effect on human [360]. The
Ti–Nb–Zr–Ta alloys were reported to exhibit comparable
cell proliferation but greater cell differentiation than Ti–
6Al–4V alloy [355]. Ti–20Nb–10Zr–5Ta (TNZT) presents
improved passivity characteristics, hardness and ultimate
tensile strength (883 MPa), and lower elastic modulus
(59 GPa) respect to Ti [361, 362]. Moreover, this alloy was
shown as no detrimental effects on cell survival, apoptosis
induction, growth delay, or alkaline phosphatase activity as
Titanium, confirming that also biocompatible properties are
suitable for the use of Ti–20Nb–10Zr–5Ta in dental ap-
plications [363].
Zirconium alloy
In contrast to the conventional crystalline metals, metallic
glasses (or amorphous alloys) manifest substantially uni-
form microstructure, without defects such as dislocation
4797
and grain boundary. Periodic atomic ordering arrangement
in metallic glass only occurs in short range rather than in
long range like crystalline solids. Consequently, glassy/
amorphous alloys exhibit many unique properties, such as
high yield strength, large elastic strain (*2 %), and ex-
cellent corrosion resistance. In the light of these attractive
features, a considerable attention is paid to the potential of
Zr-based bulk metallic glasses (BMGs) as biomedical im-
plants [364–366]. Recently, a new Zr-based BMG, Zr61
Ti2Cu25Al12 (ZT1), was developed [367, 368]. From the
materials perspective, for most crystalline metals, reduc-
tion of the modulus is usually accompanied by a sacrifice in
strength. As noticed, Young’s modulus of the ZT1 BMG is
about 20 % lower than that of Ti and its alloys, more
proximal to that of the bone, together with a large elastic
strain limit. Recently, ZT1 biocompatibility was assessed
by in vitro cytotoxicity testing [369]. In terms of cellular
responses for three cell phenotypes, L929, HUVEC, and
MG63, the phenomenological behavior of cells such as
attachment, adhesion, spreading, and proliferation for the
(ZT1) metallic glass is substantially comparable to the
CpTi and Ti–6Al–4V alloy as shown in Fig. 10.
Moreover, as indicated by osteoblast gene expression of
integrin b, alkaline phosphate, and type I collagen, mRNA
level for the cells grown on ZT1 substrates is much higher
than those on the CpTi and Ti–6Al–4V alloy. It suggests
that the adhesion and differentiation of osteoblasts grown
on ZT1 are even superior to those on the CpTi and Ti–6Al–
4V alloy, therefore promoting bone formation. The good
biocompatibility of ZT1BMG is attributed to the formation
of a zirconium oxide layer on the surface and a good
corrosion resistance in physiological environment. Further
investigations on the hemocompatibility and genotoxicity,
and osseointegration by in vivo animal testing are currently
in progress.
Zirconia toughened alumina (ZTA) and alumina
toughened zirconia (AZT)
Another class of materials receiving interest as potential
bioceramics [370, 371] also for dental implant devices
[372, 373] is Alumina–Zirconia composites. They are
called either Zirconia toughened Alumina (ZTA) when
Alumina is the main component (70–95 %), or Alumina
Toughened Zirconia (ATZ), when Zirconia is the main
component. The mechanical and tribological properties and
biological safety of different ZTA and ATZ composites
have been reported in many studies during the last years
[374–384].
The benefits of these composites are the combination of
the characteristics of Alumina (high hardness, high stiff-
ness) with the mentioned properties of Zirconia, i.e., the
high strength and high toughness, with improvement of
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4798
Fig. 10 SEM micrographs of MG63 cell morphology after culture for 6 h on a ZT1, b CpTi, and c Ti–6Al–4V. d–f are high-magnification
images of a–c, respectively. Reprinted from Ref. [369] with permission
slow crack growth resistance [385]. In addition, several
studies on Alumina–Zirconia composites have remarked
the positive effect of Alumina on the hydrothermal stability
of tetragonal Zirconia phase [385, 386]. This is mainly due
to the elastic modulus of Alumina, almost twice that of Y–
TZP. Namely, the introduction of Alumina increases the
matrix stiffness, while the constraint exerted by the matrix
on Zirconia particles maintains them in the metastable te-
tragonal state [387], thus acting as ‘‘mechanical stabilizer.’’
ATZ materials show increased mechanical stability [388]
and improved aging resistance versus Y–TZP; neverthe-
less, these composites still exhibit a certain degree of aging
[388], whereas ZTA materials display much better aging
resistance than monolithic Y–TZP [388–390].
In a recent work, Vallèe et al. have proposed the func-
tionalization of ATZ and ZTA using laminin for preparing
composites suitable for dental implants. They found that
some of the most important cell kinases were induced
within the epithelial cells grown onto the two Alumina–
Zirconia composites by the presence of laminins, sug-
gesting a better cellular activation and biological activity
on treated than on untreated composites [391].
ATZ and ZTA are mainly produced using powder
pressing and slip casting and classical machining and sin-
tering. Anyway, very recently, a complete PIM process was
developed to fabricate cylindrical ZTA parts with the
multicomponent binder system on the basis of high-density
polyethylene (HDPE), paraffin wax, and stearic acid (SA).
All binders in the green parts were successfully eliminated
using a combination of solvent and thermal debinding
techniques. They studied systematically the effects of
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J Mater Sci (2015) 50:4779–4812
sintering temperature on shrinkage, the relative density,
and hardness of the sintered part (Fig. 11a–c). The relative
density and hardness values for the sintered part increased
with increasing sintering temperature. A hardness of
1582.4 HV can be achieved by sintering the ZTA parts at
1600 °C. The study showed that PIM is suitable for the
production of ZTA parts with good material properties at
optimized processing parameters [392].
Poly-ether-ether-ketone (PEEK)
Ceramic dental implants made of Zirconia seem to be a
better suitable alternative to Titanium because of its tooth-
like color, mechanical properties, biocompatibility, and
low plaque affinity [393]. However, at the moment, the
absence of a scientific consensus and the poor market share
of Y–TZP may challenge the above statement. Interest-
ingly, the systematic review of the literature by An-
dreiotelli already cited [228] (published in 2009) concluded
that the scientific clinical data were not yet sufficient to
recommend ceramic implants for routine clinical use. This
corresponds to a grade C recommendation of the defini-
tions of types of evidence originating from the US Agency
for Health Care Policy and Research [228]. Furthermore,
the stress distribution of a Zirconia implant to the sur-
rounding bone could be associated with even higher stress
peaks compared to Titanium, due to the higher elastic
modulus of Zirconia of 210 GPa [393].
The aforementioned pitfalls and other drawbacks of
ceramics induced researchers willing to avoid metals as
well to seek polymeric materials that are conveniently used
J Mater Sci (2015) 50:4779–4812
Fig. 11 Effect of sintering
temperature on shrinkage,
hardness, and relative density of
sintered ZTA part. Reprinted
from Ref. [392] with permission
in biomedical applications [394]. Among them, poly-ether-
ether-ketone (PEEK) has already been employed to replace
metallic implant components in the field of orthopedics
[395–397], traumatology [398], and for calvarial recon-
structions [399], where the mechanical conditions differ
from those traditional bone-anchored dental implants.
Presently, in the field of dentistry, clips on implant bars and
healing abutments are sometimes manufactured recurring
to PEEK [400–402].
PEEK is a high performance semi-crystalline thermo-
plastic polymer, which combines its very good strength and
stiffness with an outstanding thermal and chemical resis-
tance—e.g., against oils and acids. Being colorless and
endowed with an elastic modulus close to that of the bone,
PEEK is a viable option for dental implant manufacturing.
However, PEEK alone is generally bioinert and is not
conductive to cell adhesion [403]. Recent studies have
proposed new processing and surface modifications that
affect the biological and mechanical properties of pure
PEEK. The current experimental results on the PEEK-
based dental implants available are summarized in Table 5
[404].
Han et al., for example, have found that the biocom-
patibility of PEEK was remarkably improved after a Ti
coating was added to the surface using the e-beam depo-
sition technique [405]. The level of in vitro cellular re-
sponses, assessed in terms of the initial cell attachment,
proliferation, and osteoblastic differentiation, was found
more than doubled after Ti was deposited onto the PEEK
substrate. In Fig. 12, it is shown that the samples revealed
good cell attachment, where the red color represents the
actin in the cells, indicating good biocompatibility. How-
ever, the cells appeared to grow and spread more actively
4799
on the Ti-coated PEEK substrate (Fig. 12b) than the pure
PEEK substrate (Fig. 12a).
Nevertheless, very little is known about the long-term
results (osseointegration) and the complications related to
the use of PEEK in oral surgery. In a recent study,
Khonsari et al. [404] reported three cases of patients pre-
senting severe infectious complications after being im-
planted with intra-osseous PEEK-derived biocompatible
materials, due to poor osseointegration. Moreover, they
underlined the difficulty in managing those infections due
to the limited knowledge on the PEEK properties in dental
implantology. The implants used in the three cases were
formed by a mixture of PEEK, tricalcic phosphate (b-
TCP), and Titanium dioxyde (TiO2), which benefited from
CE marking and had their biocompatibility tested accord-
ing to ISO protocols. In vitro cytotoxicity (ISO 10993-1),
genotoxicity, carcinogenicity and reproductive toxicity
(ISO 10993-3), irritation and delayed type hypersensitivity
(ISO 10993-10), and systemic toxicity (ISO 10993-11)have
been assessed according to the manufacturer (information
available on http://www.imi-iso.com). Furthermore, these
implants complied to the norms NF EN ISO 14801-2008
(Dynamic fatigue tests for endosseous dental implants) and
NF S91-163-2000 (Biofunctionality of dental implants—
in vitro testing).
Although PEEK and its derived are currently being
evaluated in vivo and in vitro, further investigations and
definitive clinical evidence on their safety are neces-
sary. Since the osseointegration of PEEK and its
derived are not always a straightforward biological
process, experimental modulations of the surface are
mandatory to achieve the highest possible grade of
osseointegration.
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Table 5 Characteristics of PEEK-derived materials proposed for use in oral implantology

Implant type Study type Model used Results References

pPEEK CFR- In vivo Dog femur BIC: pPEEK \ Ti; CFR-PEEK \ Ti [403, 406]
PPEK
pPEEK CFR- In vivo Dog mandible BIC: pPEEK \ Ti; CFR-PEEK \ Ti [403, 407]
PEEK
CFR-PEEK In silico FEA Stress peaks: CFR-PEEK [ Ti [403, 408]
CFR-PEEK GFR- In vitro ISO 14801 protocol Stress shielding effects: CFR-PEEK \ Ti rods; GFR-PEEK \ Ti rods [409]
PEEK
HAcCFR-PEEK In vivo Rabbit femur Interfacial shear strength: HAcCFR-PEEK = grit blasted Ti allow [410]
CFR-PEEK with HA; HAcCFR-PEEK [ CFR-PEEK
pPEEK In vitro MG-63 cells Proliferation rate: pPEEK \ Ti; mRNA processing: pPEEK \ Ti [411]
nTiO2-PEEK In vitro and MG-63 cells and Bioactivity: nTiO2/PEEK [ Ti [412]
in vivo beagle dog tibia
St-HAcCFR- In vitro MG-63 cells Bioactivity: St-HAcCFR-PEEK [ Ti [413]
PEEK
nHAcPEEK In vivo Rabbit femur Osseointegration: nHAcPEEK [ Ti [414]
Implant loss: nHAcPEEK [ Ti
eTicPEEK In vitro and MC3T3-E1 cells and Cell proliferation: eTicPEEK [ Ti BIC: eTicPEEK [ Ti [415]
in vivo rabbit tibia
PEEK poly-ether-ether-ketone, pPEEK pure PEEK, BIC bone-implant contact, Ti titanium, CFR-PEEK carbon-fiber-reinforced PEEK, GFR-
PEEK glass-fiber-reinforced PEEK, FEA finite element analysis, HAcCFR-PEEK hydroxyapatite (HA)-coated CFR-PEEK, St- HAcCFR-PEEK
strontium reinforned HA-coated CFR-PEEK, nano-TiO2/PEEK, PEEK combined with nanoparticles of Titanium dioxide, nHAcPEEK
nanocrystalline HA-coated PEEK, eTicPEEK electron beam pure Titanium-coated PEEK [395]

Fig. 12 Confocal laser scanning microscopy (CLSM) images of the MC3T3-E1 cell cultured on a as-machined and b ti-coated PEEK for 3 h.
Reprinted from Ref. [405] with permission

Conclusion remarks new strategies have been proposed in order to increase

Dental implants increase the quality of life for many pa-
tients with tooth loss. The materials of choice for oral
osseointegrated implants are Titanium and Ti–6Al–4V. In
order to increase their biofunction, surface modification is
necessary because it cannot be added during manufacturing
processes. Commercially, Titanium implants with different
roughened or coated surfaces are available and recently
quality and rate of implant osseointegration.
Anyway, it has been recently pointed out that titanium
implant use may be correlated with a range of issues:
(a) potential hypersensivity to Titanium; (b) remarkable
difference between the elastic modulus of Titanium im-
plants and that of the surrounding bone, which may cause
stress in the implant–bone interface during load transfer,
possibly resulting in peri-implant bone loss; (c) esthetic

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J Mater Sci (2015) 50:4779–4812
concerns due to the Titanium opacity, which can provoke a
dark shimmer of the peri-implant soft tissue in cases of thin
biotype mucosa and/or mucosa recession around a Titani-
um implant; and (d) demand for dental reconstructions
recurring to completely metal-free materials. As a possible
alternative to Titanium, ceramics and in particular Zirconia
implants (Y–TZP) have been proposed because of their
white ‘tooth-like’ color, biocompatibility, and low plaque
affinity. The stress distribution of a Zirconia implant to the
surrounding bone could be associated with even higher
stress peaks compared to Titanium, due to the higher
elastic modulus of Zirconia. Moreover, the scientific clin-
ical data were not yet sufficient to recommend Zirconia as
substitute of Titanium implants.
For all these reasons, some new promising materials
have been considered for dental implants. Ti alloys (Ti–Zr
and Ti–20Nb–10Zr–5Ta) and Zirconium alloy (amorphous
alloy) possess good mechanical properties, exhibit good
biocompatibility, and have been proposed as an alternative
to cpTi and Ti6Al4V. Similarly, Zirconia toughened Alu-
mina (ZTA) and Alumina Toughened Zirconia (AZT) have
been considered an alternative to Zirconia. They can easily
processed by power injection molding (PIM), and ATZ
materials show increased mechanical stability and im-
proved aging resistance versus Y–TZP.
Among polymeric materials, poly-ether-ether-ketone
(PEEK) is a viable option for dental implant manufactur-
ing, being colorless and endowed with an elastic modulus
close to that of the bone. However, PEEK alone is gener-
ally bioinert and needs to be modified.
Anyway, further investigations and clinical results on
safety are necessary for these materials in order to consider
them as possible substitutes of Titanium and Zirconia for
dental implants manufacturing.
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