Topics in Recent Research and Development

of Metallic Biomaterials

Edited from original text of:

Professor Mitsuo Niinomi
Department of Production Systems Engineering,
Toyohashi University of Technology
1-1, Hibarigaoka, tempaku-cho, Toyohashi 441-8580
 Artificial hip joint

Acrylic
Ceramiccement
Head

UHMWP

Metallic
Before stem: Ti
implantation alloys
After
implantation
Bone plate
Bone plate and screws
Universal instrumentation for spinal surgery
 Porcelain glazed metal crown
Attachment post
Inlay

Crown

Fig. Examples of dental

Denture prostheses
 Stainless Steel Vitallium Titanium
Metals

PMMA HDP Cellophane

Plastics
Cuprophane

Al O Bioglass TCP
2 3
Ceramics
Hydroxyapatite

1920 1930 1940 1950 1960 1970 1980

Year

Fig. History of metals, plastics and ceramics for biomedical applications.

Table Biocompatibility of various biomaterials judged by patterns of osteogenesis

Pattern of osteogenesis Biomaterials

Stainless steel, Vitallium,

Intervend osteogenesis PMMA Bio-tolerant materials
(Polymethyl methacrylate)

Titanium, Tianium alloys,

Contact osteogenesis Carbon, Alumina, Zirconia, Bio-inert materials
Titania, TiN, Si3N4

Bioglass, Ceravital,
Bonding osteogenesis Tricalcium phosphate, Bio-active materials
Hydroxyapatite,
A-W glass ceramic
Type of metallic biomaterials and their
topics
Stainless steels for biomedical applications

Co alloys for biomedical applications

Titanium alloys for biomedical applications

Development of low modulus type titanium alloy
composed of non-toxic and non-allergic elements
for biomedical applications
Avoid to add allergic elements:

25

Nickel sensitization in the population, [%]

20

Females under 30
15

10

5
Males under 30

0
84 86 88 90 92 94 96
year

Fig. Frequency of nickel sensitization in the population.

 An example of Ni free stainless steels

Cr Ni Mo Mn N C P S Cu Fe

EU90 15.62 0.120 3.83 16.66 0.810 0.050 0.020 0.004 0.04 bal

16.5-17.5 3-3.5 10-12 0.8-1.2 bal

Stainless steel for electrode of FES (Functional
Electrical Stimulation

22.0 Cr, 10% Ni, 6.02% Mn, 2%mo, 0.41% N

and bal. Fe
 : SUS316L
: NAS604PH No failure > 107
: NAS106N

N / 104 6

0
0 2 4 6 8 10
d / mm
Fig.12 Relationship between number of rotation of electrode materials
to failure, N, and distance between chucks, d, by a dual-driven
rotating-bending failure method in air.
 (a) SUS316L
0.10
0.08

CNi / ppm
0.06
0.04
0.02
0
0 5 10 15 20 25
Time, t / hrs.
(b) NAS604PH
0.10
0.08
CNi / ppm

0.06
0.04
0.02
0
0 1 2 3 4 5
Time, t / hrs.
(c) NAS106N
0.10
0.08
CNi / ppm

0.06
0.04
0.02
0
0 20 40 60 80 100 120 140
Time, t / hrs.

Fig. Nickel concentration, Cni during dual-driven rotating-bending failure test in saline at 310K.
New process for making Ni (Mn) free stainless steel
Improvement of workability of Ni free austenitic stainless
steel with high nitrogen (Hanawa and Kuroda et al.)

Fe-24Cr-2Mo ferritic stainless steel

Grain refinement by
thermo-mechanical treatment

Fabricating wire making final shape

before adding nitrogen

Heating in nitrogen gas

Ni (and Mn) free austenite stainless wire

Co alloys for biomedical applications
Co base alloy

(1) Ni free Co base alloy: Co-28Cr 6Mo (mass %)

ASTM F799
Microstructural control (Chiba et al.)
(2) Co-Cr-Mo alloy:
Forged high C Co-Cr-Mo alloy
fabricated through vacuum induction
melting, electroslag remelting, press and
precision forging, and rolling gives good
wear resistance and fatigue strength.
(meet the requirement of ASTM 1537 warm
worked Co-Cr-Mo alloy)
Co base alloy

(3) Martensite transformation in Co-Cr -Mo alloy

Metastable fcc phase in low carbon Co-Cr-Mo

alloy transforms into hcp martensite by
deformation, aging or quenching showing wear
resistance.

(4) Dispersion strengthened Co-Cr-Mo alloy

(ASTM F-799)
Small amount of oxides forming elements,
La and Al
Co base alloy

(5) MIM (Metal Injection Molding)

Co-Cr-Mo alloy can be fabricated by MIM

and shows good mechanical properties and
fatigue properties.
Titanium alloys for biomedical applications
The usage of titanium and its alloys for medical
and dental implants is rapidly increasing because of

Good biocompatibility

Good corrosion resistance

High specific strength

Good balance of mechanical properties

etc.
 TABLE
Titanium alloys for biomedical applications

1. Pure Ti (ASTM F67-89) 9.Ti-13Nb-13Zr (ASTM F1713-96) : near type

Grade 1, 2, 3 and 4 (U.S.A.),Low modulus
Purity Increase (add N, Fe and O) 10.Ti-12Mo-6Zr-2Fe (ASTM F1813-97): type
Strength Increase (U.S.A.), Low modulus
Ductility Decrease 11.Ti-15Mo : type (U.S.A.), Low modulus
2. Ti-6Al-4V ELI (ASTM F136-84, F620-87) : + 12.Ti-16Nb-10Hf : type (U.S.A.), Low modulus
type 13.Ti-15Mo-5Zr-3Al : type (Japan), Low modulus
3. Ti-6Al-4V (ASTM F1108-88) : + type 14.Ti-15Mo-2.8Nb-0.2Si-0.26O : type (U.S.A.), Low
4.Ti-6Al-7Nb (ASTM F1295-92, ISO5832-11 modulus
: + type Swiss 15.Ti-35Nb-7Zr-5Ta : type (U.S.A.), Low modulus
5. Ti-5Al-2.5Fe (ISO5832-10) : + type 16.Ti-29Nb-13Ta-4.6Zr : type (Japan), Low modulus
Germany 17.Ti-40Ta, Ti-50Ta : type (U.S.A.), High corrosion
6. Ti-5Al-3Mo-4Zr : + type (Japan) resistance
7. Ti-15Sn-4Nb-2Ta-0.2Pd : + type (Japan)
8. Ti-15Zr-4Nb-2Ta-0.2Pd : + type (Japan)

Developed for biomedical applications

Why type titanium alloys

type titanium alloys composed of non-toxic and
non-allergic elements are getting much attention
because of their low modulus of elasticity more
similar to that of bone comparing with and +
type titanium alloys and other representative
metallic biomaterials:
Modulus / GPa

250

200

150

100

50

0
UHMW

FIGURE
PMMA Bone Cement
Polyethylene

Bone

Elastic moduli of UHMW polyethylene, PMMA bone cement,

bone, Ti-6Al-4V, 316L stainless steel and Co-Cr-Mo alloy.
Ti-6Al-4V

316L Stainless Steel

Co-Cr-Mo Alloy
Low modulus of elasticity nearer to that of bone:

Good stress transmission between implant and bone

Good for healing of bone fracture

Good bone remodeling

Remodeling of Bone:
PIEZOELECTRICITY OF BONE
Electrical polarization by strain
Piezoelectricity induces bone remodeling, the
concept proceeded to electrical callus in fracture
treatment. (I. Yasuda, 1977)
Load

+ -
+ -
+ - Bone Bone
Absorption
Absorption Formation
Development of low modulus type titanium alloy
composed of non-toxic and non-allergic elements
for biomedical applications
Target of development
Important factors for each part of
artificial hip joints

Cortical bone Cup Head Stem

Imframatiory Biocompatibility Biocompatibility Biocompatibility
Loosening Dissolution Wear resistance Wear resistance Corrosion resistance
of ion
Corrosion High hardness High hardness High strength
Formation of
Cup wear debris Deformation resistance Low modulus
Head
Fracture of stem
Long term
usage in Aim of investigation
living body Fracture
Stem of bone Development of fabrication process of titanium
Bone alloys , which have superior biocompatibility
absorption and can be used for long term

Direction of development
Superior biocompatibility and reliability of mechanical properties
Non-toxic elements High strength Long fatigue life High wear resistance High corrosion resistance
Superior adhesiveness with bone Low modulus similar to that of bone High workability
 Good biocompatibility
(+) type High strength
titanium alloysGood corrosion resistance type
titanium
High cold workability
alloys
Low modulus
Low modulus

Selection of non-toxic elements

Selection of stabilizing elements

Approval by Ministry of Health, Labor and Welfare

Alloy design uisng d-electron alloy
deign method

Fabrication of designed alloys

Laboratory size ingot making
of designed alloys
Practical size ingot making
of designed alloys

Evaluation of mechanical properties

Tensile tests, Modulus measerments,
measerments,
Fatigue tests, etc.
Surface modification
Evaluation of dental precision castability

Practical use
tests
Clinical
Evaluation of precision machinability
Cyto-
Cyto-toxicity tests Animal tests

Evaluation of practical instrumentations

Selection of alloying elements:
Coefficient of fibroblastic outgrowth

1.8 Ti
1.6 In

Polarization resistance , R
Ni Pd Sn
1.4 Zr
Ta Capsule
1.2 Control : Glass 10 4 Co-Cr alloy
Au Cr Si
1.0 Al 10 3 316L
Toxic

Ag
TiZr
0.8 Bi 10 2
Toxic 304L Nb
0.6 PtTa
Ag
Fe Co 10 0 V Au
Vital
0.4 Sr Ni
Mg V,Cu,Zn 10 -1 Cu AlMo
0.2 Toxic Mo ? Co Fe
Cd,Hg
0 Biocompatibility /
0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
Fig. Relationship between polarization
Relative growth rate of L-929 cells
resistance and biocompatibility of
Fig. Cyto-toxicity of pure metals: pure metals, Co-Cr alloy and
Only relative growth rate of L-929 stainless steels, SUS 316L and SUS
cells for Mo. 304L.
Avoid to add allergic elements:

25

Nickel sensitization in the population, [%]

20

Females under 30
15

10

5
Males under 30

0
84 86 88 90 92 94 96
year

Fig. Frequency of nickel sensitization in the population.

 Au Cd
Zn
Pt 1.8% 1.5% Sb
1.8%
Cu 3.6% 0.4%
11.3%

Hg

Cr 23.0%

9.5%
Ni
Pd
13.5%
11.3%
Sn Co
12.8% 13.5%

Fig. Percentage of metal allergy caused by each alloy.

Ti-Nb-Ta-Zr
EXPERIMENT 1: BIOCOMPATIBILITY TEST

5x10 mm

Implantation of columnar
specimen into lateral femoral
condyle under intravenous
anesthesia.
RESULT 1: 8 WEEKS AFTER IMPLANTATION
C.M.R.

Direct Direct Lucent line

TiNTZ Ti6Al4V SUS316L
Regarding biocompatibility, TiNTZ is equal to
or possibly grater than Ti6Al4V both showing
direct contact, and much better than SUS316L
with a radio lucent line.
Evaluation of bone formation versus low modulus
EXPERIMENT 2: INTRAMEDULLARY FIXATION
Experimental fracture
of the tibia
1.
Keeping
Fibula intact
Longitudinal drilling

2. 3.

Sawing Tibia Driving metal rod

 EXPERIMENT 2: X-RAY OBSERVATION

X-ray pictures were taken at every 2weeks for

24 weeks, and the states of fracture healing,
remodelling and atrophy were investigated.
0W 2W 4W 6W 8W 10W 12W 14W 16W 18W 20W 22W
(a) Ti-29Nb-13Ta-4.6Zr

0W 2W 4W 6W 8W 10W 12W 14W 16W 18W 20W 22W

(b) Ti-6Al-4V ELI

0W 2W 4W 6W 8W 10W 12W 14W 16W 18W 20W 22W

(c) SUS 316L

Healing state of bone fracture up to 22 weeks after implantation

Remodeling at 24 weeks after
implantation

Bone absorption

Bone
formation

TiNTZ Ti6Al4V SUS316L

RESULT 2: C.M.R. CROSS SECTION AT 24W

Newly formed
cortical bone

TiNTZ Ti6Al4V SUS316L

 C.M.R.

X-P

Fuchsine
Fuchsine
TNTZ Ti-6Al-4V ELI SUS316L

Fig. Crosss section of tibia at 24 weeks after implantation

 Three point bending tests
(Mechanical evaluation of bone absorption)

3x80 mm
Preparation of three point bending tests
Taking X ray photo.
photo.,, Taking out tibia, Cutting far end
of tibia, Pulling out intramedullary rod, Cutting of
intact,, Three point bending test
fibula intact
 Three point bending tests: fracture
load
Implanting period: 16-18 months (except one died at 43
weeks)
TiNTZ(n=3) Ti6Al4V(n=3) SUS316L(n=3)
kgf
80
+19.4
+19.4

60 -15.0
-15.0
-0.2
-0.2 -12.5
-12.5
+9.2
+9.2
+13.2 -8.5
-8.5 -9.1
+13.2 -9.1
40
died at
+10.5
+10.5
43 weeks43

20
Subject
Subject side
side Intramedullary IntramedullarySublect
Intramedullary Subject side Intramedullary Sublect side
side Intramedullary
Intramedullary
rod side
rod side rod side
rod side rod
rod side
side
X ray photo. Implanting period: 18 months

51.5kg > 46.8kg 60.4kg < 72.1kg

SUS316L (-9.1%) TiNTZ (+19.4%)

 Stems and heads for
sheep

22 , 24, 26
S size (Neck offset: -2, 0, +2 mm)

M size (Neck offset: -2, 0, +2 mm) L size (Neck offset: -2, 0, +2 mm)
 X-ray photo. after implantation
and breading with load releasing

Just after implantation

front view: - side view: -
3 weeks after
implantation
 Observation of
progress

2 weeks after 10 weeks after 28 weeks after

implantation implantation implantation
 Recently reported low Youngs modulus type titanium
alloys for biomedical applications
Ti-Fe-Ta system alloy Kuroda et al.

Ti-Zr-Nb-Ta system alloy(for example,Ti-40Zr-10Nb at%)alloy

:40GPa (Inoue et al.)

Ti-Mo-Mn-Nb-Zr system alloy, Ti-Fe-Mo-Mn-Nb-Zr system alloy

X. P. Zhang et al.
Porous titanium for biomedical applications
Pure titanium, Ti-6Al-4V, Ti-15Mo-5Zr-3Al (Hanada et al.

Porous titanium based composite for biomedical applications

Ti-TiC Kanetake et. al.
 Strengthening
with keeping low Youngs modulus
Youngs modulus of Ti-29Nb-13Ta-4.6Zr

Modulus of Elasticity,E / GPa 120

100

80

(c) ST + 573K, 259.2ks

(d) ST + 598K, 259.2ks

(e) ST + 673K, 259.2ks

(g) ST + 813K, 14.4ks

(f) ST (1123K, 3.6ks)
60
(b) ST (1063K, 3.6ks)
(a) As-rolled plate

40

20

0
Ti-29Nb-13Ta-4.6Zr Ti-6Al-4V ELI
Youngs moduli of Ti-29Nb-13Ta-4.6Zr and conventional Ti-6Al-4V ELI
for biomedical applications.
Ti-29Nb-13Ta-4.6Zr show excellent mechanical properties
and low modulus
 30

1600
25

Tensile strength, B / MPa

Elongations, P (%)
1200 20

15
800

10

400 B P B P
As-ST As-CR 5
ST-598K CR-598K
ST-673K CR-673K
0 0
40 50 60 70 80 90 100 110 120
Youngs modulus, E/GPa
Figure Relationships between tensile strength, elongation and Youngs modulus of
Ti-29Nb-13Ta-4.6Zr conducted with each heat treatment. ST: solution treatment,
CR: cold rolling, ST-598 K: aged at 598 K for 259.2 ks after ST, ST-673 K: aged
at 598 K for 259.2 ks after ST , CR-598 K: aged at 598 K after CR for 259.2 ks,
CR-673 K: aged at 673 K for 259.2 ks after CR.
 1000 200
180
0.2% Proof Stress, 0.2 / MPa B

Youngs Modulus, YG / GPa

Reduction of Area, ( %)
Tensile Strength, B / MPa
800 160

Elongation, El (%)
140
0.2
600 120
100
400 80
60
YG
200 40
El
20
0 0
0 20 40 60 80 100
Cold Work Ratio / %
Figure Tensile properties of cold swaged bar as a function cold
working ratio.
Creating super elasticity
Functions

Shape memory
Super elasticity
etc
TiNi
TiNi Stent
Stent (Partially
(Partially Deployed)
Deployed)
Material: TiNi

Design drivers:
Shape memory effect

Bio-compatible

Blood compatible
 Ni is high risk element for allergy

Ni free shape memory / super elastic

titanium alloys for biomedical applications

Ni free type titanium alloys

Superelastic Beta TiMo Alloy for Biomedical Applications
(Stress induced Martensite)

Ti-9.7Mo-4Nb-2V-3Al (M. H. Wu et al.)

 Other metallic materials expected for
biomedical applications

(1) Ta, Nb

(2) Amorphous alloys

Greater strength, greater corrosion resistance

and lower Youngs modulus

Zr-7.6Ni-12.3Cu-3.5Al (mass%)
Zr-11Ti-13.2Cu-10Ni-3.7Be (mass%)
Co-Fe-Cr-Si-B system alloy
Co-20%P (mass%)
Co-Cr-C system alloy
(3) Mg alloy

Low Youngs modulus

99.9999 mass% Mg shows excellent corrosion

resistance

Application for dental biomaterials for denture and

crowns
Thank you for your attention