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Culture Documents
A R T I C L E I N F O
A B S T R A C T
Article history:
Available online 9 November 2014
Human tissue is structured mainly of self-assembled polymers (proteins) and ceramics (bone minerals),
with metals present as trace elements with molecular scale functions. However, metals and their alloys
have played a predominant role as structural biomaterials in reconstructive surgery, especially
orthopedics, with more recent uses in non-osseous tissues, such as blood vessels. With the successful
routine use of a large variety of metal implants clinically, issues associated with long-term maintenance
of implant integrity have also emerged. This review focuses on metallic implant biomaterials, identifying
and discussing critical issues in their clinical applications, including the systemic toxicity of released
metal ions due to corrosion, fatigue failure of structural components due to repeated loading, and
wearing of joint replacements due to movement. This is followed by detailed reviews on specic metallic
biomaterials made from stainless steels, alloys of cobalt, titanium and magnesium, as well as shape
memory alloys of nickeltitanium, silver, tantalum and zirconium. For each, the properties that affect
biocompatibility and mechanical integrity (especially corrosion fatigue) are discussed in detail. Finally,
the most critical challenges for metallic implant biomaterials are summarized, with emphasis on the
most promising approaches and strategies.
2014 Elsevier B.V. All rights reserved.
Keywords:
Metallic biomaterials
Biocompatibility
Corrosion
Mechanical properties
Medical devices
Contents
1.
2.
3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Historical development of metallic biomaterials. . . . . . . . . . . . . . . . . . . . . .
1.1.
1.2.
Denitions of biomedical materials, biomaterials and biological materials .
Denition of biocompatibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.3.
1.4.
Classication of medical devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Essential considerations in design of metallic biomaterials. . . . . . . . . . . . . . . . . . .
Biocompatibility of elements and selection of alloying elements. . . . . . . . .
2.1.
Corrosion of implant materials in the body. . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
2.3.
Mechanical working conditions in the human body . . . . . . . . . . . . . . . . . . .
Wear of joint implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Osseo-integration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.
2.6.
The objectives of the rest of the review article . . . . . . . . . . . . . . . . . . . . . . .
Stainless steels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Alloying chemistry: corrosion resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Biocompatibility of alloying elements used in stainless steels . . . . . . . . . . .
3.2.
3.2.1.
Iron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chromium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.2.
Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.3.
Biocompatibility of 316L stainless steel. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.
Mechanical properties of implant-grade stainless steels . . . . . . . . . . . . . . .
3.4.
General mechanical properties . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.4.1.
* Corresponding author.
E-mail address: qzchen202@gmail.com (Q. Chen).
http://dx.doi.org/10.1016/j.mser.2014.10.001
0927-796X/ 2014 Elsevier B.V. All rights reserved.
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3
3
3
5
5
5
6
7
7
9
10
10
10
11
12
12
12
12
13
13
13
4.
5.
6.
7.
8.
9.
3.4.2.
Fatigue properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Medical applications of stainless steels . . . . . . . . . . . . . . . . . . . . . . . . .
3.5.
Current issues and challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.6.
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.7.
Cobalt-based alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alloying chemistry: corrosion resistance . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Biocompatibility of alloying elements: Co, Mo and W . . . . . . . . . . . . .
4.2.
Cobalt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.1.
4.2.2.
Molybdenum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tungsten . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.3.
Biocompatibility of cobalt alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
4.4.
Mechanical properties of medical-grade cobalt alloys . . . . . . . . . . . . .
General mechanical properties . . . . . . . . . . . . . . . . . . . . . . . .
4.4.1.
Fatigue properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.4.2.
Medical applications of cobalt alloys . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.5.
4.6.
Current issues and challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.7.
Titanium alloys used as orthopedic implants . . . . . . . . . . . . . . . . . . . . . . . . . .
Alloying chemistry: microstructure design . . . . . . . . . . . . . . . . . . . . . .
5.1.
5.2.
Grading and classication of titanium and its alloys . . . . . . . . . . . . . .
Biocompatibility of alloying elements . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.
Titanium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.1.
Vanadium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.2.
5.3.3.
Aluminum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Niobium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.3.4.
Biocompatibility of titanium alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.4.
Microstructure and general mechanical properties . . . . . . . . . . . . . . . .
5.5.
a titanium alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.5.1.
ab titanium alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.5.2.
b titanium alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.5.3.
Fatigue properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.6.
Wear resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.7.
Bone bonding mechanisms of Ti alloys . . . . . . . . . . . . . . . . . . . . . . . . .
5.8.
Clinical applications of titanium alloys . . . . . . . . . . . . . . . . . . . . . . . . .
5.9.
5.10. Current issues with titanium alloys as implant biomaterials . . . . . . . .
5.11. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stainless steels, cobalt and titanium alloys in total joint replacement . . . . . .
Historical perspective of the development of total joint replacements
6.1.
Materials used in total joint replacements . . . . . . . . . . . . . . . . . . . . . .
6.2.
Current issues and challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.3.
Magnesium alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Three generations of biomaterials in terms of clinical outcomes . . . . .
7.1.
Rationale of developing Mg-alloys as medical implants . . . . . . . . . . . .
7.2.
Corrosion of Mg alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.3.
Metallurgical roles of alloying elements in magnesium alloys . . . . . . .
7.4.
Biocompatibility and toxicity of alloying elements in Mg alloys . . . . .
7.5.
Magnesium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.1.
Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.2.
Manganese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.3.
Copper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.4.
Zinc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.5.5.
Mechanical properties of Mg-alloys . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.6.
MgZn-based alloys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.6.1.
MgCa-based alloys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.6.2.
Potential applications and challenges of magnesium alloys . . . . . . . . .
7.7.
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.8.
NiTi shape-memory alloys [102] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Corrosion of NiTi alloy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.
8.2.
In vitro evaluation of biocompatibility of NiTi alloy . . . . . . . . . . . . . . .
In vivo evaluation of biocompatibility of NiTi in animal models . . . . .
8.3.
In vivo trials of NiTi implants in human [409] . . . . . . . . . . . . . . . . . . .
8.4.
Biocompatibility of NiTi wires as stents (lters) . . . . . . . . . . . . . . . . . .
8.5.
8.6.
Current and potential applications of NiTi . . . . . . . . . . . . . . . . . . . . . .
Self-expandable stents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.6.1.
Orthopedic and orthodontic applications . . . . . . . . . . . . . . . .
8.6.2.
8.7.
Mechanical properties of NiTi alloy [43] . . . . . . . . . . . . . . . . . . . . . . . .
General mechanical properties . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1.
8.7.2.
Fatigue properties of NiTi alloys . . . . . . . . . . . . . . . . . . . . . . .
Issues and challenges of NiTi implants . . . . . . . . . . . . . . . . . . . . . . . . .
8.8.
8.9.
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Tantalum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Corrosion and biocompatibility of tantalum . . . . . . . . . . . . . . . . . . . . .
9.1.
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13
14
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17
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21
21
22
22
22
22
23
23
23
23
24
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24
24
25
25
26
26
26
27
29
29
29
30
30
31
33
34
34
35
36
37
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38
38
38
38
38
38
39
39
40
40
41
41
43
44
45
45
46
48
48
48
48
48
49
49
10.
11.
12.
13.
14.
9.2.
Clinical applications of tantalum . . . . . . .
Zirconium alloys . . . . . . . . . . . . . . . . . . . . . . . . .
10.1. Corrosion of zirconium . . . . . . . . . . . . . . .
10.2. Biocompatibility of zirconium . . . . . . . . .
10.3. Clinical application of zirconium alloy. . .
Silver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11.1. Biocompatibility of silver . . . . . . . . . . . . .
11.2. Medical application of Ag . . . . . . . . . . . . .
Metals used as medical electrodes . . . . . . . . . . .
Metallic materials used in orthodontic implants
Summary and remarks . . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction
1.1. Historical development of metallic biomaterials
The use of metallic materials for medical implants can be traced
back to the 19th century, leading up to the era when the metal
industry began to expand during the Industrial Revolution [1]. The
development of metallic implants was primarily driven by the
demands for approaches to bone repair, typically internal fracture
xation of long bones. However, almost no attempts of implanting
metallic devices, such as spinal wires and bone pins made from
iron, gold or silver, were successful until Listers aseptic surgical
technique was implemented in the 1860s [1]. Since then, metallic
materials have predominated in orthopedic surgery, playing a
major role in most orthopedic devices, including temporary
devices (e.g. bone plates, pins and screws) and permanent implants
(e.g. total joint replacements) [2]. Concurrently, metals also found
applications in dental and orthodontic practice, including tooth
llings and roots [3]. Recently, increasing research effort in
metallic biomaterials has been invested in application of the nonconventional reconstructive surgery of hard tissues/organs, such as
the application of NiTi shape memory alloys as vascular stents [4]
and the development of new magnesium-based alloys for bone
tissue engineering and regeneration [5].
Despite the large number of metals and alloys able to be
produced in industry, only a few are biocompatible and capable of
long-term success as an implant material. These form components
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50
50
50
50
50
51
51
51
51
51
52
52
52
Table 1
Four categories of metallic biomaterials and their primary applications as implants.
Type
Primary utilizationsa
Status of applications
Ref.
Stainless steels
1. Temporary devices (fracture plates, screws, hip nails, etc.) (Class II)
2. Total hip replacements (Class II)
Routinely applied
[9]
Co-based alloys
Routinely applied
[9]
Ti-based alloys
Routinely applied
[9]
1.
2.
3.
4.
5.
6.
7.
FDA approved
FDA approved
FDA approved
FDA approved
Research
FDA approved
FDA approved
[10]
Miscellaneous others
NiTi
Mg
Animal trial
[11,12]
Ta
FDA approved
FDA approved
[13]
Fig. 1. (a) The Harrington rod, a stainless steel surgical device. (b) The stem of a total hip replacement, usually made from either stainless steel, cobalt- or titanium-based
alloys.
Fig. 2. (a) A vascular stent and (b) an aneurysm clip, both made from NiTi alloy.
Medical devices are classied by government regulatory authorities, including the FDA, Medical Devices Bureau of Health Canada,
European Commission on Health and Consumers (ECHC) and the
Therapeutic Goods Administration (TGA) [21] (Table 2). Classication of medical devices is based on the complexity of the device, the
level of control necessary to assure its safety and effectiveness, and in
Australia a higher classication is given to devices with increasing
degree of invasiveness, depending on which tissue the device is
applied to (e.g. class III corresponds to chronic implantable devices).
Non-implant (class I and II) medical devices (e.g. surgical and dental
instruments) are manufactured from commercial-grade materials.
These materials adequately meet clinical requirements where
contact with human tissue is transient. Biomaterials of interest to
the scientic community are generally used in medical devices that
fall within the higher classes in Table 2, which must be suitable for
close and prolonged contact with human tissue, and thus require
premarket approval. This review is devoted to those metallic
biomaterials used in FDA class II and III medical devices.
Table 2
Some accepted classications of medical devices [14].
Authority
Class
TGAa
FDAa
ECHCa
Health Canada
I
I
I
I
IIa, IIb
II
IIa
II
III
III
IIb
III
General description
Low
Surgical instruments, mechanical
barriers
Low/moderate
Contact lenses, ultrasound
probes
Restrictions
Health risk
Examples
a
III
IV
Medium to long term contact,
chronic implants, control systems
High
Pacemakers, perfusion pumps,
vascular stents
FDA, Food and Drug Administration (USA); ECHC, European Commission on Health and Consumers (European Union); TGA, Therapeutic Good Administration (Australia).
6
Table 3
Elements in the human body [22].
Element
Ca
Na
Cl
Mg
Trace element
Wt%
At%
65.0
25.5
18.5
9.5
9.5
63.0
3.3
1.4
1.5
0.31
1.0
0.22
0.4
0.06
0.3
0.05
0.2
0.3
0.2
0.03
0.1
0.1
<0.01
<0.01
Table 4
Macro elements and their roles in the human body [23].
Macro elements
Roles
O, C, H, N
Ca
P
Mg
Na
K
Cl
S
Table 5
Some trace elements (also called micronutrients) and their roles in the human body.
Trace elements
Roles
Fe
Contained in heme groups of hemoglobin and myoglobin which are required for oxygen transport in the body, as well as many other metabolic
enzymes and FeS proteins. Part of the cytochrome p450 family of enzymes. Anemia is the primary consequence of iron deciency. Excess iron
levels can enlarge the liver, may provoke diabetes and cardiac failure. The genetic disease hemochromatosis results from excess iron
absorption. Similar symptoms can be produced through excessive transfusions required for the treatment of other diseases.
Contained in enzymes of the ferroxidase system which regulates iron transport in the blood and facilitates release from storage. A structural
element in the enzymes tyrosinase, cytochrome c oxidase, ascorbic acid oxidase, amine oxidases, and the antioxidant enzyme copper zinc
superoxide dismutase, amongst others. A copper deciency can result in anemia from reduced ferroxidase function. Excess copper levels cause
liver malfunction and are associated with genetic disorder Wilsons Disease
Major component of the mitochondrial antioxidant enzyme manganese superoxide dismutase. A manganese deciency can lead to improper
bone formation and reproductive disorders. An excess of manganese can lead to poor iron absorption.
Required for production of thyroxine which plays an important role in metabolic rate. Decient or excessive iodine intake can cause goiter (an
enlarged thyroid gland).
Important for reproductive function due to its role in FSH (follicle stimulating hormone) and LH (leutinizing hormone). Required for DNA
binding of zinc nger proteins which regulate a variety of activities. A component of the enzymes alcohol dehydrogenase, lactic dehydrogenase
carbonic anhydrase, ribonuclease, DNA Polymerase and the antioxidant copper zinc superoxide dismutase. An excess of zinc may cause anemia
or reduced bone formation.
Contained in the antioxidant enzyme glutathione peroxidase and heme oxidase. Deciency results in oxidative membrane damage with
different effects in different species. Human deciency causes cardiomyopathy and is known as Keshans disease.
Contained in vitamin B12. An excess may cause cardiac failure.
Contained in the enzyme xanthine oxidase. Required for the excretion of nitrogen in uric acid in birds. An excess can cause diarrhea and growth
reduction.
A cofactor in the regulation of sugar levels. Chromium deciency may cause hyperglycemia (elevated blood sugar) and glucosuria (glucose in
the urine). Elevated levels of some forms of chromium, such as Cr(VI), can be carcinogenic.
Cu
Mn
I
Zn
Se
Co
Mo
Cr
Chromium
Cobalt
Copper
Iodine
Table 8
The ionic concentrations (mM) of human blood plasma [32].
Iron
Selenium
Lithium
Molybdenum
Nickel
Strontium
Tungsten
Zinc
Table 7
Metal sensitivity.
Ion
+
Na
HCO3
K+
HPO42
Mg2+
Cl
Ca2+
SO42
142.0
4.2
5.0
1.0
1.5
147.8
2.5
0.5
142.0
27.0
5.0
1.0
1.5
103.0
2.5
0.5
10
25
60
debris and cellular material that can result in focal adhesions onto
implants. These uids have a nearly neutral pH value (7.27.4 at
37 8C, and 1 atm of pressure). However, the pH value of body uid
may fall to 34 when there is inammation caused by surgery or
injury, due to inammatory cell secretions [31]. Combined with
uctuations in ionic strength in relation to high blood pressure, or
due to ion deposits, the human body presents an aggressive
environment for any implant. Furthermore, the internal partial
pressure of oxygen is about one quarter of atmospheric oxygen
pressure. While less reactive in terms of oxidation, lower oxygen
actually accelerates corrosion of metallic implants by slowing
down the formation of protective passive oxide lms on the metal
surfaces once an implant is broken or removed [31]. Ideally,
corrosion resistance should be such that the release of metal ions
from a metallic implant will be minimized in the harshest
conditions of the body, and remain at a satisfactorily low level
over a long service period (more than 30 years) under normal
physiological conditions.
2.3. Mechanical working conditions in the human body
To replace bone, which is satisfactorily strong and tough,
biomaterials must be able to match this mechanical performance.
The mechanical properties of general importance to biomaterials
development include Youngs modulus, ultimate tensile strength
(UTS) and toughness. A summary of these mechanical properties
for three dominant metallic biomaterials stainless steel, cobaltbased alloys and titanium-based alloys is given in Table 9. These
three metallic biomaterials remain popular primarily because of
their ability to bear signicant loads and undergo plastic
deformation prior to failure, as indicated by their respective UTS
and fracture toughness.
It must be mentioned that stainless steel, cobalt-based alloys
and titanium-based alloys have much higher Youngs modulus
Fig. 4. (a) Cytotoxicity of some pure metals. (b) The relationship between polarization resistance and biocompatibility of pure metals, cobaltchromium alloy and stainless
steels [27].
Table 9
Mechanical properties of metallic implant materials and cortical bone [33].
Materials
Youngs
modulus/GPa
Ultimate
tensile
strength/MPa
Fracture
toughness
p
(MPa m)
CoCrMo alloys
316L stainless steel
Ti alloys
Mg alloys
NiTi alloy
Cortical bone
240
200
105125
4045
3050
1030
9001540
5401000
900
100250
1355
130150
100
100
80
1540
3060
212
(more than 100 GPa) than that of bone which is only 1030 GPa
[33]. The higher modulus of elasticity of the implant may result in
its bearing nearly all the load, however bone that bears less
mechanical load can undergo biological responses such as atrophy,
particularly around the implant site; further revision surgery is
thus required. This is called the stress shielding effect. Hence, it is
desirable to have an implant with similar Youngs modulus to that
of bones.
The mechanical working conditions within the human body are
complex. Human beings normally walk several thousand steps a
day at a rate of 1 Hz. As such, skeletal bone implants such as
articial hip joints, knee joints, spinal xations, plates and wires
suffer from fatigue due to cyclic loading. In the case of articial hip
joints, the loading stress level is several times higher than that of
the patient body weight [31]. This is because when hip joint is
located out of perpendicular alignment, such as during a step, most
of the body weight pivots on only one leg at a time. Loading stress
on a single leg is estimated to be 50 MPa on average, if a
hypothetical load of ve times of the body weight is applied to the
cross-section of the stem of a total hip prosthesis [31]. Assuming
that a person walks 2 103 steps, the total number of steps over
20 years is estimated to be 2000 365 day 20 years 1 107
cycles (Table 10). This kind of cyclic stress also occurs in dental
implants during chewing motion, and non-osseous tissue implants
such as pacemaker electrodes in response to myocardial activity. In
any case, cyclic loading promotes material fatigue more efciently
than static xed loading.
Fatigue strength (fatigue limit or endurance limit) refers to the
maximal amplitude (or range) of cyclic stress that can be applied to
a material without causing fatigue failure. Fatigue strength
sensitively varies with the microstructure of materials, surface
quality of products, and service conditions (e.g. load vectors, cyclic
frequency, wearing, and corrosion environment). A material
subject to a cyclic loading can fracture far below its UTS and even
below the yield strength of the material. Fatigue fractures are
dangerous because they occur under normal service conditions
with no warning prior to rupture. Indeed, medical devices
manufactured from any material that are expected to survive
millions of cyclic deformations over their lifetime require scrutiny
of the fatigue and fracture resistance, with fatigue fracture being
the major cause of premature failure in biomedical implants.
Fatigue usually initiates at a location that acts as a stress
concentration. In the real world, no materials are perfect.
Table 10
Typical fatigue mechanical working conditions of some implants [31].
Implants
Loading strength
Loading
frequency
(Hz)
Joints
107
1
1
109
107
Pacemaker
Tooth llings
Fig. 5. (a) A total hip prosthesis by Depuy, and (b) terminology of components.
Fig. 6. Two congruent joints in human bodies. (a) hip http://www.hughblackley.co.nz/total-hip-joint-replacement.htm and (b) shoulder http://www.emedicinehealth.com/
shoulder_dislocation/article_em.htm.
10
Table 11
Ranking of articulating surfaces for joint prosthetics in terms of wear-resistance.
Ball and socket
Wearing resistance
Superior
Excellent
Excellent
Excellent
Good
Good
Poor
Fig. 7. Two articial incongruent joints (a) knee and (b) ankle.
11
Table 12
Four categories of stainless steels and typical medical applications [44].
Material type
Application grade
Examples
Martensitic
Bone curettes, chisels and gouges, dental burs, dental chisels, curettes, explorers,
root elevators and scalers, forceps, hemostats, retractors, orthodontic pliers, and scalpels.
Ferritic
Austenitic
Duplex
Table 13
Compositions (wt%) of 316L stainless steel (ASTM F138) and variants [44].
ASTM code/UNS No of stainless steels
Cr
Ni
Mo
Mn
Si
Cu
F138/S31673
F1314/S20910
F1586/S31675 (Orthinox)
F2229/S29108
17.0019.00
20.5023.50
19.5022.00
19.0023.00
13.0015.00
11.5013.50
9.0011.00
0.10
2.253.00
4.006.00
2.004.25
21.0024.00
2.00
2.003.00
2.003.00
0.501.50
0.75
0.75
0.75
0.75
0.50
0.50
0.25
0.25
0.10
0.200.40
0.250.50
>0.90
0.030
0.030
0.08
0.08
0.025
0.025
0.025
0.03
0.010
0.010
0.010
0.010
12
13
ability for retention of nickel [132]. Released metal ions due to the
corrosion of the implants can also migrate into distant organs, and
are more readily able to cross cell membranes. Systemic toxicity
may be caused by the accumulation, processing, and subsequent
reaction of the host to corrosion products [133135]. When highdose nickel salts were injected into mice, accumulation of nickel
was observed in the liver, kidney and spleen, causing local
deleterious effects [136]. Increased nickel concentrations have also
been found in tissues adjacent to stainless steel implant materials
(116 and 1200 mg/L) as well as in some distant organs [133,
137]. Other factors, such as infection and mechanical damage
due to wearing and friction may further encourage nickel
release, raising the concentration retained local to the implant
site [138140].
3.3. Biocompatibility of 316L stainless steel
The use of stainless steel in medical implants began in the 1930s
[141], when cytotoxicity evaluation standards were yet to be
established. Hence there are almost no in vitro or in vivo reports
focusing on the biocompatibility of stainless steels both from this
period. The reasonably good biocompatibility of this alloy was
suggested by the early clinical success of total hip replacements in
1960s and 1970s. Further evidence of biocompatibility of 316L
stainless steel has been reported in many studies since then, when
used as a control material [142144]. More detailed review will be
given in the context referring to NiTi alloys (Section 8). In general,
316L stainless steel shows relatively good biocompatibility, but to
a less satisfactory level than CrCrMo and titanium alloys, due to its
greater corrosion rates [44].
316L < CoCrMo < Ti6Al4V
Poor
!
Biocompatibility
Good
14
Table 14
Mechanical requirements for 316L (ASTM F138) and variants in bar or wire [44].
Steels
Conditions
UTS, min/MPa
F138
Annealed
Cold worked
Extra hard
490
860
1350
190
690
40
12
F1314
Annealed
Cold worked
690
1035
380
862
35
12
F1586
Annealed
Cold worked
Hard
740
1000
1100
430
700
1000
35
20
10
F2229
Annealed
Cold worked
Cold worked
Cold worked
Cold worked
931
1062
1262
1496
1731
586
786
952
1227
1551
52
37
25
19
12
10%
20%
30%
40%
Table 15
Fatigue properties of 316L stainless steels (and F1586/S31675) (run-out at 106 or 107 cycles) [160].
Alloys
Cast/Forged 316L
Cold-worked 316LVM
Cold-worked 316LVM
Cold-worked 316LVM
Annealed 316L
Annealed 316L
Annealed 216L
ISO5832-9
<550
200
300
550
<600
<340
<290
<400
<460
<500
Refs.
1
0.053
[159]
[161]
0.0
0.1
0.1
1
1
0.01
[162]
[163]
[163]
[164]
[164]
[158]
Fig. 8. (a) Effect of SBF on the SN relationship of cast 316L stainless steel [159]. (b) Effect of 0.9 wt% NaCl solution on fatigue properties of low nickel, high nitrogen stainless
steel [158].
15
Fig. 9. (a) Corrosion scale on a Charnley stainless steel stem, and (b) pitting and corrosion of a Muller stainless steel stem after implant removal [166].
16
Table 16
Medical applications of stainless steels [44].
Materials
Devices
Applications
Wires
Harrington spine
instrumentation
Mandibular wire mesh
prostheses
Sutures
Neurosurgical aneurysm
and microvascular clips
Self-expanding stent
Balloon-expandable stent
Hydrocephalus
drainage valve
Trachea tube
Electronic laryngeal
prosthesis system
Stainless steel
Stainless steel
Stainless steel
Stainless steel
Stainless steel
Stainless steel
Intrauterine pressure-sensor
case
Osmotic mini-pump
Stainless steel
Radiographic marker
Stainless steel
Stainless steel
Stainless steel
Steel and stainless steel
Buttery cannula
Cannula
Acupuncture needle
Limb prostheses, orthoses,
and adaptive devices
Wound closure, repair of cleft lip and palate, securing of wire mesh in cranioplasty,
mandibular and hernia repair and realignment, tendon and nerve repair
Replacement of nonfunctioning stapes: various types comprised of wire and piston
or wire and cup piston (synthetic uorine-containing resin/stainless steel piston,
platinum and stainless steel cup piston, and all stainless steel prostheses)
Temporary or permanent occlusion of intracranial blood vessels; tension clips of
various congurations, approximately 2 cm (0.8 in.) or less in length and
constructed of one piece or jaw, pivot, and spring components (similar and
dissimilar compositions)
Treatment of tracheobronchial stenosis, tracheomalacia, and air collapse following
tracheal reconstruction: 0.457 mm (0.018 in.)
Dilation and postdilation support of complicated vascular stenosis (experimental):
Control of intercranial pressure: one-way valve
Breathing tube following tracheotomy and laryngectomy: tube-within-a-tube
construction
Electromagnetic voicing source following total laryngectomy: implanted unit
comprised of subdermal transformer, rectier pack, and transducer encased in type
316 stainless steel, with spring steel diaphragm
Anodic, cathodic, and sensing electrodes and lead wires: intramuscular
stimulation, bone growth stimulation, cardiac pacemaker (cathode),
electromyography (EMG), electroencephalogram (EEG), and lead wires in a large
number of devices
Atrial electrocardiograms: swallowed sensing electrode of short metal tubing
segments forced over plastic tubing
Hermetic packaging of electronics and power source: welded capsule
Inguinal hernia repair, cranioplasty (with acrylic), orthopedic bone cement
restrictor;
Retention of large dental amalgam restorations: cemented, friction lock, and selfthreading pins, placed approximately 2 mm (0.08 in.) within dentin with
approximately 2 mm (0.08 in.) exposed
Restoration of endodontically treated teeth: post xed within root canal
preparation, with exposed core providing a crown foundation
Restoration for extensive loss of tooth structure in primary and young permanent
teeth: preformed shell
Correction of malocclusion by movement of teeth: components include bands,
brackets, archwires, and springs
External clamp xation for fusion of joints and open fractures of infected
nonunions: external frame supporting transxing pins;
Measurement of pressure on sound: metal diaphragm, mounted in tension
Measurement of respiratory ow: metal arms supporting wire strain gage
Contraception: stainless steel (Majzlin spring, M-316, M device), stainless steel and
silicone rubber (Comet, M-213, Ypsilon device), stainless steel and natural rubber
(K S Wing IUD), stainless steel and polyether urethane (Web device)
Protective shroud for transducer
Continuous delivery of biologically active agents: implanted unit comprising
elastomeric reservoir, osmotic agent, rate-controlling membrane, and stainless
steel ow moderator and lling tube
Facilitation of postoperative angiography of bypass graft: open circle conguration
of 25 gage suture wires
Intravenous infusion
Coronary perfusion: silicone rubber reinforced with an internal wire spiral
Acupuncture: 0.26 mm (0.01 in.) diameter 510 cm (24 in.) length needles
Substitution, correction, support, or aided function of movable parts of the body,
and technical aids not worn by the patient: components such as braces, struts,
joints, and bearings of many items
17
Fig. 11. (a) Stem fracture after 8.6 years. Endosteal bone lysis surrounds the proximal half of the stem. The stem has subsided 1.6 cm, partly within the cement, partly together
with the distal cement mantle. (b) Fractured Exeter stem after 3 years. Graft shows incorporation distal to the lesser trochanter and resorption proximal to it [172,173].
18
Fig. 12. The principal stress contours, in MPa, in a hip prosthesis. The maximal tensile stress in the stem is around 200 MPa, and approximately 350 MPa in the neck [154].
Table 17
CoCr alloys used in surgical implants [44,181].
ASTM standard
Nominal compositions
Cast/wrought status
Medical application
F75-98
F90-97
F562-95
F563-95
F799-99
F961-96
F1058-97
F1537-94
Co28Cr6Mo
Co20Cr15W10Ni
Co35Ni20Cr10Mo
CoNiCrMoWFe
Co28Cr6Mo
Co35Ni20Cr10Mo
CoCrNiMoFe
Co28Cr6Mo
Cast
Wrought
Wrought
Wrought
Forged
Forged
Wrought
Wrought
Permanent implant
Short-term implant
Permanent implant
Short-term implant
Permanent implant
Permanent implant
Permanent implant
Permanent implant
Table 18
The roles of alloying elements.
Elements
On corrosion resistance
On microstructure
On mechanical properties
Cr
Form Cr23C6
Mo
Ni
19
20
Table 19
Some physical properties of Fe, Co and Ni elements.
Elements
Density (g/cm3)
Structure
Tensile
Compressive
Fe
7.9
211
Co
8.8
Ni
8.9
Ti
4.5
170
82
1538
210
180
75
1493
FCC
200
180
76
1455
116
110
44
1668
Table 20
Mechanical properties of cast and wrought cobalt-based alloys [44].
Alloys
Youngs
modulus
(GPa)
UTS (MPa)
0.2% yield
strength
(MPa)
F75/Cast, annealed
F75/P/M HIP
F799/Forged
F90/Annealed
F90/44% cold worked
F562/Forged
F562/cold worked, aged
F563/annealed
F563/cold worked
F563/cold worked, aged
F1058 wire
210
250
210
210
210
230
230
230
230
230
230
650890
1280
14001590
9501220
1900
1210
1800
600
10001310
1590
18602280
450520
840
9001030
450650
1610
9601000
1500
280
8301170
1310
12401450
Elongation
(%)
15
28
8
50
1218
Smooth un-notched
fatigue strength/MPa
(106 cycles R = 1)
200310
725950
600900
NA
590
500
690790
ASTM F75 is a cast CoCrMo alloy, and has a long history in the
aerospace and biomedical implant industries. In addition to its
excellent corrosion resistance, the main attribute of this alloy is
wear resistance. Distribution of Cr-rich carbides M23C6 and the
work-hardening ability of this alloy greatly enhance wear
resistance. Total articial hip joints made from this alloy are even
more viable, due to its excellent tribological properties against
plastic sockets, i.e. in a metal-on-plastic joint. A further feature of
F75 is the extremely large grain size observed in the original
casting. A ner grain size in general results in superior mechanical
properties, hence wrought Co-alloy came into use [44].
ASTM F799 is a wrought version of F75 alloy, mechanically
processed by hot forging rough billets to make the nal shape. To
have a good ability to be forged, the carbon content of a wrought
alloy must be sufciently low. Although the low carbon content
compromises wear resistance of wrought alloys, they are superior
in fatigue strength imparted by the wrought microstructure. As
mentioned previously, the primary strengthening mechanism in
wrought cobalt alloys is the solid-state phase transformation of
part of the matrix from a FCC to a HCP crystal structure by cold
working. The presence of two distinct crystal structures poses a
barrier to the motion of dislocations and leads to pronounced
strengthening. The strength (fatigue strength, yield strength and
UTS) of F799 alloy is approximately twice those of as-cast F75
(Table 20). Modern Metal-on-Metal joint prostheses are almost
always made from the F799 alloy (Fig. 13).
ASTM F90 is a wrought CoCrWNi alloy. Tungsten and nickel
are added to improve machinability and fabrication characteristics
[223]. In the annealed state, the mechanical properties of F990 are
similar to those of cast F75, but when cold worked to 44%, the
properties can be improved to be more than double (Table 16). This
difference in mechanical properties between F90 in the annealed and
work-hardened conditions means that caution must be taken to
ensure uniform deformation of the component [224], because
variations in mechanical properties may result in unexpected failure.
ASTM F562 is a wrought CoNiCrMo alloy [225]. The
microstructure of worked F562 is the HCP solid-state phase formed
from the FCC matrix by cold working. Subsequent age hardening in
the 425650 8C range acts to further strengthen these two phases
through the precipitation of carbides, primarily Cr23C6 [225]. Cold
worked and aged F562 can exceed tensile strength levels in excess of
21
Fig. 14. Fatigue strength values (in air) of implant stainless steels and cobalt alloys
[148].
Fig. 13. Femoral bearing head and cups made from the F799 CoCrMo alloy. http://
www.zimmer.co.uk/z/ctl/op/global/action/1/id/9226/template/MP.
22
Fig. 15. SN curves of (a) cast and (b) forged CoCr alloys in the air and in physiological solutions [228].
Interstitial
element
Substitutional element
a stabilizers
b stabilizers
O, N, C, B
H
Primarily neutral
with light a or
b stabilization
effect
Table 23
ASTM/UN standards for titanium and titanium alloys used for medical implants.
Category
ASTM
UNs no.
Materials
a microstructure
F67
R50250
R50400
R50550
R50700
CP-Ti
CP-Ti
CP-Ti
CP-Ti
ab microstructure
F136
R56401
F1472
R56400
F1295
R56700
F2146
R56320
F1713
F1813
F2066
R58120
R58150
Table 22
Impurity limits [63] for commercial pure titanium (wt%).
Materials
ASTM
ASTM
ASTM
ASTM
grade
grade
grade
grade
1
2
3
4
Fe
0.03
0.03
0.05
0.05
0.08
0.08
0.08
0.08
0.015
0.015
0.015
0.015
0.20
0.30
0.30
0.50
0.18
0.25
0.35
0.40
23
b microstructure
grade
grade
grade
grade
1
2
3
4
Ti13Nb13Zr
Ti12Mo6Zr2Fe
Ti15Mo
24
Table 24
Basic mechanical properties of titanium and titanium alloys developed for
orthopedic implants [44].
Materials
Youngs
modulus
(GPa)
0.2% yield
strength
(MPa)
Ultimate
tensile
strength
(MPa)
Elongation
(%)
a microstructure
ASTM grade 1
ASTM grade 2
ASTM grade 3
ASTM grade 4
115
115
115
115
170
280
380
480
240
340
450
550
24
20
18
15
ab microstructure
Ti6Al4V
Ti6Al7Nb
Ti5Al2.5Fe
Ti3Al2.5V
110
105
110
100
860
795
820
585
930
860
900
690
1015
10
6
15
7984
7485
840910
10001060
9701040
10601100
1016
1822
78
7588
83
655
870970
950990
800
880980
9801000
22
1720
1618
81
6593
5566
730740
760930
800
850
9001030
830
10
80100
40100
4658
350600
400900
600650
7001000
6501000
1025
1726
515
200700
5001500
5001350
9001800
1040
1050
b microstructure
Ti13Nb13Zr
Ti12Mo6Zr2Fe
(TMZF)
Ti15Mo
Ti15Mo5Zr3Al
Ti15Mo2.8Nb
0.2Si0.26O (21SRx)
Ti16Nb10Hf
Ti(1080)Nb
Ti35.5Nb7.3Zr5.7Ta
(TNZT)
Ti(7080)Ta
TiTaNb/Nb/Sn
TiZrNbTa
20
Table 25
Smooth (unnotched) fatigue strength of orthopedic implant alloys [44].
Alloy
Test conditiona
a microstructure
CP-Ti (Grade 1)
CP-Ti (Grade 2)
CP-Ti (Grade 3 and 4)
ab microstructure
Ti6Al4V
Ti6Al7Nb
Ti5Al2.5Fe
Ti15Mo5Zr3Al
(aged a + b
microstructure)
b microstructure
Ti13Nb13Zr
Ti12Mo6Zr2Fe
(TMZF)
Ti15Mo3Nb0.3O
(21SRx)
TNZT
TNZT-0.4O
Fatigue
limit/yield
strength
88
215
430
0.5
0.8
0.6
500
330
610
500600
580
560640
0.6
0.4
0.7
0.7
0.8
0.5
500
525
0.6
0.5
490
0.5
265
450
0.5
0.5
Fatigue
limit at 107
cycles/MPa
300
200300
400500
0.5
0.50.6
0.50.6
ab microstructure
Ti6Al4V
Ti5Al2.5Fe
Ti15Mo5Zr3Al
(aged a+b
microstructure)
b microstructure
Ti13Nb13Zr
Smooth
fatigue
limit at 107
cycles/MPa
Notch fatigue
limit at 107
cycles/MPa
Kfa
KTi6Al4Vb
500
580
560640
290
300
190
0.6
0.5
0.3
...
...
1.0
500
0.7
0.4
0.8
1.0
1.3
1.4
0.5
1.0
Ti12Mo6Zr2Fe
(TMZF)
525
335
215
410
316LVM
550
300
725950
Nonsensitive
to notch
1.41.8
a
K f Notch fatigue limit=smooth fatigue limit (under the same test conditions), is a fatigued strength factor.
b
K Ti6Al4V Fatigue limit of alloy=fatigue limit of Ti F6Al 4V (under the
same test conditions), is a fatigue strength factor relative to Ti6Al4V.
25
Table 27
Comparison of a, near a, ab and b Ti alloys [56].
Ti-alloys
Advantages
Disadvantages
Medical applications
CP-Ti
a or near a
As above
As above
Not yet
microstructure
ab microstructure
1. Can be strengthened by
heat treatment
b microstructure
1. High hardenability
2. Good ductility and toughness,
excellent forgeability and good
cold rolling capability (formability)
at the solution-treated condition
3. Good fractural toughness
High density
Low creep strength
Low tensile ductility in the aged state
low resistance to wearing
26
27
Table 28
Strength of chemical bonds [275].
Bond type
Length (nm)
Covalent
0.15
90
Non-covalent
Ionic
Hydrogen
Van de Waals
0.25
0.30
0.35
80
4
0.1
In water
90
13
1
0.1
Fig. 16. (a) The capsule tissue (marked with arrows) formed at the interface between cobalt alloy implant and bone. (b) The infused interface between a Ti implant and host
bone.
28
Fig. 17. (a) Covalent bonding between implant and tissues; and (b) biological bonding.
Fig. 18. In biological bonding, collagen bers insert into the surface layer of the
hydroxyapatite implant 3 month post implantation, delineated by the arrows [274].
29
30
Fig. 21. (a) Philip Wiles metal-on-metal prosthesis made out of stainless steel. (b) Austin Moors prosthesis made out of CoCr alloys. (c) McKeeFarrar prosthesis. (c) Ring
prosthesis. (d) Chanleys prosthesis.
31
Table 29
Historical evolution of total joint replacement [180].
Year(s)
Inventor(s)
Joints
Materials
Clinical outcomes
1890
1893
1919
192539
Knee
Hip
Wrist
Elbow
Shoulder
Hip
Hip
1938
1948
Hip
Hip
1950
Philip Wiles/London, UK
Robert and Jean Judet brothers/Paris,
France
Austin Moore/South Carolina, USA
19501970
Kenneth McKee/Norwich, UK
Hip
19601970
Peter Ring/Redhill, UK
Hip
1962pres
John Charnley/UK
Hip
Metal-on-Metal
CoCr alloy (vitallium)
Metal-on-Metal stainless steels or
Co alloys
Metal-on-Metal stainless steel,
Co alloy)
Metal-on-UHMWPE (stainless steel,
Co alloy, or Ti-alloys)
Hip
32
Fig. 23. The structure and components of a modern total hip replacement.
Table 30
Biomaterials used in modern total joint replacements [219].
Products
Stem
Head
Line
Cup
Year(s)
Stainless steels
CoCr alloy (vitallium)
Stainless steels
CoCrMo alloys
Stainless steels
CoCrMo alloys
No line
No line
No line
Stainless steels
No cup
Stainless steels
Co alloys
Stainless steels
CoCrMo alloys
1938
1950s
1950s
Stainless steelsa
CoCrMo alloys
Ceramics (Al2O3 or ZrO2)
UHMWPE
Stainless steelsa
CoCrMo alloys
Ti alloys
1960s
CoCrMo alloys
No line
CoCrMo alloys
1960s
CoCrMo alloys
Ti alloys
No line
1980s
CoCrMo alloys
Ti alloys
No line
CoCrMo alloys
2000s
Stainless steelsa
CoCrMo alloys
Ti alloys
No line
1950s
Ceramic-on-Ceramic
Ceramic-on-Metal
a
Today, stainless steels are rarely used in the joint components of total hip replacements, though some previously implanted stainless steel prosthesis are still in service.
Stainless steel 316L/CoCr couplings should be avoided.
33
Table 31
Major orthopedic implant manufacturers and materials of some hip replacements.
Company
Products
Materials
CoCrMo alloy
CoCrMo alloy
CoCrMo alloy
Stryker Corp.
Accolade TMZF
Accolade C Femoral Component
TMZF alloy
Forged cobaltchrome alloy
Biomet (BMET)
Cobaltchrome alloy
Technology
Wright Medical
Perfecta RS Stem
Perfacta1 Plasma Spray Stems
Titanium alloy
Titanium alloy
Exactech
1990s [307] to around 10% in the late 2010s [305,306,308,309]. Despite the huge success, failure of the femoral stem and loosening
caused by wearing of acetabular components, remain major and
serious post-implantation complications of all total joint replacement [31,145]. The failure incidence is especially high after
20 years implantation, being 3040% [308]. Failure analysis has
consistently revealed that fretting corrosion fatigue is the major
cause of stem fracture, with wearing between bearing surfaces
responsible for aseptic loosening [31,35,145]. As discussed in
Section 4.4, the corrosion fatigue strength of wrought CoCrMo
alloys in simulated body uid is around 200 MPa after 10-years
service, a similar level to the working stress of 200 MPa for a stem
of hip prosthesis under normal working conditions. Hence, fatigue
or corrosion fatigue is likely to cause the fracture of the stem.
It is also important to bear in mind that the difference between
estimates of material parameters under in vitro versus in vivo
conditions is such that the corrosion fatigue and fretting corrosion
fatigue strengths of metallic material implants may be overestimated by in vitro testing. The in vivo working conditions are
also mechanically and biologically complicated. Normal physiological loading provokes a combination of various deformation
Fig. 24. Proportion of total hip arthroplasty by bearing surface across time [306].
34
Fig. 27. Cumulative improvements in survival rate reported in (a) 1996 [307] and (b) 2007 [308].
35
Table 32
Advantages and disadvantages of stainless steels, Co-alloys and titanium alloys.
Alloys
Advantages
Disadvantages
Typical application
Fe-based (316L)
Instruments
Temporary implants
Co-based
Permanent implants
Ti-based
Light
Greatest corrosion resistance
Excellent biocompatibility
Relatively low Youngs modulus
Fig. 28. Fatigue strength at 107 cycles of biomedical stainless steel, cobalt alloys, titanium and its alloys, and bone. Data without designation of rotating bending are those
obtained from uniaxial fatigue tests in air [228].
36
Table 33
Three generations of biomaterials.
Generation
Bioactivity
Clinical goals
Examples
First
Biologically inert
No harm to tissues
Co-alloys
Al2O3
Polyurethane
Second
Surface erosion
Tissue-bonding
Titanium alloys
Hydroxylapatite
Calcium phosphate
Surface bioactive glasses
Third
Biodegradation
Tissue regeneration
Magnesium alloys
Degradable Bioglass1
Degradable polymers (PLA, PGA, etc.)
(1)
(2)
(3)
The hydrogen evolution in ligree implants, such as cardiovascular stents, seems to be of minor importance [5]. Preclinical and
clinical studies indicate good biocompatibility, with minimal
inammatory changes and complete absorption within two
months [12,313316]. In bone biosynthesis applications, where
vascularization and nutrient transport is minimal, hydrogen
evolution however remains problematic [5]. As a result of the
increased Mg mass and poor transport mechanisms, gas pockets
occur around these implants. In animal studies, subcutaneous gas
bubbles have had to be removed by means of puncture procedures
[11,317]. The corrosion of magnesium is strongly inuenced by
alloying elements in solid solution [5]. Experimentation has shown
that the addition of Zn has the ability to signicantly decrease the
amount of hydrogen gas evolved when measured by electrical
corrosion testing [4].
There have been a number of alloying elements used in
magnesium based materials in an attempt to control their
corrosion properties and feasibility as implants. Elements like
Mn, Cu, Al, Ca, Zr, Gd, and Zn have all been explored (Table 35)
[39]. Progress in the development of new compositions and highpurity alloys has produced improved corrosion resistance and thus
a decrease in hydrogen evolution rates [318]. However, the
solubility of alloying elements in crystalline Mg is limited, and thus
corrosion rates can only be altered within a limited range.
Hydrogen evolution will thus remain a problem during the
degradation of crystalline Mg alloys.
Table 34
Composition (wt%) for magnesium alloy.
Type
Group (example)
Al
Mn
Si
Zn
Ag
Cu
Zr
Nd
Ni
Cast
AM series (AM20)
AS series (AS21)
AZ series (AZ61)
EQ series (EQ21)
EZ series (EZ33)
QE series
WE series (WE43)
ZC series (ZC63)
ZE series (ZE41)
2
2
6
0.5
0.4
0.2
0.5
00.15
0.7
23.1
6
3.55
1.52
22.5
0.075
00.1
2.7
00.1
0.7
0.51
0.6
0.5
0.41
2.25
3
2
3.25
1.3
00.01
00.01
Wrought
AZ series (AZ31)
EA series (EA55RS)
WE series (WE54)
Z series (Z6)
ZC series (ZC71)
ZK series (ZK60A-F)
ZM series (ZM21)
ZW series (ZW3)
3
5
0.3
0.75
0.5
0.45
0.6
4.9
3.15
1
5
6
6.5
6
2
3.25
1.25
5.1
37
Table 35
The in vitro and in vivo corrosion rates of magnesium alloys [321].
Alloys
Pure Mg (99.85%)
AZ31
AZ91
WE43
ZE41
LAE442
AZ91Ca
AZ61Ca
Cast MgMnZn
Extruded MgMnZn
Extruded MgZnY
Cast Mg1Ca
Extruded Mg1Ca
0.9 wt%
NaCl
0.9 wt%
NaCl
34
10
22.56
27
30
Hanks
solution
SBF
15.98
31.60
80.06
30.60
16.03
m-SBF
65.70
Hanks
solution
SBF
0.011
0.0065
0.0028
0.038
In vivo corrosion
rate (mg/cm2/yr)
m-SBF
1.17
1.38
1.56
0.085
0.0626
0.39
17.80
36.50
1.451.60
0.0030.010
79.17
1.884.47
546.09
75.65
0.92
0.05
0.0150.04
0.136
0.040
1.28
7.5.1. Magnesium
Magnesium is needed for more than 300 biochemical reactions
in the body. At the biochemical level, magnesium is involved in
energy metabolism and protein synthesis, maintains normal
muscle and nerve function, supports a healthy immune system
and keeps bones strong. Magnesium also helps regulate blood
sugar levels and promotes normal blood pressure, playing
important roles in preventing and managing disorders such as
hypertension, cardiovascular disease and diabetes [332,333]. Dietary magnesium is absorbed in the small intestines and is excreted
through the kidneys [332,333]. The kidneys are efcient at
excreting excess magnesium and it is unlikely that the mineral
will accumulate to toxic levels, although there is a risk of renal
dysfunction with an overdose of magnesium, due to precipitation
of magnesium salts. A high intake of magnesium can compete with
calcium, and lead to impairment of its absorption [334]. Symptoms
of magnesium overload include diarrhea, difculty breathing and
depression of the central nervous system, causing muscle
weakness, lethargy, sleepiness or even hyperexcitability [335].
7.5.2. Calcium
Calcium is the most abundant mineral and mainly stored in
bones and teeth. Other diverse biological roles in the human body
including blood clotting and co-activation and stabilization of
enzymes [336338]. Compared with other metals, the calcium ion
and its compounds have very low toxicity. This is not surprising
38
Table 36
The pathology and toxicology of Mg and its alloying elements [321,356,357].
Elements
Blood serum
level
Biological role
Toxicology
Daily allowance
Mg
0.9 mmol/L
0.7 g
Ca
1.3 mmol/L
0.8 g
Cu
1.11.5 mg/ml
23 mg
Zn
46 mmol/L
Mn
1 mmol/L
Si
Li
24 ng/g
Al
2.14.8 mg
Zr
Total, <250 mg
Rare earth
elements
<47 mg
15 mg
4 mg
0.20.6 mg
Total amount in
human <300 mg
3.5 mg
Youngs
modulus
(GPa)
UTS
(MPa)
0.2% yield
strength
(MPa)
Elongation
(%)
Mg-cast
AZ91D-die cast
AZ31-extruded
LAE442
AE43-extruded T5
AM60B-die-cast
MgZnMn extruded
Mg1Ca-extruded
41
45
45
87
230
235
247
280
220
180
240
21
150
125
148
195
13
3
7
18
10
68
22
11
44
45
246
135
39
Fig. 29. Tensile strength, 0.2% elastic limit, elongation at rupture, and elongation at tensile strength of several MgCa alloys [361,365].
40
Fig. 30. The use of NiTi in vascular stents is based in its superelasticity and shape memory effect.
Table 38
The corrosion behaviors of NiTi alloys [102].
Testing conditions
Major results
Refs.
NiTi has better corrosion resistance than CoCrMo or 316L stainless steel
NiTi is more sensitive to corrosion than titanium. Pitting of the NiTi surface was observed
NiTi has a better resistance to the chemical breakdown of passivity, compared to 316L
When stainless steel (316L) was coupled with NiTi, 316L was found to suffer from crevice corrosion
NiTi wires are no more subject to corrosion than stainless steel
The release rates of nickel from stainless steel and nickeltitanium arch wires were not signicantly
different
The Ni ion release was three times higher for NiTi than for austenitic stainless steels
The characteristics of the passive lm formed on NiTi are not so good as those on Ti6Al4V, but are
comparable or inferior to those on austenitic stainless steels
Annealed NiTi to be more corrosion-resistant than cold-worked material. Thus, the heat treatment
and mechanical working had a signicant inuence on corrosion behavior. The same study also
indicated that straining of NiTi led to signicant improvements in corrosion resistance. This may be
due to the development of a single martensite variant during deformation
No generalized or localized corrosion on NiTi. Neutron activation analysis of distant organs in the
same study showed no accumulation of trace metals from NiTi
[372]
[373]
[374]
[375]
[376]
[377]
[381]
Evaluated in physiological
simulating uids
Ringers solution
In vivo:
NiTi plates, 17 months after
implantation in dogs
Implanted 44 NiTi intraluminal
stents in the iliac arteries
of 22 sheep
[378]
[379]
[380]
41
Table 39
In vitro studies on biocompatibility of NiTi alloys.
Cells
Control materials
Major results
Refs.
[382]
Human broblasts
No
L-929 broblasts
No
Rat splenocytes
No
Fibroblasts
316L stainless steel and CoCr alloy did not differ in cell growth from the
negative control cultures, but NiTi and titanium signicantly reduced cell
growth. The morphological changes of cells with NiTi and titanium were
also more pronounced
Nickel induces a signicant inhibition of mitosis in human broblasts,
whereas no signicant effects of this kind were found for titanium or
NiTi. NiTi was considered biocompatible and comparable to titanium
All metals induced a mild biological reaction. The cytotoxicity of NiTi was
found to be approximately equal to that of CoCrMo, both being more
than that of pure titanium, Ti6A14V or 316L stainless steel
Human plasma bronectin (pFN), an adhesive protein, can be covalently
immobilized onto NiTi substrate and signicantly improved human
gingival broblast spreading, suggesting that this chemical modication
enables the controlling of metal/cell interactions
Cells exposed to NiTi are critically affected by the surface preparation.
The hydrogen peroxide surface treatment of NiTi caused a toxic effect
comparable to that of pure nickel. However, the situation changed
tremendously when NiTi was treated by autoclaving in water or steam.
The reaction with these NiTi specimens was clearly non-toxic
The NiTi alloy showed no cytotoxic, allergic or genotoxic activity. The
ndings were similar to those on 316L stainless steel. Conclusion: The
NiTi alloy can be regarded as a biologically safe implant material
These three alloys induced similar DNA strand breaks of interphase
chromatin, but stainless steel induction on metaphase chromatin was
more intense than with NiTi or pure titanium. Conclusion: NiTi
genocompatibility is promising in view of its biocompatibility approval
NiTi, stainless steel and b-titanium alloy wires had no effect on the rate
of cell proliferation. The most severe growth inhibition was induced by
the CoCrNi alloy
No cytotoxicity was detected in the direct-contact evolution testing
The results indicate a good biocompatibility for a nickel content up to
about 50%
In the NiTi and Ti groups, the number of dead cells was signicantly
lower than in Ni group. Conclusion: NiTi is well tolerated by the
osteoblastic type ROS-17 cells
1. The plasma-treated surfaces are cytologically compatible allowing the
attachment and proliferation of osteoblasts
2. The sample with surface titanium nitride exhibits the largest degree of
cell proliferation whereas stainless steel fares the worst
Oxidized NiTi surfaces enhance differentiation of osteoblast-like cells
The adhesion, spreading, and proliferation of osteoblasts on the
implanted NiTi surface are assessed by cell culture tests. Our results
indicate that the nano-scale surface morphology that is altered by the
implantation frequencies impacts the surface free energy and wettability
of the NiTi surfaces, and in turn affects the osteoblast adhesion behavior
[397]
Osteoblasts
Stainless steel
MG63 cells
Osteoblasts
No
No
[387]
[388]
[389,390]
[391]
[392]
[393]
[394]
[395]
[396]
[383385]
[386]
[398]
42
Table 40
In vivo studies on biocompatibility of NiTi alloys with animals.
Animal model/maximal duration
of implantation
Control materials
Major results
Refs.
[370]
N.A./3 months
No
Hydroxyapatite
No
Paravertebral implantation in
4 rabbits/4 weeks
No
6 rabbits/3 weeks
No
No
No
[380]
[399]
[400]
[401]
[402]
[371]
[403]
[404]
[405]
[406]
[407]
[408]
43
Table 41
In vivo trials of NiTi implants in human.
Applications/period
Number of patients/implant
duration
Major outcomes
Refs.
77 patients, 93 fractures
using 124 clamps/6 weeks
[413]
Maxillo-facial fractures
51 patients/9 months
50 patients/7 weeks
84 patients
36 patients
64 patients
[414,415]
[416]
[417]
[418]
[419]
[420]
44
Table 42
Biocompatibility of bare NiTi wires as stents (lters) and closures (without coating).
Number of patients/implant duration
Intravascular stents
66 endovascular NiTi prostheses implanted
in 36 dogs/14 months
12 intravascular NiTi stents implanted in
the iliac and femoral arteries of 6 normal
dogs/2 years
44 NiTi intraluminal stents implanted in
the iliac arteries of 22 sheep/6 months
14 vascular stents in 14 dogs/9 months
Urethral stents
18 Urethral NiTi stents implanted in 18 dogs/1
week and 1, 3, 6, 12 and 18 months
Urethral stents implanted in 39 patients
(human)/26 months
Closures
Atrial septal defect closure device in 20 adult
dogs/8 weeks
Major outcomes
Refs.
[421]
Conclusion: Despite the excellent biocompatibility of the material with no evidence of foreign
body reactions or corrosion, there were no complete incorporations of the stent by
epithelialization. Clinical application therefore appears to be problematic
39 patients with benign prostatic hyperplasia had NiTi urethral stents implanted with a
clinical success rate of 89%. Follow-up for 26 months showed no incrustation or migration of
the spiral
Percutaneous transcatheter closures were attempted using the new device. The closures
were successful in 19 studies and unsuccessful in one. At 8 weeks in 3 dogs showed the
devices to be covered by smooth endocardium enmeshed in mature collagen tissue, with
minimal mononuclear cell inltration
Conclusion: This new device permits effective and safe atrial septal defect closure in a canine
model
No problems related to early migration and expulsion were observed, and no anastomotic
leakage and bleeding occurred
Conclusions: Intestinal anastomosis with the NiTi was safe and feasible without anastomotic
leakage and reoperation compared with the stapling technique
[422]
[381,423]
[424]
[426,427]
[428]
[429432]
[433]
[434]
[435]
[436,437]
[438]
[439]
45
Table 43
Biocompatibility of coated versus bare NiTi stents.
Number of patients/implant duration
Intravascular stents
14 patients
Major outcomes
Refs.
[440]
[441]
[442]
[443]
PTFE, polytetrauoroethylene.
8.6.1.3. Urological applications. The use of NiTi stents has also been
expanded to treat prostatic obstruction by Lopatkin and coworkers [458,459]. For patients with a high operative risk the
insertion of a permanent metal stent system offers a useful
alternative to treat subvesical obstruction caused by prostatic
carcinoma [460462], and benign prostatic hyperplasia [461,
463]. The use of urethral stents was found to considerably
decrease the number of repeated dilatations and urethrotomies in
recurrent urethral strictures [464,465]. Despite the good biocompatibility of NiTi in a long-term canine study, there were no
complete incorporations of the stent by epithelialization, and so
there is a concern that clinical application might be problematic
[435].
46
Fig. 31. Various Nitinol (NiTi) stents/lters. (a) Simon Nitinol Filter (SNF), FDA approved in 1990. (b) G2 (Bard Peripheral Vascular), FDA approved for permanent use in
2005 and for retrievable use in 2008. (c) OptEase, FDA approved for permanent use in 2002 and retrievable use in 2004. (d) SafeFlo, FDA approved for permanent use only in
2009. (e) Option. (f) Vena Tech LP, FDA approved in 2001. (g) Biliary stent, FDA approved in 1999. http://www.whichmedicaldevice.com/editorial/article/104/a-brief-historyof-inferior-vena-cava-lters-and-analysis-of-current-devices.
Fig. 32. Radiograph of the inferior vena cava implanted with Vena Tech LP (yellow
arrow) and OptEase (blue arrow). http://www.ceessentials.net/article12.html. (For
interpretation of the references to color in this gure legend, the reader is referred
to the web version of the article.)
47
Table 44
Orthopedic and orthodontic applications of NiTi.
Animal models
Correction rods of scoliosis
The functional principle of the NiTi memory
wire was demonstrated in an experiment
carried out on a plastic model
26 patients
1 scoliosis monkey/4 weeks
Major outcomes
Refs.
NiTi wire prestretched by 7% is led through eyelets on the convex side and xed at the ends. On
being heated, the wire shortens, righting the model so that it assumes a straight shape
[482]
[473]
[371]
No procedural complication or adverse reaction to the clip was noted. There was no movement at
the operated level in dynamic lateral view X-ray of cervical spine at the 1st postoperative day as
well as on follow-up. Graft extrusion was seen in one patient on the 2nd day after surgery and was
re-operated. Bony fusion occurred in all patients after 912 months of surgery. There was no
incidence of breakage or dislodgement of the clip from the site where it was inserted
Conclusion: NiTi clips are a simple alternative for cervical spine stabilization after discoidectomy.
Their insertion is simple, minimally invasive, does not require any special set of instruments and
they are much more economical than other established methods of treatment. These clips are
accepted well by human tissue and do not interfere with MRI
rods for scoliosis and xation staples for long bone (Table 44). Early
trials indicated that the scoliosis-correction system based on NiTi
shape memory had quite complicated biomechanical problems
related to compression and distraction control. NiTi may not
provide any improvements compared to the traditional implant
systems [371,472]. However, a follow-up study from China in 1986
[473] reported satisfactory performance of NiTi rods in 26 scoliosis
patients. Successful applications of NiTi in correction of scoliosis in
38 patients were reported in another more recent follow up report
in 2011 [474].
[472]
[483]
[474]
[425,448]
Fig. 34. Non-screw anchors Mitek G2, Mitek Rotator Cuff Anchor, and Linvatec Ultrax RC from left to right, all containing NiTi [478].
48
Table 45
Mechanical properties of NiTi alloys in comparison with the 316L stainless steel and cortical bone [44,444].
Alloys
Youngs
modulus (GPa)
0.2 yield
stress (MPa)
Maximal elastic
strain (%)
UTS
Elongation
at rupture
Fracture toughness
(MPa m1/2)
316L
NiTi (austenite)
NiTi (martensite)
Cortical bone
200
5080
3040
730
200700
200700
70140
NA
0.20
10
10
NA
500850
9001355
NA
50150
1040
14.3
NA
NA
100
3060
NA
212
which prevent the anchor from pulling out of the bone after
insertion and securing of tendons or ligaments back onto the bone
[479,480]. Another potential application of NiTi is a hook used to
restore the dislocated acromio-clavicular joint of the shoulder
[481].
Most published studies in the orthopedic eld have not satised
the basic quality criteria of scientic study. The data are not
convincing enough to say that a certain NiTi implant can be used
without harm. To be considered fully successful, it must be proved
to be better than the existing competitors. At present, there are no
comparative clinical studies and the sample groups have generally
been small. Randomized prospective studies are needed to apply
new NiTi implant devices for long-term clinical use in humans
[102].
8.7. Mechanical properties of NiTi alloy [43]
8.7.1. General mechanical properties
The mechanical properties of NiTi alloy are unique. Youngs
modulus of NiTi alloy is in the range of 3050 GPa [444], the closest
to that of cortical bone of human, even closer than b Ti alloys and
MgZn alloys (Table 9). The relatively low level of Youngs modulus
in NiTi alloys does not affect their yield strength and UTS, which are
comparable with those of stainless steels (Table 45). The most
attractive mechanical property of NiTi is its large elastic strain of
10%, which is one order higher than any traditional alloys.
8.7.2. Fatigue properties of NiTi alloys
The mechanical properties, especially fatigue properties, of NiTi
alloy sensitively depend on the deformation temperatures,
whether in austenite or martensite phase. The fatigue strength
of austenitic NiTi alloys is in general higher than that of martensitic
alloys (Fig. 35a), and the fatigue strength of austenitic NiTi alloys is
higher at elevated temperatures (Fig. 35b). At both room and body
Fig. 35. SN curves of NiTi alloys. (a) Fully reversed (R = 1) stress based fatigue curves to 107 cycles. The fatigue limit for the austenite (Af = 10 8C) is signicantly higher
than the martensite (Af = 110 8C) phase [484]. (b) The tensiontension stress based fatigue curves up to 106 cycles, with an Af of 27 8C. The 106 cycles fatigue limit at 30 8C is
lower than that obtained at 60 or 160 8C [485]. Note: Af is the nish temperature of phase transformation in the alloy.
49
Fig. 36. (a) Plastic strain amplitude per cycle for four Nitinol compositions tested under constant strain tensioncompression conditions at room temperature. In general,
these data show that fatigue life tends to increase with increasing Af temperature for annealed Nitinol. (b) Effect of cyclic strain amplitude on the rotary bending fatigue life for
NiTi wires at three test temperatures for an Af of 40 8C. The low cycle fatigue behavior is greatly affected by the test temperature with an order of magnitude improvement in
fatigue at 20 8C compared with that at 80 8C. However, with this limited dataset, there does not appear to be a difference at the high cycle regime. (c) The thermal martensite
data have greater low cycle and high cycle lives compared with the three sets of data for superelastic conditions [43].
Table 46
Fatigue strength of NiTi alloys in comparison with stainless steel, cobalt and titanium based alloys.
Alloys
NiTi alloys
Forged 316L
Forged CoCrMo alloys
Ti alloys
100400
300350
600900
500600
NA
100200 (stress control)
200300 (stress control)
400600 (stress control)
(strain control)
(unnotched stress control)
(unnotched stress control)
(unnotched stress control)
Refs.
[228]
[228]
[228]
50
Table 47
Compositions, maximum weight percent allowed for unalloyed tantalum in accordance with ASTM F560.
Processing condition
a
Annealed
Cold-workedb
a
b
Hardness (HV)
UTS (MPa)
Elongation (%)
80110
120300
186191 (2728)
186191 (2728)
140 20
345 50
205 30
480 70
2030
125
Table 48
Mechanical properties for unalloyed tantalum (ASTM F560).
Processing condition
Hardness (HV)
UTS (MPa)
Elongation (%)
Annealed
Cold-worked
80110
120300
186191 (2728)
186191 (2728)
140 20
345 50
205 30
480 70
2030
125
Fig. 37. OXINIUM oxidized zirconium has been introduced to reduce the wear rate
over the CoCrMo alloy total knee implants. http://global.smith-nephew.com/us/
patients/OXINIUM.htm.
11. Silver
11.1. Biocompatibility of silver
Silver has no known biological roles, and possible health effects
of silver are a disputed subject [521523]. Although silver itself is
non-toxic, most silver salts are, and some may be carcinogenic
[524]. Silver ions can bind to sulphur groups in inter-molecular
bonds in some biomolecules [525].
11.2. Medical application of Ag
Silver ions and silver compounds show a toxic effect on some
bacteria, viruses, algae and fungi, but without causing the high
toxicity to humans. Its germicidal effects can kill many microbial
organisms [526,527]. Because of this, silver salts and the metal
itself have played an important part in the development of
medicine. Interest in the use of silver is being rediscovered in a
wide variety of biomedical applications, where it can prevent the
growth of microorganisms responsible for disease [528,529]. The
antimicrobial properties of silver are used in the form of silver salts
and nano-scale complexes that break down to release silver ions
(Ag+).
Metallic silver is also used in a number of surgical applications,
both for structural devices (e.g. cranial support plates, suture wire,
aneurysm clips, and tracheostomy tubes) and for prostheses (e.g.
silicon-silver penile implants) [530,531].
12. Metals used as medical electrodes
An important and challenging medical use of implanted
electrodes is in prosthetic devices for neural [532534] or muscle
stimulation. These devices employ metal electrodes to transmit the
current required for electrical stimulation of appropriate areas of
the nervous system. Neural prostheses for direct control of
peripheral organs include the cardiac pacemaker, the phrenic
stimulator for respiratory control and spinal cord stimulators for
bladder control [535539]. More complex neural control devices
include auditory prostheses for deafness, experimental visual
prostheses for blindness and neuromuscular prostheses for
muscular entrainment to restore limb function in paralyzed
individuals.
The most frequently considered metals for electrical stimulation are the so-called noble or precious metals: platinum, iridium,
rhodium, gold, and palladium. This is because of their resistance to
chemical and electrochemical corrosion. However, all of these
metals show corrosion effects during both in vitro and in vivo
electrical stimulation. Corrosion effects include weight loss,
formation of unstable surface lms that tend to spall from the
surface, and dissolution of metal [540]. Of the noble metals,
platinum and platinum-iridium alloys containing 1030% Ir are the
most widely used for electrical stimulation. Metal oxides such as
iridium oxide have also shown promise. Some non-noble metals
are candidates for electrode applications requiring high mechanical strength and fatigue resistance such as demanded by
intramuscular electrodes. These include vacuum melted type
316L stainless steel, Cobalt alloys Elgiloy and MP35N, pure forms of
zirconium, tungsten, tantalum, and titanium, and tungsten
bronzes made by powder metallurgy processing [540].
13. Metallic materials used in orthodontic implants
Metallic biomaterials have been applied in dentistry and dental
surgery (Table 49) for dental restoration, endodontic implantations
and orthodontics [541543]. Cobalt-based alloys and Ti6Al4V
are used to replace tooth roots, stainless steels and NiTi alloys are
51
Table 49
Metallic materials used in dentistry [543].
Alloys
Compositions (wt%)
CuZn alloys
(no longer used)
Nickel silver
(no longer used)
HgAgSnCu amalgam
Au-alloys
6588Cu, 1235Zn
Stainless steels
CoCrNiMo alloys
CP-Ti
(a + b)-Ti alloys
b-Ti alloys
NiTi-martensitic
NiTi-austenitic
TiNb
TiTaNb/Zr/Sn
TiZr
NiTa
Table 50
Mechanical properties of dental metallic implant materials [543].
Alloys
Youngs
modulus
(MPa)
Yield
strength
(MPa)
UTS (MPa)
CuZn alloys
Nickel silver
HgAgSnCu
100120
120
Varying
with time
85110
180220
180230
100110
100120
2844
80110
6570
6593
65110
4560
173220
70460
140540
Varying
with time
170570
7902450
9602140
1701000
7401130
701240
180690
5201380
760930
300600
NA
65500
260900
390640
150160
(compressive)
3201120
9302860
12102540
2401100
8601220
9001930
8001670
6901500
9001030
500700
6501000
300850
Au-alloys
Stainless steel
CoCrNiMo alloys
CP-Ti
(a + b)-Ti
NiTi-martensite
NiTi-austenite
b-Ti
TiNb
TiTa
TiZr
NiTa
52
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