Titanium

Overview

Recent Titanium R&D for Biomedical

Applications in Japan
Mitsuo Niinomi

Author’s Note: All compositions are given in mass percent
unless otherwise noted.
Titanium alloys composed of nontoxic el-
ements are being studied in Japan for use in
biomedical applications. The alloys being
studied are primarily α + β- and β-type
titanium alloys. Areas of research include
surface treatments to improve biocompat-
ibility and methods of preventing fretting
fatigue, a primary cause of failure in bio-
materials.
INTRODUCTION
The development of titanium alloys
for biomedical and dental applications
is currently an area of active research in
Japan. Both α + β- and β-type biomedical
titanium alloys composed of nontoxic
alloying elements are under investiga-
tion. Among the areas being studied are
surface treatments and fretting fatigue,
1.8
1.6
Coefficient of Fibroblastic Outgrowth
one of the main causes for failure of
biomaterials.
A primary requirement of biomaterials
is a modulus equal to that of cortical
bones. Because the moduli of α- and α +
β-type titanium alloys are greater than
those of β-type titanium alloys and are
much greater than the moduli of cortical
bones, β-type titanium alloys are, in gen-
eral, desirable for use in low-modulus
biomedical metallic materials. However,
α + β-type titanium alloys are useful
for applications such as bone plate,
which requires a greater modulus of elas-
ticity.
ALLOY DESIGN
In developing a biomedical alloy, non-
toxic elements must be selected as alloy-
ing elements. The cytotoxicity and bio-
compatibility of pure metals and some
metallic biomedical alloys as reported
by Steinemann and Kawahara are com-
Ti
■ monly referenced in the selection pro-
BIOMEDICAL TITANIUM
ALLOYS
Ti-Nb-Ta-Zr and Ti-Nb-Ta-Sn system
alloys are common in both α + β- and β-
type biomedical titanium alloys. The α +
β-type titanium alloys are Ti-15Sn-4Nb-
4Ta-0.2Pd-0.2O-0.05N and Ti-15Sn-4Nb-
2Ta-0.2Pd-0.2O-0.005N.5 These alloys
exhibit high strength, high elongation,
and, in particular, excellent fatigue
strength in a simulated body environ-
1
2
3
4
5
6

In cess (Figure 1).1,2 Elements that are likely 7

1.4 Ni Pd ■ Sn
■ ■ Ta Zr ■ to cause allergic problems, such as nickel,
8
1.2
■■■ ■ chromium, and cobalt, are avoided. Can-
Control: Glass Au Cr ■ Si didates for alloying include Nb, Zr, Ta, 9
1.0
Ag Al Mo, and Sn; the first three are considered
Toxic

0.8 ■ ■ the most suitable elements.

▲ Bi
0.6 ■ Alloy compositions using nontoxic el- Figure 2. The moduli of various biomedical
■ ements are effectively determined using titanium alloys. The dotted patterns represent
Fe Co as-solutionized; the slashed patterns repre-
0.4 ■ the d-electron alloy design method,
Sr sent aged after solutionizing. Here, 1 repre-
0.2 Mg V, Cu, Zn based on electron theory.3 The average
Mo? sents Ti-6Al-4V, 2 is Ti-13Nb-13Zr, 4 is Ti-
■
● Cd, Hg Toxic bond order ( Bo ) between titanium and
16Nb-13Ta-4Mo, 5 is Ti-29Nb-13Zr, and the
▲

0 ● ■
▲

alloying elements and the average d- remaining alloys are Ti-29Nb-13Zr-M, where
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 orbital energy level ( Md ) of titanium M is 4.6Zr (3), 4Mo (6), 2Sn (7), 4.6Sn (8), and
Relative Growth Rate of L929 Cells with alloying elements can be calculated 6Sn (9).
a in this way. Bo is a measure of the cova-
lent bond strength between titanium and
Polarization Resistance (R/Ωm)

Capsule alloying elements; Md correlates with

104 Co-Cr Alloy the electronegativity and the radius of
316L elements. The Bo and Md values calcu-
103 Zr
Ti lated on conventional titanium alloys
304L Nb
102
Toxic Ta gives a Bo- Md map, where α-, α + β-,
Pt
Ag Vital and β-type titanium regions are clearly
100 V Au defined (Table I).4 According to the type
Ni of titanium alloy expected, Bo and Md
Cu Al Mo
10–1 values can be determined, from which
Fe
Co the alloys’ chemical compositions can be
determined. If another factor (e.g., modu-
▲

Biocompatibility
b lus of elasticity) must be taken into ac-
Figure 1. The biological safety of metals de-
count, the modulus of each alloy ap-
termining (a) the cytotoxicity of pure metals parent is described at the point of each
and (b) the relationship between polarization alloy in the map, and the trend of moduli Figure 3. L929 cell viability in extracts of pure
resistance and biocompatibility of pure met- with Bo and Md values will also be titanium, Ti-6Al-4V, and Ti-29Nb-13Ta-4.6Zr
als, Co-Cr, and stainless steels. defined. as evaluated by neutral red assay.

32 JOM • June 1999


ment. Good corrosion resistance and low
cytotoxicity are also reported. A typical
β-type titanium alloy developed for
biomedical applications is Ti-15Mo-5Zr-
3Al, which has been basically developed
as a structural titanium alloy.6
Most recently proposed were low-
modulus, β-type alloys Ti-29Nb-13Ta,
Ti-29Nb-13Ta-4.6Zr, Ti-16~29Nb-13Ta-
4Mo, and Ti-29Nb-2~6Sn.7 R&D on these
new alloys is being organized as a three-
year project supported by the New En-
ergy and Industrial Technology Devel-
opment Organization (NEDO) of the
Ministry of International Trade and In-
dustry, Japan. The moduli of these al-
loys are lower than those of conven-
tional biomedical titanium alloys (Fig-
ure 2), and their tensile properties are
better than or equivalent to those of con-
ventional alloys. Among these alloys,
Ti-29Nb-13Ta-4.6Zr is the most promis-
ing for medical applications.
Powder-metallurgy is convenient for
fabricating these alloys due to the pres-
ence of the high-melting, high-density
elements niobium and tantalum.8 Some
of the powder-metallurgy Ti-Nb-Ta-Zr
system alloys have adequate mechani-
cal properties for biomedical use.
Another type of alloys, Ti-Zr and Ti-
Zr-Nb with high zirconium content (e.g.,
Ti-25~75 Zr and Ti-45~50Zr-0~5Nb, in
at.%), are also being investigated for both
medical and dental applications.9,10 Origi-
nally developed for biomedical applica-
tions, α + β-type Ti-6Al-7Nb is being
investigated for dental applications. The
study on the castability and mechanical
properties of Ti-6Al-7Nb using different
investment materials shows that cen-
trifugal casting using magnesia-based
investment materials provides good
properties.11 Ti-40Zr, Ti-5Al-13Ta, and
(in at.%) Ti-43.1Zr-10.2Al-3.6V are also
candidate for dental applications.12,13
The fracture characteristics of pure-
Table I. The Bo and Md Map
1. Ti-4.5Sn-11.5Mo-6Zr (Beta III)
2. Ti-3Al-8V-4Zr-4Mo-6Cr (Beta C)
3. Ti-3Al-8V-8Mo-2Fe (8-8-2-3)
4. Ti-3Al-13V-11Cr (13-11-3)
5. Ti-15Mo-5Zr-3Al
6. Ti-8Mn (8Mn)
7. Ti-6Al-6Mo-2Sn-4Zr (6-2-4-6)
8. Ti-5Al-2Sn-2Zr-4Mo-4Cr (Ti-17)
9. Ti-6Al-4V (6-4)
10. Ti-6Al-6V-2Sn (6-6-2)
11. Ti-2.25Al-11Sn-5Zr-1Mo-0.2Si (IMI-679)
12. Ti-6Al-0.5Mo-5Zr-0.2Si (IMI-685)
13. Ti-6Al-2Mo-2Sn-4Zr (6-2-4-2)
14. Ti-5Al-6Sn-2Zr-1Mo-0.2Si (IMI-829)
15. Ti-5Al-2.5Sn (A-110)
16. Ti-8Al-1V-1Mo (8-1-1)
a. Ti-Mo
b. Ti-Fe
c. Ti-Cr
d. Ti-Mn
e. Ti-V
f. Ti-Co
g. Ti-Ni
1999 June • JOM
titanium and titanium-alloy dental cast-
ings are also being investigated based on
the fracture mechanics.14
BIOCOMPATIBILITY
The biocompatibility of medical al-
loys is checked by cytotoxicity using
several kinds of cells; the α + β- and β-
type biomedical titanium alloys show
excellent biocompatibility (Figure 3). Ti-
29Nb-13Ta-4.6Zr exhibits better cell vi-
ability as compared with conventional
Ti-6Al-4V. The cell viability of Ti-29Nb-
13Ta-4.6Zr is equivalent to that of pure
titanium.
There are two kinds of surface treat-
ments to improve biocompatibility.15 One
treatment physically forms a thin film of
the highly biocompatible ceramics cal-
cium phosphate (CaP) or hydroxyapa-
tite (HAP) on the surface of the alloys.
The plasma-spray method is most often
used for this treatment,16 although other
methods (e.g., ion plating, radio-fre-
quency magnetron spattering deposi-
tion, or dynamic-ion mixing) are cur-
rently being used for HAP coatings.17,18
The second treatment creates a biocom-
patible layer mainly by chemical reac-
tions without physically making a HAP
thin film on the surface of the alloy.
A surface-coating method using CaP
invert glass was developed in the NEDO
project to create biocompatible ceramics
on the alloys.19 In this method, the pow-
der of CaP invert glass (CaO-P2O5-TiO 2-
Na2O) is coated and heated on the sur-
face of a titanium alloy between 1,073 K
and 1,123 K. Only β-TCP:Ca3 (PO4 )2 ,
which exhibits excellent biocompatibility
with hard tissue, is formed on the sur-
face. Based on x-ray analysis data for the
base glass (CaO-30P2 O5-5TiO2-5Na 2O)
and the coated layer on Ti-29Nb-13Ta-
4.6Zr, only β-TCP can be detected from
the coated layer. A sound-coated layer is
formed when glass is sintered in air;
2.84
2.82 ● Fretting-fatigue strength is affected by
●a
5 ▲ ●1
e ●
Bond Order, Bo
2.80
▲
● 2 3 ■ ▲ ▲▲● ✕ Ti
●● 6 d
2.78 4 ● ● ●▲ f ●
● ■
8 ■ ●●
▲ ■ 97 ■■●● ●●● 11
2.76 g ●●●● ● ●12
■■■ ●
10 ■ ● 14 13
2.74 16 ●●15 ●
2.72
2.25 2.30 2.35 2.40 2.45
d-electron Energy Level, Md
800
700 ●—Air 20 Hz F
600 ▲—Air 20 Hz F
500 ▲ ●—PBS (-) 2 Hz F
Stress Amplitude (MPa)
▲
▲▲▲ ■—Air 20 Hz FF
400 ▲
■ ●▲
▲● ■—PBS (-) 2 Hz FF
▲▲
300 ■■ ■
● ●●
▲
●▲
● ●
▲
▲
200 ■■ ■ ■
■
■■
■■
■
■ ■
■
▲▲
■
■ ■
100
104 105 106 107 108
Cycles to Failure (Nf)
Figure 4. The S-N curves of aged-after-
solutionizing Ti-6Al-4V alloy in air and
PBS (-). F and FF indicate ordinary fatigue
and fretting fatigue, respectively.
when glass is sintered in vacuum, crack-
ing occurs in the coated layer.
Sodium-titanate hydrated gel is
formed on the surface of biomedical tita-
nium alloys when the alloys are im-
mersed in an NaOH solution. Upon heat-
ing, the sodium-titanate hydrated gel is
changed into sodium titanate. HAP is
then formed by the reaction between
body fluid and sodium titanate.20
Calcium can be formed on the surface
of the alloys by dipping the alloys into a
solution containing Ca2+. HAP precipi-
tation on the alloy surface is accelerated
in body fluid by the calcium-containing
oxide film.21 A calcium-ion implanted
surface composed of calcium titanate
and calcium oxide can also be formed on
the surface, with calcium hydroxide ex-
isting on the outer surface of the cal-
cium-ion implanted surface. The pre-
cipitation of CaP is accelerated when the
calcium-ion planted surface is immersed
into body fluid.22
N-ion implantation on the surface of
biomedical titanium alloys to improve
wear resistance is also being investi-
gated.23
FRETTING FATIGUE
Fretting-fatigue characteristics repre-
sent another important consideration.
Fretting-fatigue and ordinary-fatigue
results on biomedical Ti-6Al-4V in air
and simulated body environment: phos-
phate-buffered saline (PBS) (-) solution
are shown in Figure 4.24
the friction coefficient between speci-
men and pad, the contacted area rough-
ness, and sliding distance. In biomedical
Ti-6V-4Al, fretting-fatigue strength is less
than ordinary-fatigue strength in both
air and PBS (-) solution; the ordinary-
fatigue strength of the alloy shows no
difference in air and in PBS (-) solution.
The fretting-fatigue strength of biomedi-
cal Ti-6V-4Al, however, is smaller at in-
2.50 termediate stress amplitude and greater
at high- and low-stress amplitude.
References
1. S.G. Steinemann, “Corrosion of Surgical Implants—in
Vivo and in Vitro Tests,”Evaluation of Biomaterials, ed. G.D.
33
Winter, J.L. Leray, and K. de Groot (New York: Wiley, 1980),
pp. 1–34.
2. H. Kawahara, “Cytotoxicity of Implantable Metals and
Alloys,” Bull. Japan Inst. Metals, 31 (12) (1992), pp. 1033–1039.
3. N. Yukawa et al., “Alloy Design of Superalloys by the d-
electron Concept,” Proc. High Temperature Alloys for Gas
Turbines and Other Applications (Belgium: Commission of
European Communities, 1986), pp. 1–9.
4. M. Morinaga, N. Yukawa, and H. Adachi, “Electronic
Structure and Phase Stability of Titanium Alloys,” J. Iron and
Steel Inst. Japan, 72 (6) (1986), pp. 555–562.
5. Y. Ito et al., “New Titanium Alloys for Medical Implants,”
Proc. Titanium’95: Science and Technology, ed. P.A. Blenkinsop,
W.J. Evans, and H.M. Flower (London: IOM, 1995), pp. 776–
1783.
6. Y. Okazaki et al., “Mechanical Properties and Corrosion
Fatigue of New Titanium Alloys for Medical Implants in
Physiological Saline Solution,” J. Japan Inst. Metals, 59 (10)
(1995), pp. 1078–1085.
7. M. Niinomi et al., “New β-Type Titanium Alloys with
High Biocompatibility,” Non-Aerospace Applications of Tita-
nium, ed. F.H. Froes, P.G. Allen, and M. Niinomi (Warrendale,
PA: TMS, 1998), pp. 217–223.
8. S. Yoshitani et al., “Mechanical Properties of β-Type Alloys
with High Biocompatibility Fabricated by Powder Metal-
lurgy Processing,” CAMP, ISIJ, 12 (1) (1999), p. 540.
9. E. Kobayashi et al., “Evaluation of Mechanical Properties
of Dental Casting Ti-Zr Based Alloys,” J. Japanese Soc. Dental
Materials and Devices, 14 (3) (1995), pp. 321–328.
10. E. Kobayashi et al., “Alloy—Design of Titanium-Zirco-
nium Based Alloys Containing Niobium as Biomedical Ma-
terials,” Proc. Fifth World Biomaterials Congress (Toronto,
Canada: Univ. of Toronto Press, 1996), pp. 481–482.
11. E. Kobayashi et al., “Castability and Mechanical Proper-
ties of Ti-6Al-7Nb Alloy Dental-Cast,” J. Japanese Soc. Dental
Materials and Devices, 14 (4) (1995), pp. 406–413.
12. K. Kato et al., “On the Adhesiveness between Ti-40wt%Zr
Alloy and the Thermosetting Facing Resin,” J. Japanese Soc.
Dental Materials and Devices, Special Issue 33, 18 (1999), p. 121.
13. H. Hamanaka et al., “Corrosion Resistance and Mechani-
cal Properties of Cast Ti-5Al-13Ta Alloys,” J. Japanese Soc.
Dental Materials and Devices, Special Issue 31, 17 (1998), p. 88.
14. K. Narita et al., “Fracture Toughness Characteristic of
Cast Pure Titanium and Titanium Alloy,” J. Japanese Soc.
Dental Materials and Devices, Special Issue 31, 17 (1998), p. 90.
15. E. Kobayashi et al., “Structure Control of Ti–Zr Biomedi-
cal Implant Alloys,” J. Japanese Soc. Dental Materials and
Devices, Special Issue 26 (1995), pp. 78–79.
16. T. Hanawa, “Surface Modification of Metallic Bio-mate-
rials,” Materia Japan, 37 (19) (1988), pp. 853–855.
17. M. Yoshinari, K. Ozeki, and T. Sumii, “Properties of
Hydroxyapatite-Coated Ti-6Al-4V Alloy Produced by the
Ion-Plating Method,” Bull. Tokyo Dent. Coll., 32 (1991), pp.
147–156.
18. M. Yoshinari et al., “Influence of Rapid Heating with
Infrared Radiation on RF Magnetron Sputtered Calci-
um Phosphate Coatings,” J. Biomed. Mater. Res., 37 (1997), pp.
60–67.
19. T. Kasuga and Y. Abe, “Calcium Phosphate Invert Glass-
es with Soda and Titania,” J. Non-Crystalline Solids, 243
(1999), pp. 70–74.
20. H.–M. Kim et al., J. Biome. Mater. Res., 34(1996), p.409.
21. T. Hanawa et al., “Surface Modification of Titanium in
Calcium-Ion-Containing Solutions,” J. Biomed. Mater. Res., 34
(1997), p. 273.
22. T. Hanawa, S. Kihara, and K. Murakami, ASTM STP 1196
(1994), pp. 170–184.
23. S. Fukumoto et al., Abstract Booklet of Xi’an Int. Titanium
Conf. (1998), p. 84.
24. N. Maruyama, T. Kobayashi, and M. Sumita, “Fretting
Fatigue Strength of a Ti-6Al-4V Alloy in a Pseudo-Body-
Fluid and Quantitative Analyses of the Substances in the
Fluids,” J. Japanese Soc. Biomaterials, 13 (1) (1995), pp. 14–20.
Mitsuo Niinomi is with the Department of Production
Systems Engineering at Toyohashi University of Tech-
nology.
For more information, contact M. Niinomi,
Toyohashi University of Technology, 1-1 Hi-
barigaoka, Tempaku-cho, Toyohashi 441-8580,
Japan; telephone 81532-44-6706; fax 81-532-44-
6690; e-mail niinomi@sp-Mac4.tutpse.tut.ac.jp.

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