Acta Biomaterialia 20 (2015) 176187

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Acta Biomaterialia
journal homepage: www.elsevier.com/locate/actabiomat

Development of TiNbZr alloys with high elastic admissible strain

for temporary orthopedic devices
Sertan Ozan a,b, Jixing Lin c,d, Yuncang Li e, Rasim Ipek b, Cuie Wen a,e,
a

Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia
Department of Mechanical Engineering, Ege University, 35100 Bornova, Izmir, Turkey
c
Advanced Material Research and Development Center, Zhejiang Industry & Trade Vocational College, Wenzhou, Zhejiang 325003, China
d
Department of Materials Science and Engineering, Jilin University, Changchun, Jilin 130025, China
e
School of Aerospace, Mechanical and Manufacturing Engineering, RMIT University, Melbourne, Victoria 3083, Australia
b

a r t i c l e

i n f o

Article history:
Received 13 September 2014
Received in revised form 19 March 2015
Accepted 20 March 2015
Available online 25 March 2015
Keywords:
Elastic admissible strain
Cytocompatibility
TNZ (TiNbZr) alloys
Mechanical properties
Youngs modulus

a b s t r a c t
A new series of beta TiNbZr (TNZ) alloys with considerable plastic deformation ability during
compression test, high elastic admissible strain, and excellent cytocompatibility have been developed
for removable bone tissue implant applications. TNZ alloys with nominal compositions of Ti34Nb
25Zr, Ti30Nb32Zr, Ti28Nb35.4Zr and Ti24.8Nb40.7Zr (wt.% hereafter) were fabricated using the
cold-crucible levitation technique, and the effects of alloying element content on their microstructures,
mechanical properties (tensile strength, yield strength, compressive yield strength, Youngs modulus,
elastic energy, toughness, and micro-hardness), and cytocompatibilities were investigated and compared.
Microstructural examinations revealed that the TNZ alloys consisted of b phase. The alloy samples displayed excellent ductility with no cracking, or fracturing during compression tests. Their tensile strength,
Youngs modulus, elongation at rupture, and elastic admissible strain were measured in the ranges of
704839 MPa, 6265 GPa, 9.914.8% and 1.081.31%, respectively. The tensile strength, Youngs modulus
and elongation at rupture of the Ti34Nb25Zr alloy were measured as 839 31.8 MPa, 62 3.6 GPa, and
14.8 1.6%, respectively; this alloy exhibited the elastic admissible strain of approximately 1.31%.
Cytocompatibility tests indicated that the cell viability ratios (CVR) of the alloys are greater than those
of the control group; thus the TNZ alloys possess excellent cytocompatibility.
2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

1. Introduction
According to a report by the United Nations in 2013 [1], the
population of the age group 60 years and older is increasing
rapidly, and in the more developed regions of the world, the ratio
of elderly people is expected to increase by 45% as of 2050.
Orthopedic biomaterials are implanted into human bodies in order
to heal bone tissue diseases developed due to aging, various congenital defects in bone tissue, injuries to bone tissue and joints
from trafc and sports accidents [2,3].
With the increasing utilization of orthopedic implant materials,
if biologically and mechanically compatible materials are not used
for implants, it is inevitable that the number of revision surgeries
will increase [4]. Genotoxic, cytotoxic, carcinogenic, mutagenic,
allergenic, neurological effects are taken into account while
Corresponding author at: School of Aerospace, Mechanical and Manufacturing
Engineering, RMIT University, Melbourne, Victoria 3083, Australia. Tel.: +61 3 9925
7290.
E-mail address: cuie.wen@rmit.edu.au (C. Wen).
http://dx.doi.org/10.1016/j.actbio.2015.03.023
1742-7061/ 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

evaluating the biological compatibility of an implant material [5].

The formation of stress shielding may occur in cases where an
implant material with a higher Youngs modulus than that of bone
tissue is used [6]. Resorption in bone tissue can occur when it
carries lower amounts of biological load due to a rigid implant
material carrying most of the loads [7]. In such cases, the implant
material may loosen [6]. The fact that titanium (Ti) alloys have a
lower Youngs modulus in comparison with 316L stainless steel
and CoCr alloys is an important factor in their increasing use as
implant materials [3].
Since Youngs modulus of the (a + b) Ti6Al4V alloy (at
110 GPa) [8] is about 4 times greater than that of cortical bone tissue (max. 27 GPa) [9], b Ti alloys with a relatively lower Youngs
modulus in comparison with a + b Ti alloys have been developed
for orthopedic implant applications [1016]. As it is well known,
among the Ti alloys, Ti6Al4V is still the most used one for orthopedic applications, even though it contains vanadium, which is
dened as toxic [17], as well as having aluminum, for which
neurological side-effects [18], and genotoxic effects [19] have been

S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

reported. Another important consideration is that the cold-forming

capabilities of b Ti alloys (e.g. Ti15Mo5Zr3Al) are much better
in comparison with a + b Ti alloys (e.g. Ti6Al4V) [20]. The superior cold-forming ability of b Ti alloys decreases the manufacturing
cost, thus creating an advantage for them in becoming commercial
products [4].
The role of CaP formations on implants surface is to accelerate
the assimilation of implant material and bone-tissue [21]. For
instance, on the surface of bio-inert Zirconia, calcium phosphate
formation enabling a chemical bond with the surrounding bonetissue does not occur, it only ensures morphological xation while
staying in the body [22]. CaP formations enable a tight bond
between the implant and surrounding bone-tissue [23]. On the
other hand, it is crucial to prevent the formation of brous tissue
between the bone-tissue and implants [24]. A direct contact without brosis tissue between implant material and bone is dened
as osseointegration. [24]. Implants may be isolated due to brous
tissue formed between the bone tissue and implant [25]. It is
beyond doubt that brous tissue formation between the implant
and surrounding tissue is not desired, it is a prerequisite for both
temporary and permanent implant materials. Unlike osseointegration, chemical bonding between implant and bone tissue is related
to calcium phosphate forming ability of implants [26]. The fast
formation of xation between the implant material and bone is provided by calcium phosphate precipitates on the surface of the
implant material, which thereby increases bone conduction [27].
Methods such as alkaline treatment [28], micro-arc oxidation [29]
and solgel [30] are used in order to enhance the adherence of
the implant material to the bone tissue or, in other words, to
increase chemical bonding ability by providing calcium phosphate
formation on the surface. Permanent implants (e.g. articial joints
and dental implants) should have an assimilation ability with bone
tissue when assessed on the basis of clinic needs [31]. It is expected
that such an implant should offer excellent bioactivity [32]. It is
well known that articial joints take on the natural joint function
by replacing the severely damaged joint. It is crucial to introduce
articial joints having the ability of assimilation with bone tissue
which ensures patients to carry out daily activities properly for
the rest of their lives [33]. When viewed under this aspect, the bone
conductivity of permanent implant materials should be high [31].
However, the reverse is required in removable implant applications [34]; that is, calcium phosphate precipitates are undesirable
on the surface of removable implants so as to minimize the bone
conductance of the implant material, and to prevent assimilation
between the bone tissue and the implant material [27]. Contrary
to permanent implants, the bonding between implant and bone
should be weak enough to prevent refracture of the bone during
removal surgery [35]. Trauma implants, e.g. bone nails, lose their
function after a healing period and they are removed after fracture
union [36]. Unlike articial joints, trauma implants (e.g. bone nails)
do not lead to any restriction of movement function when removed
from the body at an assigned time after healing period of the bone
tissue, i.e., it is not necessary to remain in the body permanently as
articial joints. Because of the tendency of calcium phosphate precipitation on the surface of some Ti alloys, assimilation occurs
between the bone tissue and the implant material which makes
them unadaptable as a choice of temporary implants [31]. It is crucial to avoid assimilation of these devices with bone tissue for an
easy removal surgery [37]. In cases where there is no assimilation
between bone and implant material, the occurrence of new bone
fractures during surgery to remove the implant material is minimized, and so the removal surgery is easier [34]. Implant removal
becomes necessary with patient demands and complaints [38].
Especially in the cases of implants used for athletes engaged in
contact sports [39] and for children [40], the implants may be
removed after a healing period [34]. This necessitates the design

177

of materials with a low Youngs modulus and high mechanical

strength, as well as low bone conductance for removable implant
applications [31,34,41]. Problems that arise during implant
removal surgery due to the assimilation of the bone and the
implant material can be prevented by inhibition of calcium phosphate precipitations on the surfaces of the implant materials [34].
It is possible to prevent bone atrophy during the time that the
implant stays in the body by using implant materials with a low
Youngs modulus [42]. By minimizing or eliminating the stress
shielding effect with the use of implant materials that have a low
Youngs modulus, problems relating to long recovery times of
patients following removal operations [39] can be resolved.
The objective of this study was to develop Ti alloys with low
rigidity, high mechanical strength, and reasonable elongation at
rupture for removable bone tissue implant applications. To this
end, studies showing that zirconium (Zr) prevents calcium phosphate formation on the surface of a material [27,43,44] and studies
describing the mechanical properties and phase stability changes
of TiNbZr alloys containing high amounts of Zr [45,46] were
taken into account, and TNZ alloys with high Zr element (between
25 wt.% and 40.7 wt.%) were manufactured. Niobium (Nb), another
of the alloy elements used in this study, is a b isomorphous alloy
element [47]. Whereas the effect of Zr on binary Ti alloys is evaluated as either neutral or weak b stabilization, Zr functions as an
effective b stabilizer in multi-element Ti alloys that contain Nb
or Ta [48]. In this study, the effects of Zr and Nb content on the
microstructures, mechanical properties, and cytocompatibility of
TNZ alloys with different electronic parameters were investigated
and compared.
2. Materials and methods
2.1. Alloy design
Using a trial-and-error method for the design of Ti alloys results
in time-consuming and uneconomical manufacturing processes
[49]. The approach developed by Morinaga et al. [50], known as
the d-electron alloy design method, exploits the relationship
between the phase stability and elastic properties of Ti alloys by
using the electronic parameters of average bond order (Bo ) and average metal d-orbital energy level (M d ) [48]. In the literature, there are
reports of many Ti alloys that have been designed using the d-electron alloy design method [11,5153]. It was reported by Abdel et al.
[48] that Youngs modulus decreases along the b/b + x phase
boundary with an increase in Bo and M d values, as seen in the
Bo  M d diagram (Fig. 1) (adapted and redrawn from Ref. [48],
Copyright (2006), with permission from Elsevier). b/b + x phase
boundary presented with a dotted curve in Fig. 1, means that, the
phase stability of titanium alloys depends on the amount of other
alloying elements (e.g. Hf, Zr), as explained in Ref. [45].
Bo is the measure of the covalent bond strength between Ti and
the alloying element, whereas the Md of the alloying transitionmetal is a value that relates the metallic radius of the elements
and their electronegativities [48]; these two parameters are values
that have been theoretically determined using the orbital method
in body-centered cubic titanium using the DV-Xa molecular orbital
method [48,50]. The average Bo and M d values are calculated using
the formula given by [54]:

Bo RX i Bo i

Md RX i M d i

where Xi is the atomic ratio of the given element, (Bo)i is the bond
order value of the given element [54], and (Md)i is the metal

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 1. Location of TNZ alloys on Bo  M d map and electronic parameters of TNZ

alloys (adapted and redrawn from Ref. [48], Copyright (2006), with permission from
Elsevier).

d-orbital energy level of the alloying transition-metal value of the

given element [54].
In this study, we combined the d-electron alloy design method
[50] with the molybdenum equivalence (Moeq) [55] and electron to
atom ratio ((e/a)ratio) [20] approaches in the design of the TNZ
alloys. The Moeq values were designed to be larger than 6 and
the (e/a)ratio of the TNZ alloys were in the range of 4.184.25. The
electronic parameters of the alloys including the Bo  M d values,
Moeq, and (e/a)ratio are summarized in Fig. 1 (adapted and redrawn
from Ref. [48], Copyright (2006), with permission from Elsevier).
The locations of the designed TNZ alloys are shown on the
Bo  M d graph, above and as close as possible to the b/b + x phase
boundary.
2.2. Material preparation
Since Ti is very active chemically at high temperatures, difculties may arise in obtaining a chemically homogeneous structure in
the production of Ti alloys in traditional arc or induction melting
furnaces, so the cold-crucible levitation melting method is used
for the production of Ti alloys via casting [51]. This method ensures
that the alloy is melted without any contact between the melt and
the melting crucible, and is also not affected by the melting point
difference between Ti and the alloying element [51]. The nominal
compositions of the TNZ alloys were Ti34Nb25Zr, Ti30Nb
32Zr, Ti28Nb35.4Zr and Ti24.8Nb40.7Zr; these alloys are
hereafter denoted TNZ-1, TNZ-2, TNZ-3, and TNZ-4, respectively.
As seen in Fig. 1 (adapted and redrawn from Ref. [48], Copyright
(2006), with permission from Elsevier), with an increase in the
concentration of Zr or a decrease in the concentrations of Nb and
Ti, the position of the alloy moves from TNZ-1 to TNZ-4 along
the b/b + x boundary. Simultaneously, the Bo  M d values increase,
while the Moeq value and the (e/a)ratio decrease. In the diagram, the
positions of the alloys are situated just above the boundary with as
close proximity as possible. Ingots of the alloys were re-melted 5
times in order to guarantee chemical homogeneity. Commercially
pure titanium (CP-Ti) Grade-2, furnished as cold worked, was used
as a control group for tensile test, as well.
2.3. Microstructural characterization
Disk-shaped samples with a diameter of 8 mm and thickness of
2 mm were cut from the ingots for phase analysis, microstructure

examination, and micro-hardness measurements using electrical

discharge machining (EDM). The samples used for microstructure
examination, phase analysis, and micro-hardness measurements
were consecutively ground with SiC grinding papers of up to
4000 grit. Following the grinding process, the samples were
polished using a colloidal silica and H2O2 mixture suspension,
and afterward the samples were cleaned for 5 min in an ultrasonic
bath using ethanol. Phase analyses of the samples were carried out
using a Bruker D8 Advance X-ray diffractometer (XRD) with a Cu
Ka radiation source at room temperature. Microhardness measurements were made on the polished surfaces of the samples in accordance with procedure listed in ASTM standard E384-94 [56] by
using microhardness tester (Buehler Micromet 2100). Nine different measurements were made, and the minimum and maximum
microhardness values were not taken into account when calculating the average micro-hardness values. The samples for
microstructure characterization were etched with Kroll solution.
The microstructure of TNZ alloys was examined by optical microscopy (Leica-MEF4M).
2.4. Mechanical property testing
Tensile samples with a gauge section of 8 mm  2 mm  1 mm
were cut using EDM. Both surfaces of the samples were ground
with SiC grinding papers of up to 2400 grit. Tensile tests were
carried out at 0.5 mm/min cross-head speed at room temperature
using an Instron 5567 testing system with advanced video extensometer. The gauge length of 8 mm was marked prior to the test
so that the video extensometer could detect it. Using the stress
strain curves obtained from the tensile tests, tensile strength, yield
strength, Youngs modulus, elastic energy, toughness and elongation at rupture of the TNZ alloys were measured.
The slope of the linear part of the stressstrain curves was determined as Youngs modulus, and the 0.2% offset yield method was
used to determine the yield strength of the TNZ alloys. Tensile tests
were repeated on 5 samples for each alloy, and the average values
obtained from the 5 measurements were used in the calculation
of the mechanical properties. The fracture surfaces of the tensile
samples were examined using eld-emission scanning electron
microscopy (SEM, ZEISS SUPRA 40 VP). Cylindrical samples 5 mm
in diameter and 8 mm in length were machined using EDM for compression tests. The tests were carried out at a cross-head speed of
0.5 mm/min, using an MTS testing system at room temperature in
accordance with procedure listed in ASTM standard E9-09 [57].
The compressive yield strength of the TNZ alloys was calculated
from the averages of 3 samples for each alloy. As it is seen in
Fig. 5 (indicated by blue arrow), the compressive stressstrain
graph of TNZ alloys display pre-deformation phenomenon [58]
which makes it impossible to use the 0.2% offset approach for
calculating the compressive yield strength of the alloys.
Consequently, two lines method [58] was used to be able to calculate the compressive yield strength of the alloys.
2.5. MTS assay
Disk samples 8 mm in diameter and 2 mm in thickness for cell
culture were cut from the ingots using EDM. All samples for the
cytocompatibility assessment were sterilized in a mufed furnace
at 180 C for 3 h. The cytocompatibility of all alloys was evaluated
using a direct cell method according to the International Standard
ISO10993-5 [59]. The disk shaped TNZ and CP-Ti specimens were
put into the wells of the cell culture plate. At a density of 5  103
cells per well (Barwon Biomedical Research, Geelong Hospital,
Victoria, Australia) were seeded onto the surface of the samples.
In order to determine the in vitro proliferation of cells, MTS
assay was used [60,61]. The cell morphology was observed by

S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

means of SEM after cell culturing. Prior to SEM observation of

SaOS2 cells attached to the surface of samples, a series of processes
were carried out. Samples, on which cells were seeded, were xed
in glutaraldehyde (3.9%) at room temperature for 1 h. Following
this process, dehydration of cells was performed by washing consecutively in ethanol solutions with a concentration of 60%, 70%,
80%, 90%, and 100%. Chemical drying of samples was performed
by using hexamethyldisilazane. Finally, by coating the samples
with gold, the samples were made ready for SEM observation. In
this study, all cell culture experiments were conducted in triplicate
and results were stated as means standard deviations.
2.6. Statistical analysis
The mechanical property values (tensile and yield strength,
Youngs modulus, elongation at rupture, elastic energy, toughness,
compressive yield strength, micro-hardness) and cell adhesion
density values were analyzed by using one-way ANOVA
(q < 0.05) followed by Tukey HSD post hoc test. q < 0.05 was taken
into consideration statistically signicant.
3. Results and discussion
3.1. Microstructure of the TNZ alloys
It was determined following microstructural examinations that
the TNZ alloys display primary grain boundaries together with secondary grain structure, as shown in Fig. 2. In Fig. 2(c), dendritic
structure was clearly observable.
The XRD patterns of the TNZ alloys are given in Fig. 3. As shown,
only b diffraction peaks were detected in each TNZ specimen. The
diffraction peaks of b Ti shifted toward lower 2h degree values with
increases in the amount of Zr or decreases in the amounts of Nb
and Ti in the alloys. Similar results were reported by Ning et al.
[62]; however, in that study [62], the Nb level was kept constant
while increasing the Zr and decreasing the Ti, and it was suggested
that, as a result of the increase in Zr, the atomic radius of which is
larger in comparison with Ti, a greater number of Zr atoms

179

replaced Ti atoms, resulting in a shift of the peaks toward lower

2h degree values [62].
3.2. Micro-hardness of the TNZ alloys
Fig. 4 presents the microhardness of the alloys in comparison
with that of other Ti alloys as published in the literature, respectively. As seen in Fig. 4, it is worth noting that the average microhardness levels of TNZ-1 (241.3 HV), TNZ-2 (244.4 HV), TNZ-3
(244.0 HV) and TNZ-4 (235.6 HV) are higher than those of CP-Ti
(134.0 HV) [63], Ti29Nb13Ta4.6Zr (solution treated condition
180 HV) [64] and Ti13Nb13Zr (solution treated condition
235 HV) [65], and lower than that of Ti6Al4V (as-cast 294
HV) [66]. The micro-hardness value of the TNZ-1,2,3 alloys was signicantly (q < 0.05) higher than that of the TNZ-4 alloy. When
ranked the average micro-hardness value of TNZ alloys among
themselves, the alloys are ranked TNZ-2 > TNZ-3 > TNZ-1 > TNZ-4.
3.3. Compressive properties of the TNZ alloys
The compressive stressstrain graphs of the TNZ alloys are
shown in Fig. 5. It can be seen that under compression, the alloys
exhibited considerable plastic deformation ability. As seen in
Fig. 5, the room temperature compression stressstrain curve of
the TNZ alloys is consisted of elastic stage (I), a plastic yield plateau
stage (II), a parabola stage (III) [67], consecutively. TNZ-2 displayed
the highest compressive yield strength among all the TNZ alloys,
and TNZ-3 displayed a compressive yield strength very close to
that of TNZ-2. Representative images of the alloy samples taken
before and after compression are inserted in Fig. 5, showing that
neither cracking nor fracturing was observed. Compression tests
were stopped after reaching a strain value of 65%.
The average compressive yield strength of the TNZ alloys is
given in Fig. 6. There are no signicant (q > 0.05) differences
among the compressive yield strength of the alloys. However,
when a ranking in terms of average compressive yield strength is
made, the alloys are ranked TNZ-2 > TNZ-3 > TNZ-1 > TNZ-4. The
small differences among the compressive yield strengths of the

Fig. 2. Optical micrographs of as-cast TNZ alloys: (a) TNZ-1; (b) TNZ-2; (c) TNZ-3; (d) TNZ-4.

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 3. XRD patterns of as-cast TNZ alloys.

Fig. 4. Microhardness of TNZ alloys in comparison with those of other Ti alloys published in the literature.

alloys may have been caused by different second-phase particles

[68], grain size, or solid-solution strengthening effects [69].
Similarly, it can be observed that the microhardness levels of the
alloys present the same ranking order (Fig. 4).
It is worth noting that the compressive yield strength of the TNZ
alloys is about 4 times greater than the compressive yield strength
of bone tissue (Human Haversian: 180 MPa) [70]. However, in

recent years, metal foam materials have been manufactured that

compromise on the mechanical strength of the implant material
in order to ensure that the Youngs modulus value of the material
is similar to that of bone tissue [61,71]. Even though the design of
foam material takes bone ingrowth into consideration [72], the use
of such materials, especially for orthopedic implants carrying high
loads, is still uncommon due to the fact that metal foams possess

S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

181

Fig. 5. Compressive stressstrain curve of as-cast TNZ alloys.

Fig. 6. Compressive yield strength of as-cast TNZ alloys.

lower mechanical strength, i.e. fatigue strength, tensile strength

and compression strength, in comparison with their solid counterparts [73]. The fact remains that, metal foams also possess lower
corrosion resistance [74].

3.4. Tensile properties of the TNZ alloys

Fig. 7 shows the stressstrain graphs of the TNZ alloys obtained
via tensile tests. The tensile properties (tensile strength, yield
strength, and elongation at rupture) of the alloys are given in
Fig. 8. TNZ-1 exhibited the highest average tensile strength and
yield strength, and largest elongation. The ranking of the average
tensile strength, yield strength, and elongation of the alloys from
the highest to lowest is TNZ-1 > TNZ-2 > TNZ-3 > TNZ-4. In particular, the elongation at rupture of the alloys was in the range of 9.9
14.8%. When the TNZ alloys were evaluated statistically among

themselves; it was determined that the tensile and yield strength,

elongation at rupture, toughness, elastic energy of TNZ-1 were signicantly (q < 0.05) higher than TNZ-3 and TNZ-4 alloy. The fact
remains that, TNZ-2 had signicantly (q < 0.05) higher tensile
and yield strength, elongation at rupture, toughness and elastic
energy than that of the TNZ-4, as well. However, there were no signicant differences (q > 0.05) in terms of Youngs modulus among
TNZ alloys. The tensile strength, yield strength, Youngs modulus
and elongation at rupture of the CP-Ti, used as a control in this
study, were measured as 758 14.1 MPa, 607 10.3 MPa,
109 1.1 GPa, and 26 0.2%, respectively. By statistically comparing Youngs modulus of CP-Ti and TNZ alloys, it was determined
that CP-Ti had signicantly (q < 0.05) higher Youngs modulus in
comparison with TNZ alloys.
It is noticeable that the elongation values of these as-cast TNZ
alloys are comparable to or slightly higher than those of the
thermomechanically processed biomedical Ti alloys currently in
use, such as Ti12Mo6Zr2Fe [75], Ti6Al7Nb [76], Ti15Mo
[77], Ti13Nb13Zr [78] and as-cast Ti6Al4V [79] with elongations of 12%, 10%, 12%, 15% and 8%, respectively. It should be noted
that as-cast Ti alloys generally present relatively lower elongation
values compared to those of their thermomechanically processed
counterparts [8]. However, the as-cast TNZ alloys studied in this
research exhibited fairly large elongation values that are comparable to those of the annealed Ti alloys noted above.
In the case of the elastic deformation of material, the ability to
release absorbed energy on unloading is known as resilience, and
this property is measured by the resilience modulus or elastic
energy [80]. In calculating the elastic energy of the TNZ alloys,
the yield strength was taken as the elastic limit [80]. Toughness
is a measure indicating the ability of a material to absorb energy
during tensile deformation till fracture [80]. The toughness values
obtained by calculating the area under the tensile curve along with
the elastic energy values denoting the absorbed energy when the
alloys deformed elastically, and Youngs modulus values of
the alloys are given in Fig. 9. The elastic energy and toughness of
the alloys were calculated using a Matlab-R2012b. The ranking

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 7. Tensile stressstrain curves of as-cast TNZ alloys.

Fig. 8. Tensile mechanical properties (tensile strength, yield strength and elongation at rupture) of TNZ alloys.

of the toughness and elastic energy of the alloys from the highest
to lowest is TNZ-1 > TNZ-2 > TNZ-3 > TNZ-4. As seen in Fig. 9, the
average Youngs modulus of the alloys was in the range of
6265 GPa.
Ti alloys that are used as implant material are required to possess high mechanical strength and a low Youngs modulus, so that
they can safeguard the host bone tissue without causing stress

shielding, which could lead to bone resorption and cause implant

loosening [81]. The mechanically compatible performance of an
orthopedic implant material can be evaluated by the elastic admissible strain [82], the ratio of yield strength to Youngs modulus of
the material given by [4]:

d r=E

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 9. Tensile mechanical properties (Youngs modulus, elastic energy and toughness) of TNZ alloys.

Table 1
Comparison of mechanical properties of TNZ alloys with those of some commercial titanium alloys.
Ti alloys

Yield strength
(MPa)

Tensile strength
(MPa)

Youngs
modulus (GPa)

Elongation (%)

Elastic admissible
Strain (%)

Alloy type

References

Pure Ti (Grade 4)
Ti16Nb10Zr (annealed)
Ti15Mo (annealed)
Ti-6-4 ELI (mill annealed)
Tiadyne 1610 (aged)
Ti35.3Nb5.1Ta7.1Zr (annealed)
Ti29Nb13Ta4.6Zr (annealed)
CP-Ti (cold worked)
Ti34Nb25Zr (TNZ-1)
Ti32Zr30Nb (TNZ-2)
Ti35.4Zr28Nb (TNZ-3)
Ti40.7Zr24.8Nb (TNZ-4)

485
485
544
875
736
547

607 10.3
810 48.0
782 18.8
729 26.3
682 52.9

550
520
874
965
851
597
549
758 14.1
839 31.8
794 10.1
755 28.3
704 49.5

104.1
70
78
110
81
55
60
109 1.1
62 3.6
65 4.2
64 4.5
63 4.2

15
22
21
1015
I0
19
41.6
26 0.2
14.8 1.6
13 1.8
11.3 1.5
9.9 1.1

0.47
0.69
0.70
0.80
0.91
0.99

0.56
1.31
1.20
1.14
1.08

[8]
[83]
[84]
[84]
[84]
[8]
[81]
[This
[This
[This
[This
[This

where d is the elastic admissible strain, r is the yield strength and E

is Youngs modulus of the material.
The mechanical properties of the TNZ alloys investigated in this
study, and of Ti16Nb10Zr [83] and some of the commercial Ti
alloys [8,81,84] published in the literature are listed in Table 1.
As can be seen, the elastic admissible strain values of the TNZ
alloys are in the range of 1.081.31%, and the highest elastic admissible strain value for commercial Ti alloys stated in Table 1 is 0.99%
for annealed Ti35.3Nb5.1Ta7.1Zr [8]. It can be concluded that
the TNZ alloys would offer promising performance in practical
applications in terms of mechanical compatibility. The Youngs
modulus values of TNZ-1, TNZ-2, TNZ-3, and TNZ-4 are 62.0 3.6,
65.0 4.2, 64.0 4.5 and 63.0 4.2 GPa, respectively. Youngs
modulus values of the TNZ alloys are lower than those of pure
CP-Ti (104 GPa) [8] and mill-annealed Ti6Al4V (110 GPa) [84],
and close to those of Ti35.3Nb5.1Ta7.1Zr (55 GPa) [8] and
Ti29Nb13Ta4.6Zr (60 GPa) [81].
The fracture surfaces of the TNZ alloys after tensile tests are
shown in Fig. 10. It can be seen that the alloys exhibited a ductile

b + a
b
a+b
b
b
b

a
b
b
b
b

study]
study]
study]
study]
study]

fracture surface with numerous dimples, exemplied by the white

arrows in Fig. 10(ad). It is noticeable that the number of dimples
for TNZ-1 is particularly large and the dimples observed on the
fracture surface are deeper, in comparison with TNZ-2, TNZ-3,
and TNZ-4. In addition, cleavages (indicated by the black arrows
in Fig. 10) were observed accompanying the dimples on the fracture surfaces of the alloys. In particular, cleavage was the predominant fracture mechanism in TNZ-4. It is well known that the
fracture surfaces of ductile materials are rougher, whereas those
of brittle materials are smooth. Intergranular fracturing, which is
one of the indicators of brittle fracturing, was not observed on
the fracture surfaces of the alloys.

3.5. Cytocompatibility of the TNZ alloys

The healthy adhesion of osteoblast cells to the implant surface,
and their growth and proliferation, are important indicators of the
cytocompatibility of the implant materials [61]. To this end, the

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 10. Fracture surfaces of as-cast TNZ alloys (a) TNZ-1; (b) TNZ-2; (c) TNZ-3; (d) TNZ-4.

Fig. 11. Morphology of SaOS2 cells attached on the surface of TNZ-2 alloy after cell
culture for 24 h.

in vitro cytocompatibility of the TNZ alloys was assessed using

SaOS2 cells.
Following the cell culture of the TNZ alloys for 24 h, the surfaces
of alloys were examined in terms of the morphology of osteoblast
cells using SEM. The adherence of osteoblast cells to the surfaces of
the samples is shown in Fig. 11. It can be seen that the osteoblast
cells started to proliferate following 24 h of cell culture. The osteoblast cells on the alloy surfaces display a polygonal morphology,
and a large number of lopodia have formed, providing anchoring
of the osteoblast cells on the materials surfaces (Fig. 11). The formation of lopodia on the surfaces after cell culture is an indication that the initial cell adhesion and the growth of the cells
were healthy and strong [85]. Thus it can be concluded that the
TNZ alloys are favorable for cell growth and proliferation.
SEM images of the SaOS2 osteoblast cells on the surfaces of the
TNZ alloys after cell culture for 7 days are given in Fig. 12. It can be
seen that the SaOS2 cells display a healthy growth on the surfaces
of the alloys. Numerous osteoblast cells rmly adhered to and
spread over the alloy surfaces. There was no difference in terms

of the morphology of the osteoblast cells on the four different alloy

surfaces (Fig. 12). Unhealthy cells are distinguished from healthy
cells on the basis of their reduced cell morphology caused by
shrinkage of the cells [86]. When this morphological property
specic to unhealthy cells was considered, it was observed that
very healthy cells proliferated on the surfaces of the alloys.
Fig. 13 shows a comparison of cell adhesion density for the TNZ
alloys and CP-Ti after 7 days of cell culture. After assessment of the
images of the osteoblast cells on the alloy surfaces, along with the
cell adhesion densities given in Fig. 13, it can be concluded that
osteoblast cells adhered well to the surfaces, and spread and grew
in a healthy way. As can be seen from Fig. 13, the average cell adhesion density of the TNZ alloys is greater than that of CP-Ti. Ranking
of the TNZ alloys and CP-Ti in terms of average cell adhesion density is TNZ-4 > TNZ-3 > TNZ-2 > TNZ-1 > CP-Ti. No signicant differences (q > 0.05) were conrmed in cell adhesion densities
between CP-Ti and TNZ-1, TNZ-2, TNZ-3 alloys. However, the cell
adhesion density of TNZ-4 was signicantly (q < 0.05) higher than
CP-Ti. According to the obtained results, an increase in Zr in the
TNZ alloys and decreases in Nb and Ti result in an increase in cell
adhesion density. The highest cell adhesion density among the
alloys is that of TNZ-4, which also has the highest Zr (40.7%) and
the lowest Nb (24.8%) and Ti (35.5%). The three elements of Ti,
Nb, and Zr are all biocompatible elements, as previously reported
[8789].
Cells were seeded in the wells having only the medium within,
as well. As a negative control, they were incubated for the same
days. The cell viability ratios (CVR) of CP-Ti and the TNZ alloys
were calculated by dividing the live SaOS2 cell number inside the
experimental wells by the live SaOS2 cell number inside the control; the control group has a CVR of 1 and is accepted as being
cytocompatible as a reference in determining the cell viability
ratios of samples [85]. Fig. 14 presents the CVR values that enabled
assessment of the in vitro cytotoxicity of the TNZ alloys and CP-Ti.
The CVR values of the TNZ alloys were all greater than those of the
control group; hence it can be deduced that the alloys possess
exceptional cytocompatibility. In addition, the cell proliferation
ratios were similar in the experimental wells of the CP-Ti and
TNZ disks, so their cell viability ratio values are also very close
(Fig. 14).

S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

185

Fig. 12. SEM images of SaOS2 cells attached on to surfaces of TNZ alloys after cell culture for 7 days: (a) TNZ-1; (b) TNZ-2; (c) TNZ-3; (d) TNZ-4.

Fig. 13. SaOS2 cell adhesion density of as-cast TNZ alloys and CP-Ti after cell culture for 7 days.

4. Conclusions
The microstructures, mechanical properties and cytocompatibility of the as-cast TiNbZr alloys have been examined. The conclusions are as follows:
1. Microstructural examinations revealed that the TNZ alloys display primary grain boundaries together with secondary grain
structure.
2. The average compressive yield strength and microhardness
values of the TNZ alloys exhibited the same ranking: TNZ2 > TNZ-3 > TNZ-1 > TNZ-4. The alloys exhibited considerable

ductility under compression and no fracturing or cracking was

observed on the samples after the compression tests. The compressive yield strength of the alloys ranged from 713 to 751 MPa.
3. Tensile test results showed that the TNZ alloys have elongation
at rupture values in the range of 9.914.8%, which is highly
desirable for biomedical applications. The tensile strength of
the TNZ alloys was in the range of 704839 MPa and Youngs
modulus was in the range of 6265 GPa.
4. The TNZ alloys exhibited elastic admissible strain values in the
range of 1.081.31%. Ti34Nb25Zr exhibited an elastic admissible strain of 1.31%, the highest value compared to TNZ alloys
studied in this project.

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S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

Fig. 14. Cell viability ratio of as-cast TNZ alloys and CP-Ti.

5. The tensile strength, yield strength, elongation, elastic energy,

and toughness of the TNZ alloys all decreased when the Zr content increased and the amounts of Ti and Nb decreased. In other
words, the tensile mechanical properties decreased with a
decrease in the (e/a)ratio and Moeq values.
6. The TNZ alloys exhibited excellent cytocompatibility on SaOS2
cells.
7. The TNZ alloys designed in this study are suitable candidates for
removable orthopedic implant applications due to their high Zr
content, high elastic admissible strain value, superior plastic
deformation ability during compression test, and excellent
cytocompatibility.

Acknowledgments
SO would like to acknowledge the Council of Higher Education
(CoHE) of Turkey for PhD research scholarship. CW acknowledges
the nancial support from the Australian Research Council (ARC)
through the ARC Discovery Project DP110101974.
Appendix A. Figures with essential color discrimination
Certain gures in this article, particularly Figs. 5 and 79 are difcult to interpret in black and white. The full color images can be
found in the on-line version, at http://dx.doi.org/10.1016/j.actbio.
2015.03.023.
References
[1] Division UNDoEaSAP. World population prospects: the 2012 revision, Key
ndings and advance tables. New York; 2013. p. 1-50.
[2] Navarro M, Michiardi A, Castano O, Planell JA. Biomaterials in orthopaedics. J R
Soc Interface/R Soc 2008;5:113758.
[3] Geetha M, Singh AK, Asokamani R, Gogia AK. Ti based biomaterials, the
ultimate choice for orthopaedic implants a review. Prog Mater Sci
2009;54:397425.
[4] Abdel-Hady Gepreel M, Niinomi M. Biocompatibility of Ti-alloys for long-term
implantation. J Mech Behav Biomed Mater 2013;20:40715.

[5] Biesiekierski A, Wang J, Gepreel MA, Wen C. A new look at biomedical Ti-based
shape memory alloys. Acta Biomater 2012;8:16619.
[6] Huiskes R, Weinans H, Vanrietbergen B. The relationship between stress
shielding and bone-resorption around total hip stems and the effects of exible
materials. Clin Orthop Relat Res 1992:12434.
[7] Black J. Biological performance of materials, fundamentals of biocompatibility.
4th ed. Boca Raton, FL: CRC Taylor & Francis; 2006.
[8] Niinomi M. Mechanical properties of biomedical titanium alloys. Mater Sci Eng
1998;243:2316.
[9] Rho JY, Tsui TY, Pharr GM. Elastic properties of human cortical and trabecular
lamellar bone measured by nanoindentation. Biomaterials 1997;18:132530.
[10] Hao YL, Li SJ, Sun SY, Zheng CY, Yang R. Elastic deformation behaviour of Ti
24Nb4Zr7.9Sn for biomedical applications. Acta Biomater 2007;3:27786.
[11] Kuroda D, Niinomi M, Morinaga M, Kato Y, Yashiro T. Design and mechanical
properties of new beta type titanium alloys for implant materials. Mater Sci
Eng 1998;243:2449.
[12] Li Q, Niinomi M, Nakai M, Cui Z, Zhu S, Yang X. Effect of Zr on super-elasticity
and mechanical properties of Ti24 at% Nb(0, 2, 4) at% Zr alloy subjected to
aging treatment. Mater Sci Eng, A 2012;536:197206.
[13] Matsumoto H, Watanabe S, Hanada S. Beta TiNbSn alloys with low Youngs
modulus and high strength. Mater Trans 2005;46:10708.
[14] Miyazaki S, Kim HY, Hosoda H. Development and characterization of Ni-free
Ti-base shape memory and superelastic alloys. Mater Sci Eng, A 2006;438
440:1824.
[15] Ozaki T, Matsumoto H, Watanabe S, Hanada S. Beta Ti alloys with low Youngs
modulus. Mater Trans 2004;45:27769.
[16] Yang G, Zhang T. Phase transformation and mechanical properties of the
Ti50Zr30Nb10Ta10 alloy with low modulus and biocompatible. J Alloy Compd
2005;392:2914.
[17] Okazaki Y. A new Ti-15Zr-4Nb-4Ta alloy for medical applications. Curr Opin
Solid State Mater Sci 2001;5:4553.
[18] Flaten TP. Aluminium as a risk factor in Alzheimers disease, with emphasis on
drinking water. Brain Res Bull 2001;55:18796.
[19] Lima PD, Vasconcellos MC, Montenegro RC, Bahia MO, Costa ET, Antunes LM,
et al. Genotoxic effects of aluminum, iron and manganese in human cells and
experimental systems: a review of the literature. Hum Exp Toxicol
2011;30:143544.
[20] Boyer R, Welsch G, Collings EW, editors. Materials properties handbook:
titanium alloys. Materials Park, OH, USA: ASM International; 1994.
[21] Anselme K. Biomaterials and interface with bone. Osteoporosis Int
2011;22:203742.
[22] Liu XY, Huang AP, Ding CX, Chu PK. Bioactivity and cytocompatibility of
zirconia (ZrO2) lms fabricated by cathodic arc deposition. Biomaterials
2006;27:390411.
[23] Yuan H, de Groot K. Calcium phosphate biomaterials: an overview. In: Reis RL,
Weiner S, editors. Learning from nature how to design new implantable
biomaterialsis: from biomineralization fundamentals to biomimetic materials
and processing routes. Netherlands: Springer; 2005. p. 3757.

S. Ozan et al. / Acta Biomaterialia 20 (2015) 176187

[24] Carlsson L, Rstlund T, Albrektsson B, Albrektsson T, Brnemark P-I.
Osseointegration of titanium implants. Acta Orthopaedica 1986;57:2859.
[25] Liu XY, Chu PK, Ding CX. Surface modication of titanium, titanium alloys, and
related materials for biomedical applications. Mater Sci Eng R Rep
2004;47:49121.
[26] Skripitz R, Aspenberg P. Tensile bond between bone and titanium a
reappraisal of osseointegration. Acta Orthop Scand 1998;69:3159.
[27] Kobayashi E, Ando M, Tsutsumi Y, Doi H, Yoneyama T, Kobayashi M, et al.
Inhibition effect of zirconium coating on calcium phosphate precipitation of
titanium to avoid assimilation with bone. Mater Trans 2007;48:3016.
[28] Kim HM, Miyaji F, Kokubo T, Nakamura T. Effect of heat treatment on apatiteforming ability of Ti metal induced by alkali treatment. J Mater Sci Mater Med
1997;8:3417.
[29] Tsutsumi Y, Niinomi M, Nakai M, Tsutsumi H, Doi H, Nomura N, et al. Microarc oxidation treatment to improve the hard-tissue compatibility of Ti29Nb
13Ta4.6Zr alloy. Appl Surf Sci 2012;262:348.
[30] Li YC, Xiong JY, Wong CS, Hodgson PD, Wen CE. Bioactivating the surfaces of
titanium by SolGel process. Mater Sci Forum 2009;614:6771.
[31] Hanawa T. Research and development of metals for medical devices based on
clinical needs. Sci Technol Adv Mater 2012;13:064102.
[32] Simka W, Krzakala A, Maselbas M, Dercz G, Szade J, Winiarski A, et al.
Formation of bioactive coatings on Ti13Nb13Zr alloy for hard tissue
implants. RSC Adv 2013;3:11195204.
[33] Fujibayashi S, Nakamura T. Current status of bioactive coatings in Japan.
Fifteen years of clinical experience with hydroxyapatite coatings in joint
arthroplasty. Paris: Springer; 2004. p. 11524.
[34] Zhao X, Niinomi M, Nakai M, Ishimoto T, Nakano T. Development of high Zrcontaining Ti-based alloys with low Youngs modulus for use in removable
implants. Mater Sci Eng, C 2011;31:143644.
[35] Niinomi M. Low modulus titanium alloys for inhibiting bone atrophy.
Biomater Sci Eng 2011. Prof. Rosario Pignatello (Ed.), ISBN: 978-953-307609-6, InTech, 2011. Available from: <http://www.intechopen.com/books/
biomaterials-science-and-engineering/low-modulus-titanium-alloysforinhibiting-bone-atrophy>.
[36] Sidky A, Buckley RE. Hardware removal after tibial fracture has healed. Can J
Surg 2008;51:2638.
[37] Hanawa T, Tsutsumi Y. Calcium phosphate formation on titanium and zirconium
and its application to medical devices. Bioceramics Dev Appl 2010;1:14.
[38] Vos DI, Verhofstad MHJ. Indications for implant removal after fracture healing:
a review of the literature. Eur J Trauma Emerg Surg 2013;39:32737.
[39] Evans NA, Evans RON. Playing with metal: fracture implants and contact sport.
Br J Sports Med 1997;31:31921.
[40] Schmittenbecher PP. Implant removal in children. Eur J Trauma Emerg Surg
2013;39:34552.
[41] Zhao X, Niinomi M, Nakai M, Miyamoto G, Furuhara T. Microstructures and
mechanical properties of metastable Ti30Zr(Cr, Mo) alloys with changeable
Youngs modulus for spinal xation applications. Acta Biomater
2011;7:32306.
[42] Niinomi M, Nakai M. Titanium-based biomaterials for preventing stress
shielding between implant devices and bone. Int J Biomater 2011;2011:
836587.
[43] Hanawa T, Okuno O, Hamanaka H. Compositional change in surface of TiZr
alloys in articial bioliquid. J Jpn Inst Met 1992;56:116873.
[44] Hanawa T, Hiromoto S, Asami K, Okuno O, Asaoka K. Surface oxide lms on
titanium alloys regenerated in Hanks solution. Mater Trans 2002;43:30004.
[45] Abdel-Hady M, Fuwa H, Hinoshita K, Kimura H, Shinzato Y, Morinaga M. Phase
stability change with Zr content in beta-type TiNb alloys. Scripta Mater
2007;57:10003.
[46] You L, Song X. First principles; study of low Youngs modulus TiNbZr alloy
system. Mater Lett 2012;80:1657.
[47] Henry S, Dragolich K, DiMatteo N. Fatigue data book: light structural
alloys. Materials Park, OH: ASM International; 1995.
[48] Abdel-Hady M, Hinoshita K, Morinaga M. General approach to phase stability
and elastic properties of b-type Ti-alloys using electronic parameters. Scripta
Mater 2006;55:47780.
[49] Laheurte P, Prima F, Eberhardt A, Gloriant T, Wary M, Patoor E. Mechanical
properties of low modulus beta titanium alloys designed from the electronic
approach. J Mech Behav Biomed Mater 2010;3:56573.
[50] Morinaga M, Yukawa N, Maya T, Sone K, Adachi H. Theoretical design
of titanium alloys. In: Sixth world conference on titanium, vol. 1. France; 1988.
p. 16016.
[51] Matsugi K, Endo T, Choi Y-B, Sasaki G. Alloy design of Ti alloys using ubiquitous
alloying elements and characteristics of their levitation-melted alloys. Mater
Trans 2010;51:7408.
[52] Zhang DC, Lin JG, Jiang WJ, Ma M, Peng ZG. Shape memory and superelastic
behavior of Ti7.5Nb4Mo1Sn alloy. Mater Des 2011;32:46147.
[53] Saito T, Furuta T, Hwang JH, Kuramoto S, Nishino K, Suzuki N, et al.
Multifunctional alloys obtained via a dislocation-free plastic deformation
mechanism. Science 2003;300:4647.
[54] Morinaga M, Yukawa H. Alloy design with the aid of molecular orbital method.
Bull Mater Sci 1997;20:80515.
[55] Bania PJ. Beta-titanium alloys and their role in the titanium industry. JOM J
Miner Met Mater Soc 1994;46:169.
[56] ASTM E384-11e1. Standard test method for Knoop and Vickers hardness of
materials. West Conshohocken, PA: ASTM International; 2011. <www.astm.org>.

187

[57] ASTM E9-09. Standard test methods of compression testing of metallic

materials at room temperature. West Conshohocken, PA: ASTM
International; 2009. <www.astm.org>.
[58] Alshehri O, Yavuz M, Tsui T. Manifestation of external size reduction effects on
the yield point of nanocrystalline rhodium using nanopillars approach. Acta
Mater 2013;61:4050.
[59] Biological evaluation of medical devices. Part 5: Test for in vitro
cytotoxicity. Arlington, VA: International Organization for Standardization,
ANSI/AAMI; 1999.
[60] Li Y, Xiong J, Hodgson PD, Wen Ce. Effects of structural property and surface
modication of Ti6Ta4Sn scaffolds on the response of SaOS2 cells for bone
tissue engineering. J Alloy Compd 2010;494:3239.
[61] Li Y, Xiong J, Wong CS, Hodgson PD, Wen Ce. Ti6Ta4Sn alloy and subsequent
scaffolding for bone tissue engineering. Tissue Eng Part A 2009;15:31519.
[62] Ning C, Ding D, Dai K, Zhai W, Chen L. The effect of Zr content on the
microstructure, mechanical properties and cell attachment of Ti35NbxZr
alloys. Biomed Mater 2010;5:045006.
[63] Bertrand E, Gloriant T, Gordin DM, Vasilescu E, Drob P, Vasilescu C, et al.
Synthesis and characterisation of a new superelastic Ti25Ta25Nb
biomedical alloy. J Mech Behav Biomed Mater 2010;3:55964.
[64] Ushida K, Tsuge K, Akahori T, Hattori T, Niinomi M, Ishikura K, et al.
Mechanical strength and biocompatibility of meta-stable beta type Ti5Fe
3Nb3Zr for biomedical applications. J Jpn Inst Met 2012;76:397401.
[65] Geetha M, Singh AK, Muraleedharan K, Gogia AK, Asokamani R. Effect of
thermomechanical processing on microstructure of a Ti13Nb13Zr alloy. J
Alloy Compd 2001;329:26471.
[66] Ho WF, Ju CP, Lin JHC. Structure and properties of cast binary TiMo alloys.
Biomaterials 1999;20:211522.
[67] Yang Y, Wu SQ, Li GP, Li YL, Lu YF, Yang K, et al. Evolution of deformation
mechanisms of Ti22.4Nb0.73Ta2Zr1.34O alloy during straining. Acta
Mater 2010;58:277887.
[68] Li C, Zhan Y, Jiang W. Beta-type TiMoSi ternary alloys designed for
biomedical applications. Mater Des 2012;34:47982.
[69] Nie L, Zhan Y, Liu H, Tang C. Novel b-type ZrMoTi alloys for biological hard
tissue replacements. Mater Des 2014;53:812.
[70] Currey JD. Bones: structure and mechanics. Princeton: Princeton University
Press; 2002.
[71] Wang X, Li Y, Xiong J, Hodgson PD, Wen Ce. Porous TiNbZr alloy scaffolds for
biomedical applications. Acta Biomater 2009;5:361624.
[72] Hutmacher DW. Scaffolds in tissue engineering bone and cartilage.
Biomaterials 2000;21:252943.
[73] Ryan G, Pandit A, Apatsidis DP. Fabrication methods of porous metals for use in
orthopaedic applications. Biomaterials 2006;27:265170.
[74] Dabrowski B, Swieszkowski W, Godlinski D, Kurzydlowski KJ. Highly porous
titanium scaffolds for orthopaedic applications. J Biomed Mater Res B Appl
Biomater 2010;95:5361.
[75] ASTM F1813-13. Standard specication for wrought titanium-12 molybdenum-6
zirconium-2 iron alloy for surgical implant (UNS R58120). West Conshohocken,
PA: ASTM International; 2013. <www.astm.org>.
[76] ASTM F1295-05. Standard specication for wrought titanium-6 aluminum-7
niobium alloy for surgical implant applications (UNS R56700). West
Conshohocken, PA: ASTM International; 2005. <www.astm.org>.
[77] ASTM F2066-08. Standard specication for wrought titanium-15 molybdenum
alloy for surgical implant applications (UNS R58150). West Conshohocken,
PA: ASTM International; 2008. <www.astm.org>.
[78] ASTM F1713-08. Standard specication for wrought titanium-13niobium13zirconium alloy for surgical implant applications (UNS R58130). West
Conshohocken, PA: ASTM International; 2013. <www.astm.org>.
[79] ASTM F1108-04. Standard specication for titanium-6aluminum-4vanadium
alloy castings for surgical implants (UNS R56406). West Conshohocken,
PA: ASTM International; 2004. <www.astm.org>.
[80] Callister WD. Materials science and engineering: an introduction. 7th ed. New
York: John Wiley and Sons; 2007.
[81] Akahori T, Niinomi M, Koyanagi Y, Kasuga T, Toda H, Fukui H, et al. Mechanical
properties of biocompatible beta-type titanium alloy coated with calcium
phosphate invert glass-ceramic layer. Mater Trans 2005;46:15649.
[82] Song Y, Xu DS, Yang R, Li D, Wu WT, Guo ZX. Theoretical study of the effects of
alloying elements on the strength and modulus of beta-type bio-titanium
alloys. Mater Sci Eng 1999;260:26974.
[83] Zhang J, Sun F, Hao Y, Gozdecki N, Lebrun E, Vermaut P, et al. Inuence of
equiatomic Zr/Nb substitution on superelastic behavior of TiNbZr alloy.
Mater Sci Eng, A 2013;563:7885.
[84] Wang K. The use of titanium for medical applications in the USA. Mater Sci Eng
1996;213:1347.
[85] Li Y, Wen C, Mushahary D, Sravanthi R, Harishankar N, Pande G, et al. MgZr
Sr alloys as biodegradable implant materials. Acta Biomater 2012;8:317788.
[86] Li Y, Wong C, Xiong J, Hodgson P, Wen C. Cytotoxicity of titanium and titanium
alloying elements. J Dent Res 2010;89:4937.
[87] Eisenbarth E, Velten D, Muller M, Thull R, Breme J. Biocompatibility of betastabilizing elements of titanium alloys. Biomaterials 2004;25:570513.
[88] Geurtsen W. Biocompatibility of dental casting alloys. Crit Rev Oral Biol Med
2002;13:7184.
[89] Yamamoto A, Honma R, Sumita M. Cytotoxicity evaluation of 43 metal salts
using murine broblasts and osteoblastic cells. J Biomed Mater Res
1998;39:33140.