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Opinion Piece

Biocompatibility of Ti-alloys for long-term implantation

Mohamed Abdel-Hady Gepreela,n, Mitsuo Niinomib

aDepartment of Materials Science and Engineering, Egypt-Japan University of Science and Technology (E-JUST), Alexandria, Borgelarab

21934, EgyptbInstitute for Materials Research, Tohoku University, Sendai 980-8577, Japan

a r t i c l e i n f o

Article history:

Received 17 July 2012

Received in revised form

6 November 2012

Accepted 17 November 2012

Available online 6 December 2012

Keywords:

Implants

Compatibility

Long-term implantation

Ti-alloys

Low cost implants

nt matter & 2012 Elsevie.1016/j.jmbbm.2012.11.01

hor. Tel.: þ20 11 47375539geprell@yahoo.com (M. A

a b s t r a c t

The design of new low-cost Ti-alloys with high biocompatibility for implant applications,

using ubiquitous alloying elements in order to establish the strategic method for suppres-

sing utilization of rare metals, is a challenge. To meet the demands of longer human

life and implantation in younger patients, the development of novel metallic alloys

for biomedical applications is aiming at providing structural materials with excellent

chemical, mechanical and biological biocompatibility. It is, therefore, likely that the next

generation of structural materials for replacing hard human tissue would be of those

Ti-alloys that do not contain any of the cytotoxic elements, elements suspected of causing

neurological disorders or elements that have allergic effect. Among the other mechanical

properties, the low Young’s modulus alloys have been given a special attention recently, in

order to avoid the occurrence of stress shielding after implantation. Therefore, many

Ti-alloys were developed consisting of biocompatible elements such as Ti, Zr, Nb, Mo, and

Ta, and showed excellent mechanical properties including low Young’s modulus. However,

a recent attention was directed towards the development of low cost-alloys that have a

minimum amount of the high melting point and high cost rare-earth elements such as Ta,

Nb, Mo, and W. This comes with substituting these metals with the common low cost, low

melting point and biocompatible metals such as Fe, Mn, Sn, and Si, while keeping excellent

mechanical properties without deterioration. Therefore, the investigation of mechanical and

biological biocompatibility of those low-cost Ti-alloys is highly recommended now lead

towards commercial alloys with excellent biocompatibility for long-term implantation.

& 2012 Elsevier Ltd. All rights reserved.

1. Background

The continual growth of the world population and the

increase in traffic accidents especially for young people, more

pronounced in the developing countries (WHO, 2012), have

brought an ever-increasing need for materials specially suited

for bio-implant applications. Up till now, over 7 million

r Ltd. All rights reserved.4

; fax: þ20 304599520.bdel-Hady Gepreel).

Branemark System implants have been placed in human

bodies (Nabeel, 2012), over 1,000,000 spinal rod implantations

have been done between 1980–2000, and 250,000 total hip

replacements are performed annually in United States only

(Christian, 2004). Not only the replacement surgeries have

increased, but also the revision surgeries of hip and knee

implants. These revision surgeries which cause pain for the

j o u r n a l o f t h e m e c h a n i c a l b e h a v i o r o f b i o m e d i c a l m a t e r i a l s 2 0 ( 2 0 1 3 ) 4 0 7 – 4 1 5408

patient are very expensive, besides, their success rate is

rather small. The total number of hip revision surgeries is

expected to increase by 137% and that of knee revision

surgeries by 607% between the years 2005 and 2030 (Kurtz

et al., 2007). Nowadays, researchers are working hard to

develop materials for long life implantation in human body.

This is because the commercial biomaterials have exhibited

tendencies to fail after long-term use due to various reasons

such as low fatigue strength, high modulus compared to that

of bone, low wear and corrosion resistance and lack of

biocompatibility. The various causes for revision surgery

and the key solutions are schematically illustrated in Fig. 1.

Another acceptable reason for the increase in the number of

revision surgeries is the higher life expectancy. The implants

are now expected to serve for much longer period or until

lifetime without failure or revision surgery. The development

of appropriate material with high longevity and excellent

biocompatibility is highly essential.

Generally, the most common materials used in orthopedic

implants are metals and a type of plastic called polyethylene.

These two material types are combined in most joint implants,

that is, one component is made from metal, and one from

polyethylene. When properly designed and implanted, the two

components can rub together smoothly while minimizing

wear. Although some pure metals have excellent character-

istics for use as implants, most metallic implants are made

Fig. 1 – Various causes for failure of implants that leads to r

performance.

from alloys, namely, stainless steels, cobalt–chromium alloys,

and titanium alloys (Geetha et al., 2009).

Various metallic materials have been used for total hip

replacements as well as other joint replacement surgeries,

i.e., knees, shoulders, bone plates. Additional applications

include trauma and spinal fixation devices, cardiovascular

stents, and most recently replacement of spinal discs (Rack

and Qazi, 2006; Semlitisch, 1987).

Stainless steel shows moderate mechanical properties and

good corrosion resistance in human body fluid environment;

therefore, it is most often used in implants that are intended

to help in fractures repair, such as bone plates, bone screws,

pins, and rods. Cobalt–chromium alloys are also strong, hard,

biocompatible, and corrosion resistant; hence, they are used

in a variety of joint replacement implants, as well as some

fracture repair implants, that require a long service life.

In recent years, titanium and titanium alloys are extensively

used as bone replacement implants due to their excellent

mechanical properties, corrosion resistance and biocompat-

ibility as compared to the other metallic materials (Liu et al.,

2004; Tian et al., 2010).

Below is a systematic discussion on the main concepts

driving the progress in metallic implants research in the last

two decades ended with results of newly developed alloys.

This discussion will focus on the importance of both the

biological and mechanical biocompatibility for the long-life

evision surgery, footed with a proposed system for better

j o u r n a l o f t h e m e c h a n i c a l b e h a v i o r o f b i o m e d i c a l m a t e r i a l s 2 0 ( 2 0 1 3 ) 4 0 7 – 4 1 5 409

implants. In order to prevent failure after implantation, the

mechanical biocompatibility emphasizing the importance of

low Young’s modulus and how to achieve it, are also presented.

Finally, some economical considerations for the production of

new metallic implants will be discussed. This review will help

materials researchers to develop competitive materials for

implant applications, as well as its importance for surgeons to

choose the most proper materials for specific application.

2. Biological biocompatibility of implants

As explained above, the most common implants used long time

ago are made from stainless steel, titanium and Ti-alloys

(mainly due to their high corrosion resistance) and Co–Cr-based

alloys (mainly due to their high wear and corrosion resistance.)

In other words, these alloys are considered chemically stable

with respect to the internal chemistry of the human body

(i.e., good chemical biocompatibility). Even though the metals

used in implants are quite corrosion-resistant, there are still

some interchanges of metal ions into the tissues or tissue fluids

(Orden et al., 1982). The amount of metal ions released is related

to the corrosion resistance of the metal, the environmental

Table 1 – Selected orthopedic alloys developed and/or utilized(E¼elastic modulus, YS¼yield stress, UTS¼ultimate tensile s

Alloy designation (mass%) Microstructure E

Bone Viscoelastic composite 1nnStainless steel 316L Austenite 2

Annealed [1]

Hot forged [1]nnCoCrMo Austenite 2

Cast [1]

Wrought [1]nncp Ti (grade 4) a 1

Annealed [2]nnTi–6Al–4V aþb 1

Annealed [1]

Hot forged [1]nnTi–6Al–7Nb aþb 1

Annealed [3]nnTi–5Al–2.5Fe aþb 1

Cast [3]

Annealed [3]nnTi–13Nb–13Zr aþb 7

annealed[2]nnTi-11.5Mo–6Zr–4.5Sn (BIII) bAnnealed [3] 7nnTi–15Mo–5Zr–3Al b 8

Annealed [2]

Ti–15Mo–3Nb–0.3O b 8

Annealed [4]nnTi–35Nb–5Ta–7Zr (TNZT) b 5

Annealed [4]nnTi–35Nb–5Ta–7Zr–0.4O (TNZTO) bAnnealed [4] 6

Ti–29Nb–13Ta–4.5Zr b 6

(TNTZ) annealed[5]

[1] Ref. (Semlitsch and Willert, 1980) [2] Ref. (Li, 2000) [3] Ref. (Boyer et aa At 107 cycles.nn Commercially used in biomedical applications.

conditions (i.e., pH, chloride ion concentration, temperature,

etc.), mechanical factors (i.e., pre-existing cracks, surface abra-

sion, and film adhesion), electrochemical effects (i.e., applied

potential, galvanic effects, pitting, or crevices), and the dense

cell concentrations around implants (Oshida, 2006).

Reported in Table 1 are the common metals and alloys that

are used in implant applications, their microstructure and

their mechanical properties. As shown in this table, the

majority of implants contain; vanadium, aluminum, cobalt,

copper, chromium, molybdenum, nickel, titanium and var-

ious elements. It is well known that any metal surrounded by

biological systems will suffer corrosion to some extent

(Hallab et al., 2001). The biological biocompatibility of any

implant, which is defined by its toxicity, carcinogenicity, and

metal sensitivity from the release of metal ions, must be

quantified to decrease the patient’s risk and failure of

implants. Corrosion and the release of metal ions due to

the wear of the implant inside the human body are the source

of many adverse pathophysiological effects (Gotman, 1997).

That is why, the biological effect of elements, metals, and

alloys are being extensively studied.

For example, the cytotoxicity of typical surgical implant

alloys and pure metals have been studied by many

as biomedical implants and their mechanical propertiestrength).

(GPa) YS (MPa) UTS (MPa) Fatigue limit (MPa)a

0–30 90–140

00

170 480 145

140 585 295

00–230

450 565 400

860 1200 500

05

480 550 350

10

680 780 400

900 1000 600

05

800 900 500

10

820 900 425

780 860 725

9

900 1030 500

9 620 690 525

0

900 930 540

2

1020 1020 490

5

530 590 265

6 976 1010 450

5

400 420 325

l., 2007) [4] Ref. (Narayan, 2012) [5] Ref. (Niinomi and Nakai, 2011).

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researchers as reported in Biesiekierski et al. (2012); Davidson

and Kovacs (1989); Kuroda et al. (1998); Okazaki et al. (1996),

Steinemann (1980). Vanadium is classified in the sterile

abscess (toxic) group, and aluminium in the capsule (scar

tissue) group. Ti, Zr, Nb and Ta exhibit excellent biocompat-

ibility and are in the loose connective vascularized (vital)

group regarding tissue reaction. Kawahara reported that Ti,

Zr, Ta and Pd are low cytotoxic elements (Kawahara et al.,

1963). From the above information it is concluded that the

ideal biomaterial should possess good biological biocompat-

ibility by being free of toxic elements. Therefore, the stainless

steel, Co–Cr-based and Ti–6Al–4V alloys, the most common

implants alloys, are not the ideal alloys to be used for long

term implantation in human body from the biological point

of view, due to their high content of high cytotoxic elements

such as (V, Ni, Coy). Nickel is also known as allergenic

carcinogen element that exhibits one of the highest sensitiv-

ities in metallic allergen tests (Koster et al., 2000).

Therefore, the research on development of Ni-free

Co-based (Yamanaka et al., 2011) and Ti-based (Oak et al., 2009)

alloys are being done. In the same way, intensive efforts are

being done to substitute Ti–6Al–4V alloy with V-free titanium

alloys for biomedical applications. For this reason Ti–6Al–7Nb

and Ti–5Al–2.5Fe have been developed (Semlitsch et al., 1985;

Zwicker et al., 1980). However, it was reported that Al is an

element involved in severe neurological, e.g., Alzheimer’s

disease and metabolic-bone disease, e.g., osteomalacia

(Boyce et al., 1992). So, V- and Al-free Ti-alloys are being

developed too. One of the important V- and Al-free Ti-alloys

is Ti–13Nb–13Zr alloy (Steinemann et al., 1993) being free of

toxic elements and showing improved bone biocompatibility

and corrosion resistance compared to that of Co–Cr-based

and Ti–6Al–4V alloys (Davidson et al., 1994). Due to other

concerns such as mechanical biocompatibility, as will be

discussed below, many other b-type Ti alloys composed of

the high biocompatible elements (i.e., Ta, Nb, Zr, Mo, W, Sn, ..)

were developed such as Ti–29Nb–13Ta–4.6Zr (TNTZ) (Kuroda

et al., 1998), Ti–35Nb–5Ta–7Zr (TNZT), Ti–12Mo–6Zr–2Fe

(Steinemann, 1980), Ti–Mo and many others.

3. Mechanical biocompatibility of implants

The metallic implants, in many cases, should not only avoid

short-term rejection and infection, but should also provide

long-term biocompatibility and avoid long-term materials

limitations. Besides the biological biocompatibility discussed

above, the mechanical biocompatibility is vital for long term

implantation (He and Hagiwara, 2006). In this section, the

mechanical biocompatibility (i.e., high strength, long lifetime,

high-wear resistance and low Young’s modulus) is discussed.

3.1. Fatigue and wear resistance

The cyclic loading is applied to orthopedic implants during

body motion, resulting in alternating plastic deformation of

microscopically small zones of stress concentration produced

by notches or microstructural inhomogeneities. Therefore,

the long lifetime of implant, which is related to its fatigue

resistance, is a crucial property of implant materials. Shown

in Table 1 are the strength and fatigue strength of common

alloys used in implant manufacture. The strength and so

fatigue strength of alloys are related to the alloy composition

and prior thermo-mechanical processing history. Fatigue

strength is also highly affected by surface processing, finish-

ing and treatments. Hence, the alloys show a range of such

important mechanical properties and can be controlled with

proper processing and heat treatments. It is well known that

the higher the fatigue strength of an alloy is, the longer

lifetime for an implant made of it is in service. Generally,

Co–Cr alloys and (aþb)-type Ti-alloys show high fatigue

resistance when compared to other metallic biomaterials.

Recently, TNTZ (a b-type Ti-alloy) showed high fatigue

strength too with proper thermomechanical treatments

(Niinomi and Nakai, 2011). It is worthy to highlight here that

the notch sensitivity, which is changing with microstructure

control, is a very important aspect, since it can lead to poor

fatigue performance in some materials which have high

strength and fatigue strength (Li, 2000).

In addition, the other mechanical properties (such as

Young’s modulus and wear resistance) should be also con-

sidered, because they may limit the usage of the alloys in

manufacturing implants even if the strength and fatigue

strength are mechanically biocompatible.

Stainless steel and Co–Cr alloys show good wear resistance

and relatively high strength compared to that of bone, as

shown in Table 1. In addition, good fatigue resistance is

achievable, through microstructure control. However, these

materials still suffer from a large degree of biomechanical

incompatibility, due to their high elastic modulus (about

200 GPa), compared to that of the bone (max. 30 GPa).

3.2. Stiffness of implants

As mentioned above, when these alloys with low stiffness

mismatch with bone are used as a hip implant, e.g., a femoral

stem, the implant takes over a considerable part of body

loading, which shields the bone from the necessary stressing

required to maintain its strength, density, and healthy struc-

ture. Such an effect, usually termed ‘‘stress shielding’’,

eventually causes bone loss, implant loosening, and prema-

ture failure of the artificial hip (Mansour et al., 1995).

Therefore, these alloys are not recommended in general in

manufacturing implants that transfer loads to bone for long

term implantation (more than 10 years) (Oshida, 2006).

The stiffness of titanium and its alloys is substantially

lower than that of other conventional metallic implant

materials such as stainless steel or Co–Cr–Mo alloys, as

shown in Table 1. Therefore, compared to stainless steel

and Co–Cr alloys, Ti-based alloys are excellent biomaterials

for long-term implantation due to their relatively low Young’s

modulus, good fatigue resistance and excellent biological

passivity (Song et al., 1999a). However, the most common Ti

alloys used in bio-implantation are of a and aþb type alloys

that still show relatively high elastic modulus (about 120 GPa)

when compared with that of bone (max. 30 GPa), these

materials still suffer from a considerable degree of biome-

chanical incompatibility.

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One of the examples is the application of Ti–6Al–4V as a

femoral stems in total hip replacements. This alloy has a

relatively high elastic modulus (about 110 GPa) and stress

shielding is reported when it is used as femoral stem (Oshida,

2006). Moreover, the existing alloy can release toxic ions (e.g.,

V and Al) into the body, leading to undesirable long-term

effects (Cui and Guo, 2009; Kuroda et al., 1998; Lopez et al.,

2001; Oshida, 2006).

Therefore, the decrease of the Young’s modulus of implants

was an important target for the researchers in the last two

decades. It is well known that the Young’s modulus changes

according to the type of the phases existing in the alloy

(Matlakhova et al., 2005; Zhou et al., 2004a). For example, it

has been reported that the o-phase has the highest Young’s

modulus, and the martensite a0 0-phase has a lower modulus

than the martensite a0-phase, and the b-phase has the lowest

modulus among these phases in most Ti alloys (Matlakhova

et al., 2005; Zhou et al., 2004b). Thus, extensive investigations

have been carried out to develop b-type alloys with a low

Young’s modulus, superelasticity, shape memory effect and

satisfactory biocompatibility for the replacement of human

bone (Ikehata et al., 2004; Matlakhova et al., 2005; Niinomi,

2003; Saito et al., 2003).

The research of biomedical titanium alloy focused on

b-type titanium alloys which contain non-toxic elements

such as Nb, Ta, Zr, Mo and Sn in order to obtain lower elastic

modulus, higher corrosion resistance and improved tissue

response (Hallab et al., 2001; Oshida, 2006). Therefore,

b-titanium alloys can now replace the Ti–6Al–4V alloy which

is considered the most important biomedical titanium alloy.

Various b-type Ti-alloys have been developed and meet the

above mentioned needs of showing low Young’s modulus and

being free of toxic elements or elements that cause allergic

effect. Namely, Ti–15Mo–5Zr–3Al (Semlitsch et al., 1985),

Ti–12Mo–6Zr–2Fe (Okazaki et al., 1996), Ti–15Mo, Ti–29Nb–

13Ta–4.6Zr (Kuroda et al., 1998), Ti–35Nb–5Ta–7Zr and Ti–

13Zr–13Nb (Steinemann et al., 1993), have been developed

for medical implant applications. All these alloys show low

Young’s modulus as compared to that of Ti–6Al–4V alloy.

Moreover, the superelastic and shape memory behavior

observed in Ti–Ni alloy have made it widely applied to

biomedical uses. But Ni is a toxic element, as explained

above, that is why the development of Ni-free superelastic

and shape memory alloys was a recent target of many

researchers too. For example, Ti–Nb–X (X¼Zr, Ta, Mo, Au,

Pd, Pt, Al, Ga, Ge, Sn, Sc, O), Ti–Mo–Y (Y¼Ta, Nb, Zr, Au, Pd, Pt,

Al, Ga, Ag) and Ti–V–Z (Z¼Nb, Sn, Al) alloys were designed to

improve the superelastic and the shape memory property of

the biomedical Ti-alloy (Duerig et al., 1982; Hosoda et al.,

2003; Kim et al., 2004; 2005; Kuramoto et al., 2006; Song et al.,

1999a; 1999b; Zhou et al., 2004a; 2004b).

However, most of these compositions were formulated prin-

cipally by trial and error, which by no means represents the

optimum choices. There has been little theoretical investigation

to guide alloy development for high strength and low modulus

biomedical applications using, for example, the d-electrons

concept (Kuroda et al., 1998; Matsugi et al., 2010), and first

principles electronic calculations (Song et al., 1999a) and others.

In a recent study (Kuroda et al., 1998), some b�type

titanium alloys composed of non-toxic elements Nb, Ta, Zr,

Mo and Sn were designed based on molecular orbital calcula-

tions of electronic structures. Niimomi et.al. has developed

Ti–29Nb–13Ta–4.6Zr (TNTZ) alloy that shows Young’s modu-

lus as low as 60 GPa. However, TNTZ and other recently

developed alloys with relatively low Young’s modulus, such

as Ti–35Nb–5Ta–7Zr (TNZT), Ti–15Mo–2.8Nb–3Al and others,

show relatively low ultimate tensile strength and fatigue

strength, as shown in Table 1. It is important to stress again

here that the strength and fatigue strength of an alloy can be

improved through the proper post treatments. For example,

the strength and fatigue strength of TNTZ alloy raised

significantly from 420 and 325 MPa in the solution treatment

condition to 1100 and 775 MPa after thermomechanical treat-

ments, respectively (Niinomi and Nakai, 2011). However, this

is on the expense of an increase in the Young’s modulus from

65 to 85 GPa after the treatments.

Therefore, considerable efforts have been devoted by mate-

rials engineers and researchers to develop new b-titanium

with high strength and low modulus.

3.3. Ti-alloys with low Young’s modulus

The Young’s modulus changes with b�phase stability as was

discussed in details in previous studies (Abdel-Hady et al.,

2006, 2007, 2008, 2009). The least stable single b�phase alloys

show minimum values in Young’s modulus in the b�type

alloys (Abdel-Hady et al., 2006). Also, it was reported that the

Zr addition (Abdel-Hady et al., 2007; 2009) as well as small

addition of oxygen enhanced the elastic properties of the

Ti-alloys. Also, both Zr and O worked as b�stabilizers in the

b�type Ti-alloys (Abdel-Hady et al., 2006, 2009). With the aid

of Bo�Md diagram, the present author has developed new

high Zr-content alloys free of toxic elements. These alloys

showed high strength (more than 1200 MPa) and low Young’s

modulus (less than 50 GPa) under different treatments, as

shown in Fig. 2. Detailed discussion of the mechanical and

physical properties of these alloys is presented elsewhere

(Abdel-Hady and Morinaga, 2009a; 2009b)). Here, Bo is the

average bond order between atoms, and Md is the average d-

orbital energy level (eV) of the elements in the alloy. In the

same way, Ti–24Nb–4Zr–7.9Sn alloy was developed and

showed high strength (850 MPa) and low Young’s modulus

(42 GPa) (Hao et al., 2007). Many researchers are concerned

with increasing the strength and decreasing the Young’s

modulus of biocompatible b-type Ti-alloys through alloy

design, thermomechanical treatments and manufacturing

methods.

It is important to note that cold deformation of b-type

Ti-alloys contributes in controlling the Young’s modulus of

the alloy depending on the deformation technique and the

final microstructure, since deformation and/or recrystalliza-

tion textures are developed under some thermomechanical

schemes, as observed here in Fig. 2. Controlling the grain size

and introducing texture in the alloy through the proper

thermomechanical treatments have been reported by many

authors (Hosoda et al., 2006; Kim et al., 2006; Kuramoto et al.,

2006) and considered as very effective tool to reach the target

in developing more mechanical-biocompatible implants.

0

300

600

900

1200

UT

S (M

Pa)

ST CR

0

20

40

60

80

Z00 Z01 Z11Z00 Z01 Z11

You

ng's

mod

ulus

(GPa

)

Fig. 2 – Effect of phase stability and thermomechanical treatment on the Young’s modulus (a), and the ultimate tensile

strength (UTS) (b), of theTi67Zr20Nb10Ta3, Z00, Ti66Zr20Nb10Ta3O1, Z01, and Ti65Zr20Nb10Ta3Fe1O1, Z11, alloys after solution

treatment (ST) and after 90%CR (CR).

Fig. 3 – Elastic admissible strain plotted against Young’s

modulus of bone compared to the commercial biomedical

alloys (namely; stainless steel, SUS-316L, Co–Cr based alloy,

CoCrMo, Ti–6Al–4V, Ti–64ELI, commercial pure Ti, Cp–Ti,

Ti–35Nb–5Ta–7Zr–0.4O, TNZTO, and Ti–13Zr–13Nb) and the

recently developed alloys (namely; Ti–29Nb–13Ta–4.6Zr, TNTZ,

Ti–30Zr–8Mo, Ti-8Mo Ti65Zr20Nb10Ta3Fe1O1, Z11, and Ti–5Fe–

3Nb–3Zr, TFNZ), all in the annealing condition, are promising

for future long-term implant applications as they show elastic

admissible strain higher than the commercial alloys.

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A useful relation between strength and Young’s modulus

that guides materials selection for bio-implant applications is

presented as the elastic admissible strain of an alloy. The

elastic admissible strain, defined as the yield stress-to-

modulus ratio, is a quite important parameter considered in

orthopedic applications. The higher the elastic admissible

strain is, calculated from this relation, the more suitable the

materials for such applications are (Song et al., 1999a; 1999b).

It is important to mention here that the Young’s modulus of

alloys is measured at loads close to zero. However, some of

the recently b-type Ti-alloys show nonlinear elasticity (Saito

et al., 2003; Abdel-Hady et.al., 2008). Hence, these alloys

are showing higher elastic strain than calculated from

this relation and become more suitable for orthopedic

applications. Fig. 3 shows the elastic admissible strain of

the most common bio-implant alloys in addition to the most

promising b-type Ti-alloys developed recently for implant

applications. The recently designed alloys Z11 (ST and CR)

showed elastic admissible strain higher than other low

Young’s modulus Ti-alloys including the high Zr-content

alloys (i.e., Ti–30Zr–8Mo) (Niinomi and Nakai, 2011). Interest-

ing is Z11 alloy show nonlinear elasticity and the actual

elastic strain of this alloy is more than 2%. Z11 alloy seems

promising for future long-life implant applications since it

shows elastic admissible strain even higher than that of bone

itself.

Also the production technique and the implant structure

became recently tools to reduce the Young’s modulus of

metallic implants. Much research is being carried out to

produce metallic implants with cellular structure that show

very low Young’s modulus. For example, Ti–6Al–4V alloy with

cellular structure showed low Young’s modulus as low as

50 MPa (Cansizoglu et al., 2008; Li et al., 2006). The strength

and Young’s modulus of cellular structures are well

controlled through struts width, angles and relative density

of the structure (Cansizoglu et al., 2008; Li et al., 2006;

Schwerdtfeger et al., 2010).

4. Low cost implants

As discussed above, the future long term metallic implants

should be made of those alloys that show high mechanical

compatibility (i.e., high strength, high wear resistance and

low Young’s modulus) and are composed of non-toxic ele-

ments. The most promising alloys for implant applications

are b�type titanium alloys. That is why, many b�type

titanium alloys composed of non-toxic elements Nb, Ta, Zr,

Mo, Hf, Au, Pd, Pt, Ag, Ga, Ge, Sc, and Sn were developed in

the last two decades (Cui and Guo, 2009; Kuroda et al., 1998;

Lopez et al., 2001; Niinomi, 2003).

However, most of these developed b-titanium alloys con-

tain considerable amounts of the expensive, high melting

point, and high density metals (such as; Nb, Ta, Zr, and Mo).

These elements are also rare ones due to their low abun-

dances in the earth’s crust. In contrast, titanium is consid-

ered to be a ubiquitous element since it has the tenth highest

Clarke number of all the elements. This leads to high cost of

the raw materials and difficulty in the alloy preparation due

to the high melting points of the constituent elements that

leads to macro- and micro-segregations (Narita et al., 2012;

Zhou et al., 2006). Generally, the production cost and/or

difficulty of any alloy limit its range of applications and are

j o u r n a l o f t h e m e c h a n i c a l b e h a v i o r o f b i o m e d i c a l m a t e r i a l s 2 0 ( 2 0 1 3 ) 4 0 7 – 4 1 5 413

considered the main reasons behind the ease of commercia-

lization of any Ti-alloys. Many of the recently developed

alloys failed to compete with the commercial alloys due to

the difficulty in its production and their high content of

expensive rare earth metals (i.e., Nb, Ta, Zr, and Mo).

In addition, it is important for the strategy of developing

titanium alloys for high performance is using ubiquitous

elements of the alloying.

Consequently, there is a great need to develop new b�type

Ti alloys for biomedical applications, composed of non-toxic

and low cost common metals, such as Mn, Fe, Si and Sn

(Helsen and Bremr, 1998), that show high strength, high

corrosion resistance and low Young’s modulus. However,

the minimum Young’s modulus reported for the binary

Ti–M (M¼Mn and Fe) alloys is 95 GPa which, in some sense,

is still high compared to that of bone, while Ti–N (N¼Si and

Sn) binary alloys would intrinsically show high Young’s

modulus. This is because Si and Sn are a�stabilizing

elements and they cannot maintain b�phase as the predo-

minant phase in the alloy when added alone to the alloys.

Therefore, the co-addition of b-stabilizing elements with

these elements is essential to have b-type alloys.

The author reported in a previous work that, in b-type

Ti-alloys, the Young’s modulus is decreasing with increasing

the Bo value of the alloy in the Bo�Mddiagram (Abdel-Hady

et al., 2006; Kuroda et al., 1998). In Bo�Mddiagram, the

alloying vectors of Fe, Mn, Si and Sn are going to lower

Bo values (Abdel-Hady et al., 2007). Therefore, to design

b-titanium alloys with low Young’s modulus, it is still important

to co-add the elements with high Bo values (i.e., Mo, Nb, Ta,

Zr and Hf) (Abdel-Hady et al., 2006, 2007) even with small

quantities. Using the Bo�Mddiagram would be very useful in

achieving this aim. For example, Ti–Fe–Ta and Ti–Fe–Ta–Zr

alloys were developed for bio-implant applications with the

aid of Bo-Mddiagram (Kuroda et al., 2005). Also, with the aid

of Bo�Mddiagram, the present author is developing new low

cost Ti–Fe–Nb–Zr alloys (TFNZ) that show Young’s modulus of

75 GPa and UTS of 1169 MPa, detailed explanation will be

presented elsewhere. The TFNZ alloy shows elastic admissi-

ble strain higher than TNTZ, Cp Ti, Ti-64 ELI and SUS-316L,

and comparable to the alloys with high content of the

expensive rare earth metals. This means that the proposed

low cost and biocompatible Ti-alloys for long-time implanta-

tion can compete with the other commercial alloys and even

the recently developed b-type Ti-alloys from mechanical

biocompatibility point of view at least.

Another very important advantage of b-titanium alloys to

be commercialized is its high cold workability. This is

because the production cost of the implants is highly

concerned with the easiness of formation or manufacturing.

Due to many technical considerations (namely; surface finishing,

dimensional accuracy, sub-deformation treatments and heating

process) the cold forming ability is a cost effective process if

compared to the cost of hot forming of Ti-alloys.

5. Conclusion

Considering both the mechanical and biological biocompat-

ibility of implants, the production cost, and using ubiquitous

alloying elements in order to establish the strategic method

for suppressing utilization of rare metals, it seemed that the

future metallic implants for long-term usage would be those

b�type Ti alloys, composing mainly of low cost common

metals such as Mn, Sn or Fe, that show high strength, low

Young’s modulus and good cold workability.

Acknowledgments

Part of the experimental work presented in this paper

was done at the laboratory and under the supervision of

Prof. Masahiko Morinaga, Nagoya University, Japan. This

study was supported partially by a Grant-in-Aid for Scientific

Research from the Ministry of Education, Culture, Sports,

Science and Technology of Japan, the Japan Society for the

Promotion of Science, by the 21st centaury Global Center of

Excellence of Japan (G-COE), and by Science and Technology

Research Fund (STDF), Egypt.

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