**1. Introduction**

Starting with the twentieth century, a wide range of alloys have been used in medical applications as surgically implanted medical devices or denture materials, aimed at providing improved physical and chemical properties, such as strength, durability, and corrosion resistance [1, 2].

The classes of alloys used in medical devices and denture materials include stainless steels, cobalt-chromium, and titanium (alloyed and unalloyed) [3].

Orthopedic implants are subjected to heavy and cyclic load bearing, and they work in a bioactive environment. Most parts of hip joint implants are made of metallic materials. Titanium alloys are considered to be the most advanced materials in this type of application. However, Co-Cr-Mo alloys and austenitic stainless steels

as biosteels paired with appropriate metallic alloys, ceramics, and polymers are also being used for hip implant components [4].

The alloys currently accepted for orthopedic implant applications are:


The biocompatibility of any material in contact with a living tissue is part of the general context of chemical toxicity effects on the human body [5–7]. A biocompatible material may be defined as inert, nontoxic, non-mutagenic, non-recognizing, nonirritating, and non-allergenic [8–9].

Since the early twenty-first century, Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) [7, 10] regulates Europe's approach regarding chemical toxicology to humans, aiming to list the substances present in Europe (manufactured or imported in volumes exceeding one ton) and to control the highrisk substances while reconciling public health and environmental protection.

According to the European Chemicals Agency (ECHA) [11], the list of preregistered substances contains around 143,000 chemicals. Substances that may have serious effects on human health and the environment can be identified as substances of very high concern (SVHCs):


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*Multicomponent Alloys for Biomedical Applications DOI: http://dx.doi.org/10.5772/intechopen.88250*

derivatives, and Be and its derivatives.

with or without contact lubricant.

by its electrode potential.

chemical forms [17].

resulting oxides [20].

reveals mutagenic properties—Sn2+, Cu2+, and Fe2+.

without degrading within an acceptable time limit [17].

effect: allergic, irritating, mutagenic, and toxic [7].

which are made of stainless steel and Co-Cr alloys [18].

fied into three classes:

Pd, In, and G [8, 9, 14].

Among the SVHCs incriminated by ECHA, about 4000 substances which can cause a contact allergy are listed. It is estimated that 15–20% of Europe's population are sensitized to allergens. Allergic reactions are a significant and growing health

According to the International Agency for Research on Cancer, metals are classi-

Class 1: The agent is carcinogenic to humans—Ni derivatives, Cr6+, Cd and its

Metals with none or limited references as mutagens are Cu1+, Sn4+, Au, Pt, Ag,

Corrosion is an electrochemical reaction characteristic to all metals in contact with biological systems, and its consequence is the formation of metal ions which may trigger hypersensitivity reactions and affect the immune response system [15]. It characterizes the chemical reactivity of metals and alloys, which results in a visible alteration of the material and affects the function of a metallic component or of the entire ensemble [16]. Crevice corrosion is the localized corrosion of a metal surface at, or immediately adjacent to, an area that is shielded from full exposure to the environment because of the close proximity between the metal and the surface of another material (ASTM G15-97). Tribocorrosion refers to all the mechanical and chemical interactions that cause the degradation of solids in relative displacement

A major characteristic that concerns any metallic material used for medical applications is good resistance to corrosion, and this is the most relevant property when it comes to its biologic safety [8]. The tendency of a metal to corrode is given

Conceived for a biological environment, alloys for medical use should essentially be integrated without developing adverse effects, maintaining their function

The potential systemic and local toxicity, allergy, and carcinogenicity result from releasing elements during the corrosion process. Elements such as Ni and Co are known for their high allergic potential, and prudence dictates that alloys containing these elements should be avoided as much as possible. Several elements are known mutagens, and a few, such as Be and Cd, are known carcinogens in different

The potential negative effects on the tissues or on the body at cellular level are precisely induced by the presence of certain components released as degradation products, especially metal cations in solution, due to surface corrosion [9]. The degradation of metallic devices in a biological environment is accompanied by the release of cations such as Cr, Co, Ni, and Ti. Therefore, we deal with a cumulative

Metal ions and debris have been shown to be released from orthopedic implants

Cr, Mo, Si, Fe, and Mn are the ions released from stainless steel implants, while Ti, Al, V, and Nb are released from titanium alloy implants [19]. The in situ degradation of an implant decreases its structural integrity and also releases products which may trigger an adverse biological reaction [15]. Biological risks associated with the released metal ions have been identified to include those from wear debris, colloidal organometallic complexes, free metal ions, and inorganic metal salts or

Class 2: The agent is possibly carcinogenic to humans—metallic Ni and Co. Class 3: The agent is not classifiable as to its carcinogenicity to humans but

problem affecting large parts of the European population [7, 13].

*Engineering Steels and High Entropy-Alloys*

Steel Forgings

Shape Memory

• Tantalum: Unalloyed Tantalum

nonirritating, and non-allergenic [8–9].

stances of very high concern (SVHCs):

reproduction.

being used for hip implant components [4].

Cobalt -28Chromium-6Molybdenum Powder

as biosteels paired with appropriate metallic alloys, ceramics, and polymers are also

Strengthened 21Chromium-10Nickel-3Manganese-2.5Molybdenum; Nitrogen Strengthened 23Manganese-21Chromium-1Molybdenum Low-Nickel; Stainless

The alloys currently accepted for orthopedic implant applications are:

• Stainless steels: 18Chromium-14Nickel-2.5Molybdenum; Nitrogen

• Cobalt chromium alloys: Cobalt-28 Chromium-6 Molybdenum; Cobalt-20Chromium-15Tungsten-10Nickel; Cobalt-28Chromium-6Molybdenum;

• Cobalt chromium nickel alloys: 40Cobalt-15Nickel-20Chromium-7

• Titanium & titanium alloys: Unalloyed Titanium; Titanium Alloy in the

• Zirconium: Zirconium-2.5Niobium Stabilized Zirconium (Mg-PSZ)

Cobalt-35Nickel-20Chromium-10Molybdenum Forgings

Molybdenum-16Iron; 35Cobalt-35Nickel-20Chromium-10Molybdenum; 35

Alpha Plus Beta Condition; Titanium-6Aluminum-4Vanadium; Titanium and Titanium-6 Aluminum-4Vanadium Alloy Powders; Titanium-6Aluminum-4 Vanadium Casting; Titanium-3Aluminum-2.5Vanadium; Titanium-6 Aluminum -7Niobium; Titanium-13Niobium-13Zirconium; Titanium-12 Molybdenum-6 Zirconium-2 Iron; Titanium-15 Molybdenum; Nickel-Titanium

The biocompatibility of any material in contact with a living tissue is part of the general context of chemical toxicity effects on the human body [5–7]. A biocompatible material may be defined as inert, nontoxic, non-mutagenic, non-recognizing,

Since the early twenty-first century, Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) [7, 10] regulates Europe's approach regarding chemical toxicology to humans, aiming to list the substances present in Europe (manufactured or imported in volumes exceeding one ton) and to control the highrisk substances while reconciling public health and environmental protection. According to the European Chemicals Agency (ECHA) [11], the list of preregistered substances contains around 143,000 chemicals. Substances that may have serious effects on human health and the environment can be identified as sub-

1.CMR group: substances which are carcinogenic, mutagenic, or toxic for

2.ED group: substances with endocrine-disrupting (ED) properties.

3.Sensitizers and other equivalent level of concern (ELoC) substances.

vPvB substances are very persistent and very bioaccumulative [12].

4.PBT group: substances that are persistent, bioaccumulative, and toxic, whereas

**200**

Among the SVHCs incriminated by ECHA, about 4000 substances which can cause a contact allergy are listed. It is estimated that 15–20% of Europe's population are sensitized to allergens. Allergic reactions are a significant and growing health problem affecting large parts of the European population [7, 13].

According to the International Agency for Research on Cancer, metals are classified into three classes:

Class 1: The agent is carcinogenic to humans—Ni derivatives, Cr6+, Cd and its derivatives, and Be and its derivatives.

Class 2: The agent is possibly carcinogenic to humans—metallic Ni and Co. Class 3: The agent is not classifiable as to its carcinogenicity to humans but reveals mutagenic properties—Sn2+, Cu2+, and Fe2+.

Metals with none or limited references as mutagens are Cu1+, Sn4+, Au, Pt, Ag, Pd, In, and G [8, 9, 14].

Corrosion is an electrochemical reaction characteristic to all metals in contact with biological systems, and its consequence is the formation of metal ions which may trigger hypersensitivity reactions and affect the immune response system [15]. It characterizes the chemical reactivity of metals and alloys, which results in a visible alteration of the material and affects the function of a metallic component or of the entire ensemble [16]. Crevice corrosion is the localized corrosion of a metal surface at, or immediately adjacent to, an area that is shielded from full exposure to the environment because of the close proximity between the metal and the surface of another material (ASTM G15-97). Tribocorrosion refers to all the mechanical and chemical interactions that cause the degradation of solids in relative displacement with or without contact lubricant.

A major characteristic that concerns any metallic material used for medical applications is good resistance to corrosion, and this is the most relevant property when it comes to its biologic safety [8]. The tendency of a metal to corrode is given by its electrode potential.

Conceived for a biological environment, alloys for medical use should essentially be integrated without developing adverse effects, maintaining their function without degrading within an acceptable time limit [17].

The potential systemic and local toxicity, allergy, and carcinogenicity result from releasing elements during the corrosion process. Elements such as Ni and Co are known for their high allergic potential, and prudence dictates that alloys containing these elements should be avoided as much as possible. Several elements are known mutagens, and a few, such as Be and Cd, are known carcinogens in different chemical forms [17].

The potential negative effects on the tissues or on the body at cellular level are precisely induced by the presence of certain components released as degradation products, especially metal cations in solution, due to surface corrosion [9]. The degradation of metallic devices in a biological environment is accompanied by the release of cations such as Cr, Co, Ni, and Ti. Therefore, we deal with a cumulative effect: allergic, irritating, mutagenic, and toxic [7].

Metal ions and debris have been shown to be released from orthopedic implants which are made of stainless steel and Co-Cr alloys [18].

Cr, Mo, Si, Fe, and Mn are the ions released from stainless steel implants, while Ti, Al, V, and Nb are released from titanium alloy implants [19]. The in situ degradation of an implant decreases its structural integrity and also releases products which may trigger an adverse biological reaction [15]. Biological risks associated with the released metal ions have been identified to include those from wear debris, colloidal organometallic complexes, free metal ions, and inorganic metal salts or resulting oxides [20].

The exposure to a variety of chemicals is known as the "cocktail effect" and expresses the way in which different chemicals are released from different sources and affect humans [7, 21]. Individual chemicals can become more dangerous when mixed together and act as an aggravating factor [22].

About 10%–15 female European adults and 1–3% male European adults suffer from Ni contact allergy. Because this is considered an important health problem, the European Union (EU) legislated this matter as follows:


In dentistry, the percentage of females allergic to Ni is reported to vary from 9 to 20%, and in case of orthodontic patients with pierced ears, 30% are allergic to Ni, Cu, and Cr [2]. In certain countries, nickel-based, cheaper alloys have increasingly been subjected to more and more regulations or even banned [25]. However, piercing of other parts of the body has increased in the last years [26].

Today we find ourselves with a Ni "cocktail effect," in an allergic population, pierced, tattooed, and with orthodontic devices made of poor stainless steels. The presence of an orthopedic implant, especially a failed metal one, has been shown to predispose patients to dermal sensitivity when compared with the general population [27].

A part of the orthopedic implants is made of alloys which contain Cr, mainly used as an alloying element in steels, where it contributes to hardness, tempering, and resistance to oxidation. Such implants will release Cr ions. Because of the increasing number of arthroplasies in young patients with osteoarthritis, the exposure time to the released chromium may be over 50 years in these cases. Cr6+ has been labeled as a class 1 human carcinogen by the International Agency for Research on Cancer, signifying carcinogenesis as a potential long-term biological effect in patients with Cr alloy implants [15]. The subsequent chromium ion metabolism is complex. The Cr released during the degradation of the Co-Cr, Co-Cr-Mo, or NiCr alloys is Cr3+, but it can be oxidized to Cr6+ at the cellular level. Cr6+ is mutagenic and carcinogenic; but its potential biological effects are controversial, as it is metabolized in the cytoplasm and cell's nucleus in Cr3+, which is not involved in DNA and chromosomal damage. Effects as reduction in CD8 lymphocyte levels and possible hypersensitivity reactions (ALVAL) are controversial [15].

ALVAL may represent an immunological response to metal wear debris [28, 29] which may appear in tissues around metallic implants. Such infiltration was reported absent in case of implants without Co, Cr, and Ni [28] and in metalon-polyethylene implants [30]. The toxic effects of the released metal ions and wear debris affect cells and tissues which are in the proximity and distant from the implant, as well. Histological studies carried out on tissues recovered from explanted metal prostheses revealed areas of necrotic tissue, with visible metal particles [15]. Elevated metal ion concentrations in serum [31, 32], erythrocytes [33], urine [34], whole blood [35, 36], tissue [37, 38], and organs [39] have all been reported in patients with implants [15]. Both Cr6+ and Cr3+ are described as allergens. According to ECHA 130,000 people allergic to Cr6+ are reported, and their number increases.

**203**

**Figure 1.**

*The modular prostheses used for testing.*

*Multicomponent Alloys for Biomedical Applications DOI: http://dx.doi.org/10.5772/intechopen.88250*

to present part of our research regarding titanium alloys.

**tests with crevice corrosion stimulation**

has to be considered.

reference.

**Table 1**.

corrosion environment (ASTM G15-97).

module, interlocked by a screw (**Figure 1**).

compression, applied or residual.

Titanium alloys are indicated for orthopedic implants because of the favorable combination of mechanical properties, low density, tissue tolerance, high strengthto-weight ratio, good resistance to corrosion by body fluids, biocompatibility, low density, nonmagnetic properties, and ability to join with the bone. Ti induces the formation of a fibrous tissue barrier when placed in contact with a healthy bone and facilitates subsequent bone growth. Contaminations of Ti alloys with elements like hydrogen and oxygen may occur during melting, thermic treatment, and surface hardening and must be avoided, due to their embrittling effect. Ti alloy corrosion resistance is superior to that of stainless steels [4]. This is the reason why we decided

**2. Resistance evaluation of titanium alloys to cyclic fatigue by dynamic** 

The role of biomaterials is to aid or totally replace the functions of living tissues. In case of orthopedic implants, the loading response has to match the natural bone. The average load on a hip bone, estimated to be thrice the body weight, may increase to a value of 10 times the body weight during heavy exercise [15]. Therefore, the ideal orthopedic implant should manifest appropriate mechanical properties and be highly biocompatible with existing tissues [40]. In case of a metallic implant, the potential corrosion of the material in the body environment

Corrosion fatigue is defined as the process in which a metal fractures prematurely under conditions of simultaneous corrosion and repeated cyclic loading at lower stress levels or fewer cycles than would be required in the absence of the

The term cyclic dynamic test (fatigue) with crevice corrosion stimulation covers various phenomena, namely, crevice corrosion, fatigue, and tribocorrosion. The term stress corrosion (static) with crevice stimulation covers two entangled phenomena, namely, crevice corrosion and stress corrosion. Stress corrosion cracking is the result of a joint action between corrosion and a constraint of reaction or of static

The aim of our research was to assess the mechanical properties of two titanium alloys currently used for orthopedic implants, namely, Ti6Al7Nb and Ti6Al4V, as

The tested modular prostheses, type PL-06, consist of a distal and a proximal

Two sample series were used for testing. The main characteristics are given in

*Multicomponent Alloys for Biomedical Applications DOI: http://dx.doi.org/10.5772/intechopen.88250*

*Engineering Steels and High Entropy-Alloys*

mg/cm2

tion [27].

controversial [15].

number increases.

30, 1994) [23] and

mixed together and act as an aggravating factor [22].

European Union (EU) legislated this matter as follows:

The exposure to a variety of chemicals is known as the "cocktail effect" and expresses the way in which different chemicals are released from different sources and affect humans [7, 21]. Individual chemicals can become more dangerous when

About 10%–15 female European adults and 1–3% male European adults suffer from Ni contact allergy. Because this is considered an important health problem, the

a."the Ni release from parts in direct contact with the skin must be lower than 0.5

In dentistry, the percentage of females allergic to Ni is reported to vary from 9 to 20%, and in case of orthodontic patients with pierced ears, 30% are allergic to Ni, Cu, and Cr [2]. In certain countries, nickel-based, cheaper alloys have increasingly been subjected to more and more regulations or even banned [25]. However, pierc-

Today we find ourselves with a Ni "cocktail effect," in an allergic population, pierced, tattooed, and with orthodontic devices made of poor stainless steels. The presence of an orthopedic implant, especially a failed metal one, has been shown to predispose patients to dermal sensitivity when compared with the general popula-

A part of the orthopedic implants is made of alloys which contain Cr, mainly used as an alloying element in steels, where it contributes to hardness, tempering, and resistance to oxidation. Such implants will release Cr ions. Because of the increasing number of arthroplasies in young patients with osteoarthritis, the exposure time to the released chromium may be over 50 years in these cases. Cr6+ has been labeled as a class 1 human carcinogen by the International Agency for Research on Cancer, signifying carcinogenesis as a potential long-term biological effect in patients with Cr alloy implants [15]. The subsequent chromium ion metabolism is complex. The Cr released during the degradation of the Co-Cr, Co-Cr-Mo, or NiCr alloys is Cr3+, but it can be oxidized to Cr6+ at the cellular level. Cr6+ is mutagenic and carcinogenic; but its potential biological effects are controversial, as it is metabolized in the cytoplasm and cell's nucleus in Cr3+, which is not involved in DNA and chromosomal damage. Effects as reduction in CD8 lymphocyte levels and possible hypersensitivity reactions (ALVAL) are

ALVAL may represent an immunological response to metal wear debris [28, 29] which may appear in tissues around metallic implants. Such infiltration was reported absent in case of implants without Co, Cr, and Ni [28] and in metalon-polyethylene implants [30]. The toxic effects of the released metal ions and wear debris affect cells and tissues which are in the proximity and distant from the implant, as well. Histological studies carried out on tissues recovered from explanted metal prostheses revealed areas of necrotic tissue, with visible metal particles [15]. Elevated metal ion concentrations in serum [31, 32], erythrocytes [33], urine [34], whole blood [35, 36], tissue [37, 38], and organs [39] have all been reported in patients with implants [15]. Both Cr6+ and Cr3+ are described as allergens. According to ECHA 130,000 people allergic to Cr6+ are reported, and their

b."all metallic parts that are inserted into pierced ears and other parts of the human body must not have a nickel release rate greater than 0.2 mg/cm<sup>2</sup>

(Commission directive 2004/96/EC of September 27, 2004) [24].

ing of other parts of the body has increased in the last years [26].

/week" (European Parliament and council directive 94/27/EC of June

/week"

**202**

Titanium alloys are indicated for orthopedic implants because of the favorable combination of mechanical properties, low density, tissue tolerance, high strengthto-weight ratio, good resistance to corrosion by body fluids, biocompatibility, low density, nonmagnetic properties, and ability to join with the bone. Ti induces the formation of a fibrous tissue barrier when placed in contact with a healthy bone and facilitates subsequent bone growth. Contaminations of Ti alloys with elements like hydrogen and oxygen may occur during melting, thermic treatment, and surface hardening and must be avoided, due to their embrittling effect. Ti alloy corrosion resistance is superior to that of stainless steels [4]. This is the reason why we decided to present part of our research regarding titanium alloys.
