Titanium Alloys for Dental Implants: A Review
John W. Nicholson
Dental Materials Unit, Bart’s and the London Institute of Dentistry, Queen Mary University of London, Mile End
Road, London E1 4NS, UK and Blueﬁeld Centre for Biomaterials, 67-68 Hatton Garden, London EC1N 8JY, UK;
john.nicholson@blueﬁeldcentre.co.uk or email@example.com
Received: 14 May 2020; Accepted: 10 June 2020; Published: 15 June 2020
The topic of titanium alloys for dental implants has been reviewed. The basis of the
review was a search using PubMed, with the large number of references identiﬁed being reduced
to a manageable number by concentrating on more recent articles and reports of biocompatibility
and of implant durability. Implants made mainly from titanium have been used for the fabrication
of dental implants since around 1981. The main alloys are so-called commercially pure titanium
(cpTi) and Ti-6Al-4V, both of which give clinical success rates of up to 99% at 10 years. Both alloys
are biocompatible in contact with bone and the gingival tissues, and are capable of undergoing
osseointegration. Investigations of novel titanium alloys developed for orthopaedics show that they
oﬀer few advantages as dental implants. The main ﬁndings of this review are that the alloys cpTi
and Ti-6Al-4V are highly satisfactory materials, and that there is little scope for improvement as far
as dentistry is concerned. The conclusion is that these materials will continue to be used for dental
implants well into the foreseeable future.
titanium; alloys; dentistry; corrosion; biocompatibility; osseointegration; clinical outcomes
The topic of titanium alloys for use as dental implants has been studied. A search was carried out
through PubMed based on the key words titanium,dental and alloys, with further reﬁnements through
the keywords osseointegration,biocompatibility,corrosion and novel alloys. This gave an initial number of
7700 references, and even following the reﬁnements, there were several hundred relevant references
identiﬁed. The main selection from these was to concentrate on papers published in the past ﬁve
years, with an emphasis on experimental studies of biological properties and on reviews of clinical
performance. Key papers published before this have been included where they provide information
on current practice and illustrate how the clinical use of titanium-based implants has evolved.
2. Titanium-Based Dental Implants
Since the introduction of titanium alloys for the purpose around 1981, there has been a marked
increase in the use of dental implants to replace lost teeth in patients [
]. The most common reason
for tooth loss in adults is periodontal disease, though other causes, such as trauma and developmental
defects, may also lead to it [
]. Modern titanium-based dental implants have high success rates and are
only rarely associated with complications or failure .
Implants involve the use of a metal support that is in direct contact with the bone. Titanium is used
in alloys to fabricate dental implants due to its good mechanical properties, low density (4.5 g/cm
and good bone-contact biocompatibility. The main alloy used is so-called commercially pure titanium,
]. This metal is available in four grades numbered 1 to 4, according to the purity and the
processing oxygen content [
]. These grades diﬀer in corrosion resistance, ductility and strength, and it
is grade 4 cp-Ti, with the highest oxygen content (around 0.4%) and best overall mechanical strength
Prosthesis 2020,2, 100–116; doi:10.3390/prosthesis2020011 www.mdpi.com/journal/prosthesis
(see Table 1), that is most widely used for dental implants [
]. There is also the alloy Ti-6Al-4V,
sometimes called grade 5 titanium. Its composition is also shown in Table 1, where it can be seen that
the numbers in the formula refer to the approximate percentage composition by mass.
Grade 5 titanium is widely used in orthopaedics [
]. This is because of its superior strength
and lower Young’s modulus. However, it may also be used in dentistry, and the use of this alloy
has been shown to be acceptable biologically [
]. However, this alloy releases both aluminium and
], both of which are capable of causing biological problems. Aluminium interferes with
bone mineralization [
], leading to structural deﬁciencies, and vanadium is both cytotoxic and capable
of causing type IV (allergic) reactions [
]. To have these adverse eﬀects, they both need to be present
in the tissues at reasonable concentrations, and levels released from this alloy are well below those
needed to produce toxic eﬀects [
]. Amounts released are also below the average nutritional uptake
of these ions. Studies have conﬁrmed that this alloy will undergo satisfactory osseointegration [
especially when treated to enhance the oxide layer on the surface .
Table 1. Composition and properties of titanium alloys used as implants.
cpTi Grade 1 cpTi Grade 2 cpTi Grade 3 cpTi Grade 4 Ti6Al4V
Titanium ca 99% ca 99% ca 99% ca 99% 90%
Oxygen 0.18% 0.25% 0.35% 0.4% 0.2% max
Iron 0.2% 0.2% 0.2% 0.3% 0.25%
Nitrogen 0.03% 0.03% 0.05% 0.05% -
Hydrogen 0.15% 0.15% 0.15% 0.15% -
Carbon 0.1% 0.1% 0.1% 0.1% -
UTS/MPa 240 340 450 550 900
strength/MPa 170 275 380 480 850
failure/%25 20 18 15 10
The design of modern implants usually involves a screw thread through which the metal alloy
component becomes anchored within the bone of the mandible or maxilla. A smooth section of metal
protrudes through the soft tissue of the gingiva and supports the artiﬁcial tooth, which is typically
made from a ceramic material [
]. Partly as a result of this design, care has to be taken in selecting
the patient to receive an implant. There has to be enough bone in the aﬀected part of the mandible or
maxilla to secure and support the implant [
], and the site must also have a good supply of blood.
This means that the patient must be free of circulatory disorders, and should also be a non-smoker.
This latter factor is important because tobacco smoke has the eﬀect of making the blood capillaries
to contract, causing them to reduce the blood supply to the soft tissues [
]. Lastly, patients have to
maintain good levels of oral hygiene. This is to reduce the possibility of infection in the tissues adjacent
to the implant .
When implants are used in dentistry, they should be handled carefully to make sure that they do
not become contaminated. The surfaces should be kept scrupulously clean and, in order to achieve this,
precautions are advised, such as manipulating the implant with titanium-tipped forceps and avoiding
touching any of the surfaces [
]. Despite these precautions, surface analysis using X-ray photoelectron
spectroscopy (XPS) and time-of-ﬂight secondary ion mass spectrometry (ToF SIMS) has shown that
surfaces attract considerable amounts of contamination during handling [
]. This contamination is
typically organic, and shows high levels of carbon with some oxygen. Detecting titanium in these
surfaces was often not possible [
]. However, despite this, the long-term integrity of titanium implants
and their ability to osseointegrate are good. Survival rates of at least 89% over 10 years have been
reported, and ﬁgures have typically exceeded this ﬁgure by considerable amounts. These studies have
involved several hundred implants, with survival rates in the range 97–99% [
] (Table 2) showing
just how successful these devices are.
Table 2. Recent clinical outcomes of titanium-based dental implants.
Follow-Up Time/Years Pretreatment Survival Rate/% Reference
10 Sandblast and acid-etch 98.8 
10 Sandblast and acid-etch 99.7 
20 Plasma-sprayed with Ti 89.5 
10 Anodised 96.5 
9–12 Oxidised 97.1 
Another possible source of contamination that should be considered is bacterial contamination
during surgical placement of the dental implant [
]. This type of contamination can occur when
bacteria that are present naturally within the oral tissues colonise the sub-gingival surface of the
implant. This may then lead to infection and impairment of the healing process, with the process
of osseointegration being compromised [
]. A systematic review [
] considered this topic and
addressed the question of whether such contamination inﬂuences the success of dental implants to any
great extent, but concluded that there was insuﬃcient evidence to draw ﬁrm conclusions.
2.1. Titanium and its Alloys
Titanium is a transition metal that is able to form solid solutions with elements with similarly
sized atoms. In the solid state, it has hexagonal close packed geometry up to 882.5
C, known as the
structure. Above this temperature, solid titanium changes to a body centred cubic form known as the
structure, until it melts at 1688
]. In alloys, titanium occurs in a variety of forms, which can
, or combinations of the two [
]. The alloying elements with titanium are either
-stabilisers, such aluminium, or
-stabilisers, such as vanadium, iron, nickel and cobalt. Oxygen is an
-stabiliser. There are also a few metallic elements, such as zirconium, which have no inﬂuence on the
stability of either the phases.
In making implants, titanium alloys that are either completely or mainly
are preferred, because
they have superior corrosion resistance. The processing conditions can be selected to favour the
micro-structure, and this also aﬀects the mechanical properties (strength, ductility, fatigue resistance
and fracture toughness). Data on phase structures of titanium alloys and their physical properties are
given in Table 3.
Table 3. Properties of alloys of titanium for dental implants.
Alloy Micro-Structure Elastic Modulus/GPa Yield Strength/MPa Density/g cm−3
cpTi Grade 1 α102 170 4.5
cpTi Grade 2 α102 275 4.5
cpTi Grade 3 α102 380 4.5
cpTi Grade 4 α104 483 4.5
Ti-6A1-4V α+β113 795 4.4
2.2. Surface Chemistry
For both of the main alloys used to make implantable devices, namely commercially pure titanium,
cpTi, and Ti-6A1-4V, the surfaces are mainly composed of the oxide TiO
]. This oxide layer is
4–6 nm thick and also contains hydroxyl groups in addition to the oxide. The exact composition of
the surface is important in promoting the adhesion of osteoblasts and the oxide layer tends to have
favourable biological properties. However, the body still recognizes it as a foreign body, so that under
some circumstances it may cause ﬁbrosis to develop around the implant .
The detailed structure of the TiO
ﬁlm on titanium surfaces varies with the composition of
the alloy, and also with its processing history (see Table 4). Titanium implants usually have their
surfaces modiﬁed after their initial fabrication in order to ensure that oxidation is uniform and that
any contamination is removed [
]. The resulting surfaces have improved biological characteristics,
and promote the processes of cell adhesion and proliferation, both of which contribute to bone
Table 4. Possible surface treatments of titanium alloy implants.
Treatment type Surface Change Eﬀect
Machining Alter surface roughness. Cleans surface.
Grinding Improves adhesion
Acid treatment Modiﬁes oxide layer. Improves biocompatibility in all cases.
Alkali treatment Forms sodium titanate gel. Improves biocompatibility in all cases.
Hydrogen peroxide Dense inner oxide layer,
porous outer layer.
Anodic oxidation Increase thickness of TiO2
Plasma spray Deposits coating such as
Flame spray Deposits coating such as
Improves wear and corrosion resistance.
Ion beam implantation Modiﬁes surface composition. Enhances biological properties.
The surface of the alloy Ti-6A1-4V has quite a diﬀerent composition from those of the various
grades of cpTi [
]. As well as TiO
, this alloy contains both aluminium and vanadium in the surface
layers, usually as the appropriate metal oxides. This alters the metal–cell interactions, and is why
dental implants are more often made from cpTi.
The surface ﬁnish and roughness are also important features of titanium implants because they
inﬂuence the quality of the interaction with the bone. Surface roughness can be quantiﬁed by the
, the arithmetic mean of the roughness area from the mean plane, and S
, the density of peaks
per unit of area [
]. Surfaces of implants can be divided into four diﬀerent categories, depending
on the surface roughness based on the value of S
as follows: smooth (S
m); moderately rough (S
m); rough (S
In general, it is moderately rough surfaces that give the best results [34,35].
3. Biocompatibility of Titanium for Dental Implants
Corrosion behaviour is one of the most important factors that inﬂuence the biocompatibility of
metal implants. This is because the metal ions that corrosion liberates can cause various adverse eﬀects.
These can be both to the tissue immediately surrounding the implant and systemically, where there
may be allergic reactions. The latter, so called type IV reactions, do not depend on the dose, so are not
aﬀected by the rate of corrosion. They occur simply because corrosion causes metal ions to be released.
On the other hand, tissue reactions adjacent to the implant do depend on the dose, so that in
turn, they are aﬀected by the rate of corrosion. Titanium alloys have good corrosion resistance [
though this may be altered by the presence of proteins such as albumin, and consequently there can be
an increase in the amount of titanium released into the tissues [
]. Evaluating how much titanium
might be released and how damaging it might be is diﬃcult, because a number of diﬀerent animal
models have been used in the published studies, and also diﬀerent approaches to implantation and
implant retrieval have been used. In some animals, e.g., baboons and rabbits, titanium levels in the
tissues did not change when implants were present [
], whereas in other animals, e.g., rats, elevated
concentrations of titanium were found in the spleen and there was observable degeneration of the
The two most widely used titanium alloys, cpTi and Ti-6A1-4V can both readily osseointegrate.
Osseointegration is considered to occur when direct contact develops between the living bone and the
metal, without any intervening layer of ﬁbrous capsule. Both cpTi and Ti-6A1-4V are bioactive and
able to promote the formation of bone in direct contact with the metal surface. This is diﬀerent from
the biomedical alloys 316L stainless steel and cobalt-chromium, where living bone is unable to make
close contact with the metal surface.
The interfacial zone between the titanium alloy implant and living bone is critical in the
development of osseointegration. This region, which is thin (20–50 nm), is the region into which
growth factors are released from the bone cells, and this initiates the steps that result in bone
]. The initial step is deposition of proteins from the blood plasma onto the surface
oxide layer. This is followed by the formation of a ﬁbrin matrix, a structure that acts as a scaﬀold
for osteoblasts (the bone-forming cells) [
]. Supported in this way, the osteoblasts lay down bone,
which expands to ﬁll the interfacial region, so that it grows right up against the implant surface,
causing the implant to become osseointegrated. The important eﬀect of proper osseointegration is that
the implant is held rigidly, unlike the case where ﬁbrous capsule forms, and in dentistry this provides
a ﬁrm anchor for the prosthetic device.
The oxide layer on the surface plays a major role in the success of osseointegration. Thicker and
rougher oxide coatings encourage osseointegration to occur reliably and quickly, at least over the
shorter term [
]. The oxide coating also has the eﬀect of passivating the metal, so that corrosion is
inhibited and the release of titanium ions is minimized .
Cells of various types interact with the surfaces of titanium alloys. These alloys have surfaces
with the appropriate surface energy and charge, and the ﬁrst thing they do is to attract a layer of
]. A sequence of proteins is deposited, eventually leading to the deposition of extracellular
matrix proteins [
], and these stimulate the osteoblasts, which then become attached [
]. As has
already been mentioned, cells prefer rough, porous surfaces with an irregular morphology [
of the type that can be readily produced on implantable devices.
When dental implants are used, titanium levels in the blood [
] and the serum [
] are raised.
The increases are minor but signiﬁcant, and indicate that titanium is leached from these devices.
Entering the blood stream indicates that the titanium released is capable of being transported round
the whole body. However, in most patients, it has no toxic eﬀects on any of the body’s tissues [
a very small number, there may be adverse systemic eﬀects in the form of type IV reactions [
However, these are very rare and aﬀect only a very small number of patients. In most patients, titanium
is completely acceptable within the body and its presence causes no adverse eﬀects.
The widely used alloys cpTi and Ti-6Al-4V have excellent properties for use as dental implants.
There has been discussion in the literature as to which is better for use as dental implants [
cpTi is slightly favoured [
], but results of
studies have usually found that Ti-6Al-4V is superior.
What can be said of both alloys is that they undergo osseointegration and are highly biocompatible
with bone and oral tissues. They show minimal corrosion and cause few systematic eﬀects in a small
minority of patients. Biomechanically they are ﬁt for purpose and clinical survival rates are high over
many years of service. Consequently, the scope for improving them is slight. Nevertheless, there has
been some interest in developing new alloys for use as dental implants. The main approach has been to
eliminate the elements with the potential to cause harm biologically, mainly vanadium, and to reduce
the modulus so that it more closely matches that of bone [
]. The various approaches that have been
tried are considered in the remaining sections of this paper.
In order for an alloy to be considered biocompatible and for it to undergo osseointegration, it must
be tested in a variety of ways. One important preliminary test is for cytotoxicity. Like most metals,
titanium alloys in the bulk are not toxic, but when they corrode and form ions, or wear and generate
particles, they may become so [
]. In order to measure the cytotoxicity of metal ions or wear debris,
the standard method is the MTT assay, as described in the appropriate International Standard for the
biological evaluation of medical devices .
The test procedure involves a colorimetric test for mitochondrial activity of cultured cells using
the reagent MTT (3-(4,5-dimethylthiazol-2-yl diphenyltetrazolium bromide). When cells have active
mitochondria, they reduce MTT to a formazan that is both insoluble and strongly coloured [
The colour that develops, a deep purple, has a maximum absorbance at a wavelength of 570 nm and
measuring the absorbance at this wavelength enables the number of viable cells in a sample to be
quantiﬁed directly [56,57].
MTT assays are typically carried out in 96-well plates, which allows high throughput. The reagent is
dissolved in physiologically balanced solutions and added to cells in culture, typically at concentrations
in the range 0.2 to 0.5 mg/cm
. They are incubated for short periods of time (1–4 hours), then the
amount of the purple formazan produced is determined from absorbance measurements at 570 nm in
a calibrated colorimeter. Healthy cells with high mitochondrial activity produce the deepest purple
Testing in this way has been carried out on numerous titanium alloys in order to determine their
]. For example, Ti-6Al-4V has been shown to have cytotoxicity comparable
to that of pure titanium metal, despite the presence of both aluminium and vanadium [
Other alloying elements have also been shown to be acceptable using the MTT assay, including iron [
], niobium [
], zirconium [
] and tantalum [
]. Copper, by contrast, has been
found to increase the cytotoxicity markedly [
]. Studies have conﬁrmed that low cytotoxicity correlates
with cells being able to adhere to metal surfaces and remain functional [
]. Low cytotoxicity is thus
the foundation of the other desirable biological properties of titanium alloys, namely biocompatibility
4. Binary Alloys of Titanium
A large number of metals have been alloyed with titanium, typically as the minor component,
to prepare alloys for possible use as dental implants. These include niobium [
], silver [
], manganese [
] and zirconium [
]. Some alloying elements, such as silver or
] probably reduce the biocompatibility of the alloy. This is because they are likely to
release either silver or chromium, both of which are known to have adverse biological eﬀects [
On the other hand, several of the elements used, such as niobium [
] and zirconium [
], are benign in
terms of their biological eﬀects, so the resulting alloys are more promising for use as implant materials.
A considerable amount of work has been done on binary alloys of titanium with zirconium.
These have varied widely in composition, from 10% by mass zirconium [
], to up to 50% by mass
] and, in one study, 70% by mass zirconium [
]. Zirconium has a number of advantages
as alloying metal for this application. It readily forms alloys with titanium, and it strongly resists
], which means that it releases only trace amounts of metal ions into the body. Despite this,
Ti-Zr alloys show inferior osseointegration with living bone [
]. On the other hand, studies aimed
speciﬁcally at dental applications have shown the alloys to have mechanical properties comparable
with cpTi [
], and, with suitable surface preparation, good biocompatibility and improved osteoblast
adhesion compared with cpTi [
]. Both of these ﬁndings suggest that Ti-Zr alloys may have some
advantages when used for dental implants.
Niobium has also been studied in binary alloys with titanium [
], though it has been more widely
used in ternary alloys, such as Ti-6Al-7Nb [
]. Binary alloys containing minor amounts of niobium
(less than 10% by mass) have been found to have good mechanical properties. Their hardness, yield
strengths and tensile strengths typically exceed those of cpTi [
]. There is also evidence that their
corrosion behaviour is improved [
]. Despite this improvement, experimental studies have shown
that human ﬁbroblasts grow slower and less extensively in Ti-Nb alloys than on cpTi .
Manganese is an element that is generally acceptable biologically [
], and for that reason it has
been studied in binary alloys with titanium. Levels have been relatively low, i.e., 8% or 12% by
mass, and the eﬀects have been beneﬁcial. Hardness and density both increase when manganese is
]. Cell adhesion appears to be enhanced in the alloy [
], but cell viability adjacent to these
alloys was slightly inferior that that around a cpTi implant .
The noble metals silver [
], gold [
], platinum and palladium [
] have been used to prepare
binary biomedical alloys with titanium. Not surprisingly, these alloys were all found to have improved
corrosion resistance compared with cpTi, so might be expected to show superior biocompatibility
with bone and soft tissues [
]. However, this has only been conﬁrmed experimentally for the
Ti-Ag system [
]. Such alloys are inevitably expensive [
], and it is doubtful whether the marginal
improvement in corrosion resistance justiﬁes their high cost.
There have been some studies reported on binary alloys of indium with titanium [
Like zirconium, indium has also been used in multi-component alloys, such as Ti-In-Nb-Ta, where the
alloy showed good bioactivity [
]. In binary alloys, indium imparted increased strength and also
corrosion resistance that was at least as good as cpTi [
]. This, in turn, led to the alloy having good
biocompatibility in cell cultures.
So far, these studies of binary alloys suggest that there are several possible pairings with titanium
that are less susceptible to corrosion, and because of this, show greater biocompatibility with cells.
However, the only binary alloy that has really been oﬀered substantial improvements so far is Ti-Zr,
and there are ongoing studies on this material as a possible alloy for fabricating dental implants.
5. Multi-Component Alloys of Titanium
A range of alloys containing at least three metals has been studied as possible implant materials,
including for dentistry. They are listed in Table 5. The additional components are typically transition
metals, though tin has also been included in a few experimental studies. In some instances, changes in
composition resulted in the inclusion of additional amounts of oxygen [
], though the oxygen
concentration has not typically been aﬀected by changes in metal composition.
Table 5. Multi-component alloys studied as implant materials.
Composition Reference Reference
Okazaki et al, Biomaterials,1998,19, 1197. 
Ti-15Zr-4Nb-4Ta-4Mo Okazaki et al, Biomaterials,1998,19, 1197. 
Ti-16Nb-13Ta-4Mo Niinomi, et al, Mater. Sci. Eng. A., 1999,263, 193. 
Ti-15Sn-4Nb-2Ta-0.2Pd Okazaki et al, Biomaterials,1998,19, 1197. 
Ti-15Sn-4Nb-0.2Pd-0.2O Okazaki et al, Biomaterials,1998,19, 1197. 
Ti-15Zr-10Cr Wang et al, Mater. Sci. Eng. C., 2015,51, 148. 
Ti-13Nb-13Zr Correa et al, Mater. Sci. Eng. C., 2014,34, 354. 
Ti-29Nb-13Ta-4Mo Niinomi et al, Mater. Sci. Eng. A., 1999,263, 193. 
Ti-29Nb-13Ta-6Sn Niinomi et al, Mater. Sci. Eng. A., 1999,263, 193. 
Ti-29Nb-13Ta-2Sn Niinomi et al, Mater. Sci. Eng. A., 1999,263, 193. 
Ti-19Zr-10Nb-1Fe Xue et al, Mater. Sci. Eng. C., 2015,50, 179–186. 
Raducanu et al, J. Mech. Behav. Biomed. Mater.,
Ti-29Nb-13Ta-7Zr Correa et al, Mater. Sci. Eng. C., 2014,34, 354. 
Raducanu et al, J. Mech. Behav. Biomed. Mater.,
Elements, such as tin, iron and palladium, have been used only in a relatively few studies, whereas
others, such as zirconium, niobium and tantalum, have been studied by several groups of workers
and results with them appear in a number of publications. Niobium and tantalum both stabilize the
phase of titanium [
], so their presence eﬀectively replaces vanadium in Ti-6Al-4V and in the
case of either metal, does so with an improvement in the biological acceptability of the resulting alloy.
Alloys that are fabricated with niobium and/or tantalum contain both the
phases. The presence
phase is particularly desirable in biomedical grades of titanium because it confers low elastic
modulus and increased corrosion resistance [93,96], both of which result in superior performance.
One multi-component alloy of titanium with niobium that has been widely studied for bone-contact
applications is Ti-6Al-7Nb. In particular, it has become increasingly used to fabricate dental
. It is an
alloy and was originally developed for orthopaedics, and has
superior mechanical properties compared with cpTi [
]. It is also resistant to corrosion [
when corrosion does occur, its biological properties are acceptable, mainly because of the absence of
In terms of the biological responses it evokes, Ti-6Al-7Nb resembles cpTi. Human gingival
ﬁbroblasts have been found to adhere, spread and proliferate to similar extents on both alloys [
Short-term implantation of Ti-6Al-7Nb has been shown to provoke a brief inﬂammatory response
that was similar to that associated with cpTi, but subsequently to lead to highly satisfactory biological
]. There is also some evidence that Ti-6Al-7Nb promotes better spreading of
osteoblast-like cells than cpTi [
] and that its ability to undergo osseointegration in animal models
(dogs) is good .
Electrochemical studies have been carried out to determine the corrosion behaviour of Ti-6Al-7Nb.
In Hank’s solution, a composition designed to mimic physiological ﬂuids from the body, Ti-6Al-7Nb
showed high corrosion resistance and good stability [
]. Mechanical strength and wear resistance
were also found to be good when Ti-6Al-7Nb was prepared as castings [
], which conﬁrmed the
promise of this alloy for use as dental prostheses.
Overall, Ti-6Al-7Nb has been shown to have particularly good properties, both physical and
biological, for use in dentistry. However, it does not seem to be particularly widely used for this
purpose, as far as it is possible to judge from the literature. Most studies concern cpTi, with some
considering Ti-6Al-4V, and relatively few explicitly state that they use the alloy Ti-6Al-7Nb. Given the
experimental results that implants made from this alloy have shown, this may change in the future.
6. Surface Modiﬁcation of Titanium Alloys
As has been described already, the surface of the implant is critical for ensuring the necessary
osseointegration of dental implants. As well as relying on the natural oxide coating that is found on
titanium alloy surfaces, various approaches to altering these surfaces have been studied. These range
from roughening, through either acid or alkaline treatment, typically being followed by heating, to
coating with an inorganic material such as hydroxyapatite or diamond-like carbon. These approaches
will now be considered brieﬂy. As with much of the work on titanium alloys, many of the studies have
been aimed at improving materials for orthopaedics, and modifying surfaces speciﬁcally for dental
implants has been studied much less.
Roughening the surface by some additional processing step has been found to be eﬀective in
improving the ability of titanium alloys to undergo osseointegration. This roughening also leads to
higher survival rates for dental implants [
]. For example, one study compared the survival rates
of implants with rough and smooth surfaces, and showed that the survival rates at 20 to 27 months
was 98% for the rough surface but only 81% for the smooth one [
]. The roughening process has
been shown to alter the surface energy, and this improves the deposition of protein, which in turn
enhances the attachment of cells and improves osseointegration of the implant .
Surfaces can be roughened by various methods. One involves blasting with particulates,
possibly sand, but also alumina, corundum of hydroxyapatite [
]. Another involves etching with
mineral acids such as aqueous HCl and H
of appropriate concentrations [
]. These substances
can be used as the only treatment, or can be combined with sandblasting to produce surfaces of
diﬀering degrees of roughness [
]. The combined roughening approach has been shown to be
especially successful in producing surfaces that develop close early contact with bone following
], though over the longer term (six weeks or more) there was no advantage in using
this technique, and bone contact with the implant surface was no longer improved by it having
Acid-etching to roughen surfaces is not the only chemical method that has been used. Alkaline
treatment has also been used to alter surfaces, though this tends not alter surface roughness but to
aﬀect surface charge. As an example, it has been found that treatment of titanium alloy with strongly
concentrated NaOH solution results in a sodium titanate surface that interacts more actively with bone
and more readily promotes growth [
]. Alkaline treatment results in a negatively charged surface that
rapidly adsorbs calcium ions from body ﬂuids [
studies using simulated body ﬂuid
(SBF) have shown that the initial adsorption of Ca
ions is quickly followed by deposition of phosphate
ions and the eventual formation of hydroxyapatite [
]. The sequential nature of this deposition
process has been conﬁrmed by X-ray photoelectron spectroscopy [
]. However, despite this
success, such alkaline treatments have mainly been considered for orthopaedic devices [
than for dental implants.
One other method that has been widely studied for modifying implant surfaces is anodic
oxidation. This is an accelerated electrochemical process that leads to the formation of a substantial
oxide coating on the metal surface [
]. The development of such a thick oxide coating on titanium
implants may improve corrosion resistance [
], as well as enhancing the bonding of bone cells to the
A coating formed by anodic oxidation depends on a number of features of the electrochemical
process, including anode voltage and the composition of the electrolyte solution. High voltages tend to
produce thicker and more porous oxide coatings than lower voltages [
]. Various types of electrolyte
solution can be used, such as solutions of sulfuric acid, phosphoric acid or ethanoic acid, as well
as neutral salts, or even alkaline solutions, such as aqueous calcium or sodium hydroxide [
and a variety of thicknesses and crystal structures of titanium dioxide have been produced. Despite
these successes, it is not clear to what extent such approaches are used on practical implant devices.
Indeed, there have been no reports on the long-term eﬀects of these observed improvements in cell
attachment and corrosion resistance, and with the present level of knowledge, it is not clear that
surfaces prepared in this way oﬀer any clinical advantages over oxide ﬁnishes that occur naturally on
titanium alloy implants.
The most obvious substance to use to coat implants is hydroxyapatite, and this has been used
successfully in orthopaedics to develop so-called cementless prostheses [
]. Hydroxyapatite coating
has also been used for dental implants [
] with the aim of improving the rate of osseointegration [
The hope is to shorten treatment times, especially for patients whose bone quality is poor [133,134].
Early results with coatings applied to dental implants in the 1990s were not good for various reasons,
including detachment of the hydroxyapatite coating and dissolution of the detached HA [
However, recently coating methods have been improved, and techniques such as ion-sputtering or
thermal plasma treatment have been used [
]. This has resulted in more durable coatings that
adhere better to the titanium substrate and therefore have greater promise for clinical use. This has led
to renewed interest in coating dental implants. The demands of speciﬁc locations suggest that coated
implants might be necessary in order to ensure optimum clinical results. For example, hydroxyapatite
screw implants have been recommended for the anterior maxilla and the posterior mandible [
However, uncertainty remains about the long-term durability of these coatings remains, and although
research is continuing on hydroxyapatite-coated dental prostheses, they are used on only a minority of
clinical implants in current practice [
]. The high bioactivity of titanium alloy surfaces, together with
the ability to undergo osseointegration reliably means that any improvement from hydroxyapatite
coatings would have to be substantial, and current coatings have not yet shown the necessary levels
Another material that has been used to coat dental implants, at least for experimental study,
is diamond-like carbon (DLC) [
]. This is an amorphous material that has high inherent
biocompatibility with bone, and has been applied using chemical vapour deposition onto heated
cpTi abutment screws [
]. The application technique can be varied somewhat, and can include
]. It should ideally include the deposition of an intermediate layer, such as
amorphous silicon, to promote adhesion of DLC to the substrate [
]. The aim has been to produce
surfaces of improved corrosion resistance and enhanced biocompatibility, and there is experimental
evidence that success with these aspects can be achieved
]. However, despite this
promise, this approach has not yet had any impact on clinical practice, and DLC-coated dental implants
are not yet being used in patients.
This paper has described the reasons that titanium alloys are the materials of choice for the
fabrication of dental implants. The principal alloys in practical use are commercially pure titanium and
Ti-6Al-4V. The mechanical properties of the latter are better, but the slight concern over the biological
eﬀects of the very minor amounts of aluminium and vanadium that they release means that cpTi is the
more widely used of the two. Despite these concerns, there is a large amount of experimental evidence
to show that both alloys have good bioactivity and the ability to osseointegrate. Additionally, there are
few, if any, accounts of adverse eﬀects arising from release of aluminium and/or vanadium from dental
implants, probably because amounts released are so low.
The result of the excellent biological and mechanical properties of titanium alloys is that success
rates with dental implants made of these materials are very high. Various studies are described which
show that failure rates over considerable time periods are extremely low. Depending on the details
of the study and the materials used, at least 89% and typically 97–99% of implants survive for over
10 years. Given these results, the scope for improving either the materials or the clinical procedures
is limited. For this reason, the two well-established alloys of titanium continue to be used for the
overwhelming majority of implants used in dentistry, and this use seems likely to continue for the
Funding: This work received no external funding.
Conﬂicts of Interest: The author declares no conﬂict of interest.
Hong, D.G.K.; Oh, J.-H. Recent advances in dental implants. Maxillofac. Plast. Reconstr. Surg.
Shemtov-Yona, K.; Rittel, D. An overview of the mechanical integrity of dental implants. Biomed. Res. Int.
2015,2015. [CrossRef] [PubMed]
McCracken, M. Dental implant materials: Commercially pure titanium and titanium alloys. J. Prosthodont.
1999,8, 40–43. [CrossRef]
Liu, X.; Chen, S.; Tsoi, J.K.H.; Matinlinna, J.K. Binary titanium alloys as dental implant Materials—A review.
Regen. Biomater. 2017,4, 315–323. [CrossRef] [PubMed]
Zhang, L.; Chen, L.-Y. A review on biomedical titanium alloys: Recent progress and prospect. Adv. Eng. Mater.
Niiomi, M. Mechanical biocompatibilities of titanium alloys for biomedical applications. J. Mech. Behav.
Biomed. Mater. 2008,1, 30–42. [CrossRef]
Elias, C.N.; Fernandes, D.J.; De Souza, F.M.; Monteiro, E.D.S.; De Biasi, R.S. Mechanical and clinical properties
of titanium and Titanium-Based alloys (Ti G2, Ti G4 cold worked nanostructured and Ti G5) for biomedical
applications. J. Mater. Res. Technol. 2019,8, 1060–1069. [CrossRef]
Klein, G.L. Aluminium toxicity to bone: A Multi-System eﬀect? Osteoporos. Sarcopenia
,5, 2–5. [CrossRef]
Thyssen, J.; Jakobsen, S.S.; Engkilde, K.; Johansen, J.D.; Søballe, K.; Menn
, T. The association between metal
allergy, total hip arthroplasty, and revision. Acta Orthop. 2009,80, 646–652. [CrossRef]
n, O.G.; De Arriba, C.C.; Alobera, M.A.; Aguado-Henche, S.; Escudero, M.; Garc
Osseointegration of TI6Al4V dental implants modiﬁed by thermal oxidation in osteoporotic rabbits. Int. J.
Implant Dent. 2016,2, 18. [CrossRef]
Saini, M.; Singh, Y.; Arora, P.; Arora, V.; Jain, K. Implant biomaterials: A comprehensive review. World J.
Clin. Cases 2015,3, 52–57. [CrossRef]
Jorge, J.R.P.; Bar
o, V.A.R.; Delben, J.; Faverani, L.P.; Queiroz, T.P.; Assunç
o, W.G. Titanium in dentistry:
Historical development, state of the art and future perspectives. J. Indian Prosthodont. Soc.
Sidambe, A.T. Biocompatibility of advanced manufactured titanium Implants—A review. Materials
Naderi, N.J.; Semyari, H.; Elahinia, Z. The impact of smoking on gingiva: A histopathological study.
Iran. J. Pathol. 2015,10, 214–220.
Pye, A.; Lockhart, D.; Dawson, M.; Murray, C.; Smith, A. A review of dental implants and infection.
J. Hosp. Infect. 2009,72, 104–110. [CrossRef]
Nicholson, J.W. The Chemistry of Medical and Dental Materials, 4th ed.; RSC: Cambridge, UK, 2002; pp. 107–147.
Ameen, A.P.; Short, R.D.; Douglas, C.W.I.; Johns, R.; Ballet, B. A critical investigation of some of the procedures
employed in the surgical use of titanium. J. Mater. Sci. Mater. Electron. 1996,7, 195–199. [CrossRef]
Buser, D.; Janner, S.F.M.; Wittneben, J.-G.; Bragger, U.; Ramseier, C.A.; Salvi, G.E. 10-Year survival and success
rates of 511 titanium implants with a sandblasted and Acid-Etched surface: A retrospective study in 303
partially edentulous patients. Clin. Implant Dent. Relat. Res. 2012,14, 839–851. [CrossRef]
Van Velzen, F.J.J.; Ofec, R.; Schulten, E.A.J.M.; Bruggenkate, C.M.T. 10-Year survival rate and the incidence of
Peri-Implant disease of 374 titanium dental implants with a SLA surface: A prospective cohort study in 177
fully and partially edentulous patients. Clin. Oral Implant Res. 2014,26, 1121–1128. [CrossRef]
Chappuis, V.; Buser, R.; Bragger, U.; Bornstein, M.M.; Salvi, G.E.; Buser, D. Long-Term outcomes of dental
implants with a titanium Plasma-Sprayed surface: A 20-Year prospective case series study in partially
edentulous patients. Clin. Implant Dent. Relat. Res. 2013,15, 780–790. [CrossRef]
Degidi, M.; Nardi, D.; Piattelli, A. 10-Year Follow-Up of immediately loaded implants with tiunite porous
anodized surface. Clin. Implant Dent. Relat. Res. 2012,14, 828–838. [CrossRef]
Mozzati, M.; Gallesio, G.; Del Fabbro, M. Long-Term (9–12 years) outcomes of titanium implants with an
oxidized surface: A retrospective investigation on 209 implants. J. Oral Implant
,41, 437–443. [CrossRef]
Johansson, K.; Jimbo, R.; Östlund, P.; Tranæus, S.; Becktor, J. Eﬀects of bacterial contamination on dental
implants during surgery. Implant Dent. 2017,26, 778–789. [CrossRef]
Zhao, B.; Van Der Mei, H.C.; Rustema-Abbing, M.; Busscher, H.J.; Ren, Y. Osteoblast integration of dental
implant materials after challenge by Sub-Gingival pathogens: A Co-Culture study
.Int. J. Oral Sci.
2015,7, 250–258. [CrossRef]
Niinomi, M.; Nakai, M. Titanium-Based biomaterials for preventing stress shielding between implant devices
and bone. Int. J. Biomater. 2011,2011. [CrossRef] [PubMed]
Osman, R.B.; Swain, M.V. A critical review of dental implant materials with an emphasis on titanium versus
zirconium. Materials 2015,8, 932–958. [CrossRef]
Eﬀah, E.A.; Bianco, P.D.; Ducheyne, P. Crystal structure of the surface oxide layer on titanium and its changes
arising from immersion. J. Biomed. Mater. Res. 1995,29, 73–80. [CrossRef]
Sittig, C.; Textor, M.; Spencer, N.D.; Weiland, M.; Vallotton, P.-H. Surface characterization of implant materials
cpTi, Ti-6Al-7Nb and Ti-6Al-4V with diﬀerent pre-treatments. J. Mater. Sci. Mater. Med.
Al-Hashedi, A.A.; Laurenti, M.; Benhamon, V.; Tamimi, F. Decontamination of titanium implants using
physical methods. Clin. Oral Implants Res. 2017,28, 1013–1021. [CrossRef]
Juodzbalys, G.; Sapragonlene, M.; Wennerberg, A.; Baltrukonis, T. Titanium oral implant surface
micromorphology optimization. J. Oral Implantol. 2007,33, 177–185.
Hanawa, T. Titanium-tissue interface reaction and its control within surface treatment.
Front. Bioeng. Biotechnol.
2019,7, 170. [CrossRef]
Albrektsson, T.; Wennerberg, A. Oral implant surfaces: Part 1—Review focusing on topographic and chemical
properties of diﬀerent surfaces and
responses to them. Int. J. Prosthodont.
,17, 536–543. [PubMed]
Elias, C.N.; Meirelles, L. Improving osseointegration of dental implants. Expert Rev. Med Devices
Balshe, A.A.; Assad, D.A.; Eckert, S.E.; Koka, S.; Weaver, A.L. A retrospective study of the survival of
Smooth-And Rough-Surface dental implants. Int. J. Oral Maxillofac. Implants 2009,24, 1113–1118.
Wennerberg, A.; Albrektsson, T. On implant surfaces: A review of current knowledge and opinions. Int. J.
Oral Maxillofac. Implants 2010,25, 63–74.
Vora, H.D.; Rajamure, R.S.; Dahotre, S.N.; Ho, Y.-H.; Banerjee, R.; Dahotre, N.B. Integrated experimental and
theoretical approach for corrosion and wear evaluation of laser surface nitrided, Ti–6Al–4V biomaterial in
physiological solution. J. Mech. Behav. Biomed. Mater. 2014,37, 153–164. [CrossRef]
Yu, F.; Addison, O.; Davenport, A. A synergistic eﬀect of albumin and H 2 O 2 accelerates corrosion of
Ti6Al4V. Acta Biomater. 2015,26, 355–365. [CrossRef]
Rodriguez, D.; Gil, F.J.; Planell, J.A.; Jorge, E.; Alvarez, L.; Garcia, R.; Larrea, M.; Zapata, A. Titanium levels
in rats implanted with Ti-6Al-4V treated samples in the absence of wear. J. Mater. Sci. Mater. Med.
Apostu, D.; Lucaciu, O.; Lucaciu, G.D.O.; Crisan, B.; Crisan, L.; Baciut, M.; Onisor, F.; Baciut, G.; C
Bran, S. Systemic drugs that inﬂuence titanium implant osseointegration. Drug Metab. Rev.
Mavrogenis, A.F.; Dimitriou, R.; Parvizi, J.; Babis, G.C. Biology of implant osseointegration. J. Musculoskelet.
Neuronal Interact. 2009,9, 61–71. [PubMed]
Jemat, A.; Ghazali, M.J.; Razali, M.; Otsuka, Y. Surface modiﬁcations and their eﬀects on titanium dental
implants. BioMed Res. Int. 2015,10. [CrossRef]
John, A.A.; Jaganathan, S.K.; Supriyanto, E.; Manikandan, A. Surface modiﬁcation of titanium and its alloys
for the enhancement of osseointegration in orthopaedics. Curr. Sci. 2016,111, 1003–1015. [CrossRef]
Blumenthal, N.C.; Cosma, V. Inhibition of apatite formation by titanium and vanadium ions. J. Biomed.
Mater. Res. 1989,23, 13–22. [CrossRef] [PubMed]
Nuss, K.M.R.; von Rechenberg, B. Biocompatibility issues with modern implants in Bone—A review for
clinical orthopaedics. Open Orthop. J. 2008,2, 66–78. [CrossRef] [PubMed]
45. Sartoretto, S.C.; Alves, A.T.N.N.; Resende, R.F.B.; Calasans-Maia, J.A.; Granjeiro, J.M.; Calasans-Maia, M.D.
Early osseointegration driven by the surface chemistry and wettability of dental implants. J. Appl. Oral Sci.
2015,23, 279–287. [CrossRef]
Brangdon, C.R.; Jasty, M.; Greene, M.; Rubash, H.E.; Harris, W.H. Biologic ﬁxation of total hip implants:
Insghts gained from a series of canine studies. J. Bone Jt. Surg. 2004,86, 105–117. [CrossRef]
Temiz, M.; Dayi, E.; Saruhan, N. Evaluation of blood titanium levels and total bone contact area of dental
implants. Biomed. Res. Int. 2018,2018. [CrossRef]
Patton, M.S.; Lyon, T.D.B.; Ashcroft, G.P. Levels of systemic metal ions in patients with intramedullary nails.
Acta Orthop. 2008,79, 820–825. [CrossRef]
Nuevo-Ordoñez, Y.; Montes-Bay
n, M.; Blanco-Gonz
lez, E.; Paz-Aparicio, J.; Raimundez, J.D.; Tejerina, J.M.;
Peña, M.A.; Sanz-Medel, A. Titanium release in serum of patients with diﬀerent bone ﬁxation implants and
its interaction with serum biomolecules at physiological levels. Anal. Bioanal. Chem.
Kim, K.T.; Eo, M.Y.; Nguyen, T.T.H.; Kim, S.-M. General review of titanium toxicity. Int. J. Implant Dent.
5, 10. [CrossRef]
Pigatto, P.D.; Berti, E.; Spadari, F.; Bombeccari, G.P.; Guzzi, G. Photoletter to the editor: Exfoliative cheilitis
associated with titanium dental implants and mercury amalgam. J. Dermatol. Case Rep.
,5, 89–90. [CrossRef]
Shah, F.A.; Trobos, M.; Thomsen, P.; Palmquist, A. Commercially pure titanium (cp-Ti) versus titanium alloy
(Ti6Al4V) materials as bone anchored Implants–Is one truly better than the other? Mater. Sci. Eng. C
62, 960–966. [CrossRef] [PubMed]
Cordeiro, J.M.; Bar
o, V.A.R. Is there scientiﬁc evidence favoring the substitution of commercially pure
titanium with titanium alloys for the manufacture of dental implants? Mater. Sci. Eng. C
Hanawa, T. Evaluation of metallic biomaterials
.Sci. Technol. Adv. Mater.
,3, 289–295. [CrossRef]
International Organization for Standardization. Biological Evaluation of Medical Devices, Part 5: Tests for
Cytotoxicity; ISO10993-5; ISO: Geneva, Switzerland, 2009.
Berridge, M.; Tan, A.; McCoy, K.; Wang, R. The biochemical and cellular basis of cell proliferation assays that
use tetrazolium salts. Biochemica 1996,4, 14–19.
Marshall, N.J.; Goodwin, C.J.; Holt, S.J. A critical assessment of the use of microculture tetrazolium assays to
measure cell growth and function. Growth Regul. 1995,5, 69–84. [PubMed]
Koike, M.; Lockwood, P.E.; Wataha, J.C.; Okabe, T. Initial cytotoxicity of novel titanium alloys. J. Biomed.
Mater. Res. Part B Appl. Biomater. 2007,83, 327–331. [CrossRef] [PubMed]
Watanabe, I.; Wataha, J.C.; Lockwood, P.E.; Shimizu, H.; Cai, Z.; Okabe, T. Cytotoxicity of commercial and
novel binary titanium alloys with and without a Surface-Reaction layer. J. Oral Rehabil.
Oh, K.-T.; Kang, D.-K.; Choi, G.-S.; Kim, K.-N. Cytocompatibility and electrochemical properties of Ti–Au
alloys for biomedical applications. J. Biomed. Mater. Res. Part B Appl. Biomater.
,83, 320–326. [CrossRef]
Zhang, F.; Weidmann, A.; Nebe, J.B.; Beck, U.; Burkel, E. Preparation, microstructures, mechanical properties,
and cytocompatibility of TiMn alloys for biomedical applications. J. Biomed. Mater. Res. Part B Appl. Biomater.
2010,94, 406–413. [CrossRef]
Li, Y.; Wong, C.; Xiong, J.; Hodgson, P.; Wen, C. Cytotoxicity of titanium and titanium alloying elements.
J. Dent. Res. 2010,89, 493–497. [CrossRef]
Cremasco, A.; Messias, A.D.; Esposito, A.R.; deR Duek, E.A.; Caram, R. Eﬀects of alloying elements on
cytotoxic responses to titanium alloys. Mater. Sci. Eng. C. 2011,31, 833–839. [CrossRef]
Uzumaki, E.T.; Lambert, C.S.; Santos, A.R.J.; Zavaglia, C.A.C. Surface properties and cell behavior of
Diamond-Like carbon coatings produced by plasma immersion. Thin Sol. Film. 2006,515, 293–300. [CrossRef]
65. Lee, C.M.; Ju, C.P.; Lin, J.-H.C. Structure-Property relationship of cast Ti-Nb alloys. J. Oral Rehabil. 2002,29,
Kikuchi, M.; Takahashi, M.; Okuno, O. Mechanical properties and grindability of dental cast Ti-Nb alloys.
Dent. Mater. J. 2003,22, 328–342. [CrossRef]
Zhou, F.; Wang, B.L.; Qiu, K.; Lin, W.; Li, L.; Wang, Y.; Nie, F.; Zheng, Y. Microstructure, corrosion behavior
and cytotoxicity of Zr–Nb alloys for biomedical application. Mater. Sci. Eng. C
,32, 851–857. [CrossRef]
Oh, K.-T.; Shim, H.-M.; Kim, K.-N. Properties of Titanium-Silver alloys for dental application. J. Biomed.
Mater. Res. Part B Appl. Biomater. 2005,74, 649–658. [CrossRef]
Zhang, B.; Qiu, K.; Wang, B.L.; Li, L.; Zheng, Y. Surface characterization and cell response of binary Ti-Ag
alloys with CP Ti as material control. J. Mater. Sci. Technol. 2012,28, 779–784. [CrossRef]
Takahashi, M.; Kikuchi, M.; Okuno, O. Mechanical properties and grindability of experimental Ti-Au alloys.
Dent. Mater. J. 2004,23, 203–210. [CrossRef]
Zhang, F.; Weidmann, A.; Nebe, B.J.; Burkel, E. Preparation of TiMn alloy by mechanical alloying and spark
plasma sintering for biomedical applications. J. Phys. Conf. Ser. 2009,144, 012007. [CrossRef]
Ho, W.-F.; Chen, W.-K.; Wu, S.-C.; Hsu, H.-C. Structure, mechanical properties, and grindability of dental
Ti–Zr alloys. J. Mater. Sci. Mater. Electron. 2008,19, 3179–3186. [CrossRef]
Hsu, H.-C.; Wu, S.-C.; Hsu, S.-K.; Sung, Y.-C.; Ho, W.-F. Eﬀects of heat treatments on the structure and
mechanical properties of Zr–30Ti alloys. Mater. Charact. 2011,62, 157–163. [CrossRef]
Hsu, H.-C.; Wu, S.-C.; Sung, Y.-C.; Ho, W.-F. The structure and mechanical properties of as-cast Zr–Ti alloys.
J. Alloys Compd. 2009,488, 279–283. [CrossRef]
Hsu, H.-C.; Wu, S.-C.; Chiang, T.-Y.; Ho, W.-F. Structure and grindability of dental Ti–Cr alloys.
J. Alloys Compd.
2009,476, 817–825. [CrossRef]
Lansdown, A.B.G. A pharmacological and toxicological proﬁle of silver as an antimicrobial agent in medical
devices. Adv. Pharmacol. Sci. 2010,2010. [CrossRef]
Steinberg, J.; Shah, K.; Gartland, A.; Zeggini, E.; Wilkinson, J.M. Eﬀects of chronic cobalt and chromium
exposure after Metal-On-Metal hip resurfacing: An Epigenome-Wide association pilot study. J. Orthop. Res.
2017,35, 2323–2328. [CrossRef]
Ho, W.-F.; Cheng, C.-H.; Pan, C.-H.; Wu, S.-C.; Hsu, H.-C. Structure, mechanical properties and grindability
of dental Ti–10Zr–X alloys. Mater. Sci. Eng. C 2009,29, 36–43. [CrossRef]
Kobayashi, E.; Matsumoto, S.; Doi, H.; Yoneyama, T.; Hamanaka, H. Mechanical properties of the binary
titanium-zirconium alloys and their potential for biomedical materials. J. Biomed. Mater. Res.
943–950. [CrossRef] [PubMed]
study on biocompatibility and wear of zirconium and titanium. J. Stomatol. Soc. Jan.
60, 54–65. [CrossRef] [PubMed]
Gahlert, M.; Gudehus, T.; Eichorn, S.; Steinhauser, E.; Kniha, H.; Erhardt, W. Biomechanical and
histomorphometric comparison between zirconia implants with varying surface textures and a titanium
implant in the maxilla if miniature pigs. Clin. Oral Implants Res. 2007,18, 662–668. [CrossRef]
Wen, C.; Yamada, Y.; Hodgson, P. Fabrication of novel TiZr alloy foams for biomedical applications. Mater. Sci.
Eng. C 2006,26, 1439–1444. [CrossRef]
Sista, S.; Nouri, A.; Li, Y.; Wen, C.; Hodgson, P.D.; Pande, G. Cell biological responses of osteoblasts on
anodized nanotubular surface of a Titanium-Zirconium alloy. J. Biomed. Mater. Res. Part A
3416–3430. [CrossRef] [PubMed]
Falanga, A.; Laheurte, P.; Vahabi, H.; Tran, N.; Khamseh, S.; Saeidi, H.; Khodadadi, M.; Zarrintaj, P.; Saeb, M.R.;
Mozafari, M. Niobium-Treated titanium implants with improved cellular and molecular activities at the
Tissue-Implant interface. Materials 2019,12, 3861. [CrossRef] [PubMed]
Nicula, R.; Lüthen, F.; Stir, M.; Nebe, B.; Burkel, E. Spark plasma sintering synthesis of porous nanocrystalline
titanium alloys for biomedical applications. Biomol. Eng. 2007,24, 564–567. [CrossRef] [PubMed]
Nakagawa, M.; Matono, Y.; Matsuya, S.; Udoh, K.; Ishikawa, K. The eﬀect of Pt and Pd alloying additions on
the corrosion behavior of titanium in Fluoride-Containing environments. Biomaterials
Hwang, M.-J.; Park, E.-J.; Moon, W.-J.; Song, H.-J.; Park, Y.-J. Characterization of passive layers formed on
Ti–10wt% (Ag, Au, Pd, or Pt) binary alloys and their eﬀects on galvanic corrosion. Corros. Sci.
Takahashi, M.; Kikuchi, M.; Takada, Y.; Okuno, O.; Okabe, T. Corrosion behavior and microstructures of
experimental Ti-Au alloys. Dent. Mater. J. 2004,23, 109–116. [CrossRef]
Wang, Q.; Wang, Y.; Lin, J.; Zheng, Y. Development and properties of Ti–In binary alloys as dental biomaterials.
Mater. Sci. Eng. C 2013,33, 1601–1606. [CrossRef]
Han, M.-K.; Im, J.-B.; Hwang, M.-J.; Kim, B.-J.; Kim, H.-Y.; Park, Y.-J. Eﬀect of indium content on the
microstructure, mechanical properties and corrosion behavior of titanium alloys. Metals
Lee, B.-H.; Kim, Y.D.; Lee, K.H. XPS study of bioactive graded layer in Ti–In–Nb–Ta alloy prepared by alkali
and heat treatments. Biomaterials 2003,24, 2257–2266. [CrossRef]
Okazaki, Y.; Rao, S.; Ito, Y.; Tateishi, T. Corrosion resistance, mechanical properties, corrosion fatigue strength
and cytocompatibility of new Ti alloys without Al and V. Biomaterials 1998,19, 1197–1215. [CrossRef]
Niinomi, M.; Kuroda, D.; Fukunaga, K.-I.; Morinaga, M.; Kato, Y.; Yashiro, T.; Suzuki, A. Corrosion wear
fracture of new βtype biomedical titanium alloys. Mater. Sci. Eng. A 1999,263, 193–199. [CrossRef]
Wang, P.; Feng, Y.; Liu, F.; Wu, L.; Guan, S. Microstructure and mechanical properties of Ti–Zr–Cr biomedical
alloys. Mater. Sci. Eng. C 2015,51, 148–152. [CrossRef] [PubMed]
Correa, D.; Vicente, F.B.; Donato, T.; Arana-Chavez, V.; Buzalaf, M.; Grandini, C.R. The eﬀect of the solute
on the structure, selected mechanical properties, and biocompatibility of Ti–Zr system alloys for dental
applications. Mater. Sci. Eng. C 2014,34, 354–359. [CrossRef] [PubMed]
Xue, P.; Li, Y.; Li, K.; Zhang, D.; Zhou, C. Superelasticity, corrosion resistance and biocompatibility of the
Ti–19Zr–10Nb–1Fe alloy. Mater. Sci. Eng. C 2015,50, 179–186. [CrossRef]
Raducanu, D.; Vasilescu, E.; Cojocaru, V.D.; Cinca, I.; Drob, P.; Drob, S. Mechanical and corrosion resistance
of a new nanostructured Ti–Zr–Ta–Nb alloy. J. Mech. Behav. Biomed. Mater. 2011,4, 1421–1430. [CrossRef]
Lavos-Valereto, I.C.; König, B.; Rossa, C.J.; Marcantonio, E.J.; Zavaglia, A.C. A study of histological responses
from Ti-6Al-7Nb alloy dental implants with and without plasma-sprayed hydroxyapatite coating in dogs.
J. Mater. Sci. Mater. Med. 2001,12, 273–276. [CrossRef]
Srimaneepong, V.; Yoneyama, T.; Wakabayashi, N.; Kobayashi, E.; Hanawa, T.; Doi, H. Deformation properties
of Ti-6A1-7Nb alloy castings for removable partial denture frameworks. Dent. Mater. J.
Aridome, K.; Yamazaki, M.; Baba, K.; Ohyama, T. Bending properties of strengthened Ti-6Al-7Nb alloy major
connectors compared to Co-Cr alloy major connectors. J. Prosthet. Dent. 2005,93, 267–273. [CrossRef]
Yamazoe, J.; Nakagawa, M.; Matono, Y.; Takeuchi, A.; Ishikawa, K. The development of Ti alloys for dental
implant with high corrosion resistance and mechanical strength. Dent. Mater. J.
,26, 260–267. [CrossRef]
Kobayashi, E.; Wang, T.; Doi, H.; Yoneyama, T.; Hamanaka, H. Mechanical properties and corrosion resistance
of Ti–6Al–7Nb alloy dental castings. J. Mater. Sci. Mater. Electron. 1998,9, 567–574. [CrossRef]
Iijima, D. Wear properties of Ti and Ti–6Al–7Nb castings for dental prostheses. Biomaterials
Al-Mobarak, N.A.; Al-Swayih, A.A.; Al-Rashoud, F.A. Corrosion behavior of Ti-6Al-7Nb alloy in biological
solution for dentistry applications. Int. J. Electrochem. 2011,6, 2031–2042.
Shimojo, N.; Kondo, C.; Yamashita, K.; Hoshino, T.; Hayakawa, T. Cytotoxicity analysis of a novel titanium
: Adhesion, spreading, and proliferation of human gingival ﬁbroblasts. Biomed. Mater. Eng.
Pennekamp, P.H.; Gessmann, J.; Diedrich, O.; Burian, B.; Wimmer, M.A.; Frauchiger, V.M.; Kraft, C.N.
Short-Term microvascular response of striated muscle to Cp-Ti, Ti-6Al-4V, and Ti-6Al-7Nb. J. Orthop. Res.
2006,24, 531–540. [CrossRef]
Pennekamp, P.H.; Wimmer, M.A.; Eschbach, L.; Burian, B.; Koch, P.; Kraft, C.N. Microvasculatory reaction of
skeletal muscle to Ti–15Mo in comparison to Well-Established titanium alloys. J. Mater. Sci. Mater. Electron.
2007,18, 2053–2060. [CrossRef]
Osathanon, T.; Bespinyowong, K.; Arksornnukit, M.; Takahashi, H.; Pavasant, P. Ti-6Al-7Nb promotes cell
spreading and ﬁbronectin and osteopontin synthesis in Osteoblast-Like cells. J. Mater. Sci. Mater. Electron.
2006,17, 619–625. [CrossRef]
Castellano, A.; Gil, L.F.; Bonfante, E.A.; Tovar, N.; Neiva, R.; Janal, M.N.; Coelho, P.G. Early healing
evaluation of commercially pure titanium and Ti-6Al-4V presenting similar surface texture: An
study. Implant Dent. 2017,26, 338–344. [CrossRef]
Milosev, I.; Kosec, T.; Strehblow, H.-H. XPS and EIS study of the passive ﬁlm formed on orthopaedic
Ti–6Al–7Nb alloy in Hank’s physiological solution. Electrochim. Acta 2008,53, 3547–3558. [CrossRef]
Al-Nawas, B.; Hangen, U.; Duschner, H.; Krummenauer, F.; Wagner, W. Turned, machined versus
Double-Etched dental implants in vivo. Clin. Implant Dent. Relat. Res. 2007,9, 71–78. [CrossRef]
Pinholt, E.M. Bränemark and ITI dental implants in the human Bone-Grafted maxilla: A comparative study.
Clin. Oral Implants Res. 2003,14, 584–592. [CrossRef] [PubMed]
Boukari, A.; Francius, G.; Hemmerl
, J. AFM force spectroscopy of the ﬁbrinogen adsorption process onto
dental implants. J. Biomed. Mater. Res. Part A 2006,78, 466–472. [CrossRef]
Kirmanidou, Y.; Sidira, M.; Drosou, M.-E.; Bennani, V.; Bakapoulou, A.; Tsouknidas, A.; Michailidis, N.;
Michaolakis, K. New Ti-Alloys and surface modiﬁcations to improve the mechanical properties and biological
response to orthopaedic and dental implants: A review. BioMed Res. Int. 2016,2, 2908570.
Bagno, A.; Bello, C.D. Surface treatments and roughness properties of Ti-Based biomaterials. J. Mater. Sci.
Mater. Med. 2004,15, 935–949. [CrossRef]
Takadama, H.; Kim, H.M.; Kokubo, T.; Nakamura, T. An X-Ray photoelectron spectroscopy study of the
process of apatite formation on bioactive titanium metal. J. Biomed. Mater. Res.
,55, 185–193. [CrossRef]
Yamaguchi, S.; Takadama, H.; Matsushita, T.; Nakamura, T.; Kokubo, T. Cross-Sectional analysis of the
surface ceramic layer developed on Ti metal by NaOH-Heat treatment and soaking in SBF. J. Ceram. Soc. Jpn.
2009,117, 1126–1130. [CrossRef]
Pattanayak, D.K.; Yamaguchi, S.; Matsushita, T.; Nakamura, T.; Kokubo, T. Apatite-Forming ability of
titanium in terms of pH of the exposed solution. J. R. Soc. Interface 2012,9, 2145–2155. [CrossRef]
Kim, H.-M.; Himeno, T.; Kawashita, M.; Lee, J.-H.; Kokubo, T.; Nakamura, T. Surface potential change in
bioactive titanium metal during the process of apatite formation in simulated body ﬂuid. J. Biomed. Mater. Res.
2003,67, 1305–1309. [CrossRef]
Takadama, H.; Kim, H.M.; Kokubo, T.; Nakamura, T. TEM-EDX study of mechanism of bonelike apatite
formation on bioactive titanium metal in simulated body ﬂuid. J. Biomed. Mater. Res.
Kawanabe, K.; Ise, K.; Goto, K.; Akiyama, H.; Nakamura, T.; Kaneuji, A.; Sugimori, T.; Matsumoto, T. A new
cementless total hip arthroplasty with bioactive titanium Porous-Coating by alkaline and heat treatment:
Average 4.8-Year results. J. Biomed. Mater. Res. Part B Appl. Biomater. 2009,90, 476–481. [CrossRef]
So, K.; Kaneuji, A.; Matsumoto, T.; Matsuda, S.; Akiyama, H. Is the Bone-Bonding ability of a cementless
total hip prosthesis enhanced by alkaline and heat treatment? Clin. Orthop. Relat. Res.
Liu, X.; Chu, P.K.; Ding, C. Surface modiﬁcation of titanium, titanium alloys, and related materials for
biomedical applications. Mater. Sci. Eng. R Rep. 2004,47, 49–121. [CrossRef]
Leinenbach, C.; Eiﬂer, D. Inﬂuyence of oxidation on fatigue and fatigue-induced damage of commercially
pure titanium. Acta Biomater. 2009,5, 281002819. [CrossRef] [PubMed]
Yang, B.; Uchida, M.; Kim, H.-M.; Zhang, X.; Kokubo, T. Preparation of bioactive titanium metal via anodic
oxidation treatment. Biomaterials 2004,25, 1003–1010. [CrossRef]
Cui, X.; Kim, H.-M.; Kawashita, M.; Wang, L.; Xiong, T.; Kokubo, T.; Nakamura, T. Preparation of bioactive
titania ﬁlms on titanium metal via anodic oxidation. Dent. Mater. 2009,25, 80–86. [CrossRef]
Kuromoto, N.K.; Sim
o, R.A.; Soares, G.A. Titanium oxide ﬁlms produced on commercially pure titanium by
anodic oxidation with diﬀerent voltages. Mater. Charact. 2007,58, 114–121. [CrossRef]
Sul, Y.-T.; Johansson, C.B.; Jeong, Y.; Albrektsson, T. The electrochemical oxide growth behaviour on titanium
in acid and alkaline electrolytes. Med. Eng. Phys. 2001,23, 329–346. [CrossRef]
Chen, Z.X.; Takao, Y.; Wang, W.X.; Matsubara, T.; Ren, L.M. Surface characteristics and
of titanium anodized in a phosphoric acid solution at diﬀerent voltages. Biomed. Mater.
Zhang, B.G.X.; Myers, D.E.; Wallace, G.G.; Brandt, M.; Choong, P.F.M. Bioactive coatings for orthopaedic
Implants–Recent trends in development of implant coatings. Int. J. Mol. Sci. 2014,15, 11878–11921. [CrossRef]
Wheeler, S.L. Eight-Year clinical retrospective study of titanium Plasma-Sprayed and Hydroxyapatite-Coated
cylinder implants. Int. J. Oral Maxillofac. Implant 1996,11, 340–350. [CrossRef]
De Groot, K.; Geesink, R.; Klein, C.P.; Serekian, P. Plasma sprayed coatings of hydroxyapatite. J. Biomed.
Mater. Res. 1987,21, 1375–1381. [CrossRef]
Szmukler-Moncler, S.; Piattelli, A.; Favero, G.A.; Dubruille, J.-H. Considerations preliminary to the application
of early and immediate loading protocols in dental implantology. Clin. Oral Implant Res.
Gapski, R.; Wang, H.-L.; Mascarenhas, P.; Lang, N.P. Critical review of immediate implant loading. Clin. Oral
Implant Res. 2003,14, 515–527. [CrossRef] [PubMed]
135. Zablotsky, M.H. Hydroxyapatite Coatings in Implant Dentistry. Implant Dent. 1992,1, 253–257. [CrossRef]
Jung, J.-H.; Kim, S.-Y.; Yi, Y.-J.; Lee, B.-K.; Kim, Y.-K. Hydroxyapatite-Coated implant: Clinical prognosis
assessment via a retrospective Follow-Up study for the average of 3 years. J. Adv. Prosthodont.
85–92. [CrossRef] [PubMed]
Sugiyama, T.; Miake, Y.; Yajima, Y.; Yamamoto, K.; Sakurai, K. Surface observation of thin Hydroxyapatite-Coated
implants at 80 months after insertion. J. Oral Implant 2011,37, 273–278. [CrossRef] [PubMed]
Ong, J.L.; Chan, D.C.N. Hydroxyapatite and their use as coatings in dental implants: A review. Crit. Rev.
Biomed. Eng. 2000,28, 667–707. [CrossRef]
Yazdani, J.; Ahmadian, E.; Shariﬁ, S.; Shahi, S.; Dizaj, S.M. A short view on nanohydroxyapatite as coating of
dental implants. Biomed. Pharmacother. 2018,105, 553–557. [CrossRef]
Kim, S.K.; Lee, J.B.; Koak, J.Y.; Heo, S.-J.; Lee, K.R.; Cho, L.R.; Lee, S.S. An abutment screw loosening study of
a Diamond Like Carbon-coated CP titanium implant. J. Oral Rehabil. 2005,32, 346–350. [CrossRef]
Love, C.A.; Cook, R.B.; Harvey, T.J.; Dearnley, P.A.; Wood, R.J.K. Diamond-Like carbon coatings for potential
application in biological Implants—A review. Tribol. Int. 2013,63, 141–150. [CrossRef]
Manhabosco, T.M.; Martens, L.A.M.; Tamborin, S.M.; Ilha, M.; Vieira, M.Q.; Guma, F.C.R.; Müller, I.L.
Cell response and corrosion behaviour of electrodeposited Diamond-Like carbon ﬁlms on nanostructured
titanium. Corr. Sci. 2013,66, 169–176. [CrossRef]
Butter, R.; Allen, M.; Chandra, L.; Lettington, A.; Rushton, N.
studies of DLC coatings with silicon
intermediate layer. Diam. Relat. Mater. 1995,4, 857–861. [CrossRef]
Kim, H.-G.; Ahn, S.-H.; Kim, J.-G.; Park, S.J.; Lee, K.-R. Corrosion performance of Diamond-Like carbon
(DLC)-Coated Ti alloy in the simulated body ﬂuid environment. Diam. Relat. Mater.
Huacho, P.M.M.; Nogueira, M.N.M.; Basso, F.G.; Junior, M.J.; Francisconi, R.S.; Spolidorio, D.M.P. Analyses of
bioﬁlm on implant abutment surfaces coating with Diamond-Like carbon and biocompatibility. Braz. Dent. J.
2017,28, 317–323. [CrossRef] [PubMed]
2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).