CHAPTER 2

LITERATURE SURVEY

Metallic biomaterials are of great interest due to their higher mechanical

properties. Metallic materials have very high tensile strength, fatigue

strength, and fracture toughness as compared to ceramics and polymers.

Due to these key properties, metallic materials are the widely used

biomaterials for replacing the structural parts of the human body. Some of

biomedical applications where metallic biomaterials are widely used are

dental implants, artificial heart valves, bone plates and screws, artificial

joints, intramedullary nails, spinal fixations and spacers, pace maker cases,

external fixtators, wires and stents. Many metallic biomaterials have been

proposed which include stainless steels, cobalt based alloys, commercially

pure titanium, and titanium alloys (Sumita et al., 2004; Patel & Gohil,

2012).
2.1. STAINLESS STEELS:

Implants were initially produced from pure metals. Pure metal implants

often showed poor corrosion resistance as well as poor mechanical

strength. Stainless steels were then introduced in 1920s to solve the

corrosion problems. W.H. Hatfield used 18/8 stainless steel that showed

good corrosion resistance and mechanical strength resulting long-term

medical use. The post-surgery complications, the number of implant

failures, and sensitivity problems were considerably lowered with the use

of stainless steels. In stainless steels, high corrosion resistance was

achieved due to the presence of chromium, nickel and molybdenum and

other alloying elements (Uhthoff et al., 2006; Hatfield, 1931).

Stainless steel of 316 and 316L grades are commonly used for biomedical

applications. ASTM recommended grade 316L for making implants due to

low carbon content. The lower carbon content reduces the formation of

chromium carbide that may generally result in increased intergranular

corrosion. Therefore, lowering the carbon content is useful for making

stainless steel more corrosion-resistant (Ismail et al., 1999).

 Figure: 2.1 : Stainless steel implants used in biomedical applications

(Ismail et al., 2017)

Conventional stainless steels shows high corrosion resistance was achieved

due to the presence of chromium, nickel and molybdenum and other

alloying elements. Conventional stainless steels are suitable for high load

bearing applications. As the name implies, Nickel-free stainless steels do

not contain any Nickel content, which may result in increased corrosion

resistance and reduced stress corrosion and biocompatibility. Nickel

produces metal allergic problems like erythema, rash and granuloma in

patients. The trend of metal allergy to Nickel content is increasing and it is

therefore necessary to eliminate the use of nickel in stainless steel.

Nitrogen is generally alloyed with stainless steel to form Ni-free stainless

steel while maintaining very low Nickel content. Nitrogen is chosen

because of its nonmagnetic nature. Despite the fact that stainless steel is

less corrosion-resistant and biocompatible as compared to titanium, the risk

of corrosion is minimized in the oxygen-rich environment, thus enabling

stainless steels more suitable and more affordable material for stents

(Ducheyne & Kohn, 1998; Navarro et al., 2008; Disegi & Eschbach, 2000;

Kanerva et al., 2001; Rondelli et al., 2005).

Nickel-free stainless steels are produced by various methods including

melting methods, such as, electroslag remelting, pressurized electroslag

remelting, counter-pressure casting, and solid nitrogen absorption. These

methods uses large amounts of Nitrogen and Manganese (austenite

stabilizers) instead of Nickel to form Nickel-free stainless (Niinomi et al.,

2012). Some of the nickel-free stainless steels are Fe–(15–18)Cr–(10–

12)Mn–(3–6)Mo–0.9N (Uggowitzer et al., 1996), Fe–18Cr–18Mn–2Mo–

0.9N (Menzel et al., 1996), Fe–15Cr–(10–15)Mn–4Mo–0.9N (Menzel et

al., 1996), Fe–17Cr–10Mn–3Mo–0.49 N–0.2C (Thomann & Uggowitzer,

2000), Fe–21Cr–9Ni–3Mn–0.41N (Rex734) (Thomann & Uggowitzer,

2000), Fe–(19–23)Cr–(21–24)Mn–(0.5–1.5)Mo–0.9N (BioDur108)

(Walter, 2006), and Fe–(16–20)Cr–(12–16)Mn–(2.5–4.2)Mo–(0.75–1)N

(X13CrMnMoN18–14-3) (Koch et al., 2002).

The corrosion resistance, biocompatibility and osseointegration of stainless

steels are poor as compared to titanium alloys. However, the cost of

stainless steels is relatively less as compared to titanium. Furthermore,

stainless steels exhibit relatively sufficient mechanical properties as well as

ductility. Complete tissue regeneration is possible with stainless steel and is

the material of choice for screws, nails, and fracture plates that provide

temporary support (Sumita, 1997; Frame, 2016).

Stainless steel is majorly used in orthopedic and trauma surgery, mainly

because of the stiffness requirements. Also, because of the ductility of

stainless steel which is higher than that of titanium, stainless steels are

favourable for makeing contouring plates ealily as compared to titanium

plates. Reconstruction plates are therefore made of stainless steels for

acetabular surgery, pelvic surgery and surgeries at other anatomical

locations (Ganesh et al., 2005; Frosch & Sturmer, 2006).

2.2. COBALT BASED ALLOYS

Cobalt alloys show high wear resistance in addition to better mechanical

strength, high elastic modulus, high abrasion resistance and high corrosion

resistance when compared to those of stainless steels. In stainless steels,

addition of chromium increases the corrosion resistance. Cobalt itself can

resist corrosion and, in the case of cobalt alloys, cobalt-chromium based

alloys are considered to possess excellent corrosion resistance. Because of

high corrosion resistance and outstanding mechanical strength, they are use

in applications like removable partial dentures and orthopaedic implants.

However, biocorrosion is one of the major drawbacks of this kind of alloys,

which can cause adverse effects. Co-Cr-Mo alloy is used for femoral head

of joint prostheses along with polyethylene cup (UHMWPE) due to its high

wear resistance and corrosion resistance. However, metal ions released over

many years may lead to toxic issues. Co-29Cr-6Mo-1Ni alloy is one of the

biomaterials approved by ASTM, which contains 1 mass% of Ni. However,

the Nickel and Cobalt ions are responsible for inducing allergic reactions.

Hence, Co-Cr-Mo alloy may be prepared without Nickel, which may solve

the toxicity problem in cobalt nickel based systems (Dong et al., 2003;

Sargeant & Goswami, 2006; Sachiko et al., 2005; Prasad et al., 2017; Stohs

& Bagchi, 1995; Basketter et al., 1993; Uggowitzer et al, 1996; Chiba et

al., 2005).

Cobalt-Chromium alloys possess higher elastic modulus, density and

stiffness as compared to natural bone. This results in higher stress shielding

as compared to those of Titanium alloys or Magnesium alloys. The

biocompatibility and osseointegration of Cobalt-Chromium is also lesser

than that of Titanium. Due to these reasons, in clinical practice, Cobalt-

Chromium alloys are employed for applications where there is no direct

contact or interface with the natural bone. Titanium can be used where

direct contact is required with the bone. Yet, Cobalt-Chromium alloys can

give rise to metal corrosion and shredding (Li et al., 2014; Nayak et al.,

2016). Cobalt-chromium alloys release toxins in the wet and salty

environment and this release of toxins in turn may lead to formation of

cancerous tumors. Even though the number of tumors is lower near the

implant site, the released ions could exist at other parts of the human body

(Geetha et al., 2010).

2.3. PURE TITANIUM AND TITANIUM ALLOYS

Titanium has high strength-to-weight ratio, excellent biocompatibility and

excellent corrosion resistance to most human body environments. Both

pure titanium and titanium alloys were used for biomedical applications.

Titanium alloys show higher strength-to-weight ratios as compared to pure

titanium. Ti6AL4V alloy is one of the popular titanium alloys used for

implant material. Ti6AL4V is a dual phase (α + β phases) alloy that shows

much higher tensile strength as compared to pure titanium. But, the

titanium alloys show lower resistance to pitting corrosion than pure

titanium. Such corrosion can cause early inflammatory response after an

implant is inserted. However, the overall corrosion resistance of titanium

alloys is better than that of stainless steels and cobalt-chrome alloys

(Blackwood, 2003).

Since the time the bone plates and screws were introduced in 1965, pure

titanium and titanium alloys have been the attractive metallic materials

used for biomedical applications. Ti–6Al–4V alloy has been used for

biomedical application for a long period. Other alloys of titanium, such as

Ti-29Nb-13Ta-4.6Zr, Ti-Fe-Ta, Ti-Hf, Ti-Zr-Nb-Ta, Ti-Ta, Ti–6Al–7Nb and

Ti–5Al–2.5Fe have also been recently developed due to the toxic effects of

vanadium in the Ti–6Al–4V alloy (Frosch & Stürmer, 2006; Wang, 1996;

Niinomi, 1998; Elias et al., 2008; Milošev, 2010; Niinomi et al., 2005).

Figure: 2.2 : Titanium implants used in dental applications (Elias et al.,

2008)
Pure Titanium does not become hard for load-bearing applications.

Therefore, pure titanium is popularly used in dental applications, acetabular

shells, and as coating material in joint replacements. Titanium alloys (Ti–

6Al–4V and Ti–6Al–7Nb) show high compression strength as compared to

pure titanium and are commonly found in orthopaedics (Milošev, 2010).

Though titanium alloys show excellent corrosion resistance and

biocompatibility, they are not regarded as the perfect implant material.

They have poor shear strength, leading the metal unsuitable for implant

screws. High coefficient of friction of titanium produces wear particles if

rubbing against the natural bone or another implant surface. Due to high

coefficient friction also cause fretting corrosion (Blackwood, 2003).

Biocompatibility of titanium alloys is the highest among the metallic

materials. However, they are not bioactive. Hence, titanium alloys are

modified using surface modification with the help of bioactive materials

(for example, ceramics) to improve the biocompatibility (Niinomi, 2007).

2.4. MAGNESIUM ALLOYS

Temporary implants are kept for a shorter period. Once the fractured bone

tissue grows, they are usually removed. When the orthopaedic joints, such
as spinal, shoulder, hip, knee, and ankle affected by arthritis or parts

fractured severely in accident or disease, permanent implants are kept in

place of the entire joint after a arthroplasty surgery. Magnesium has been

one of the suitable biomaterial in temperary implants. Magnesium is one of

the fourth most abundant element present in the human body, and the

release of metal does not affect the human metabolism. It is a a cofactor for

many enzymes and is considered to stabilise the DNA and RNA structures.

Magnesium has low density and Young's modulus close to natural bone and

high fracture toughness as compared to the ceramic material, which makes

magnesium to a suitable alternative to most metals and ceramics for

temperaroy implants. It can be dissolved after the healing process is over.

Mg can be used as biodegradable material to treat blockage in the coronary

artery and/or other circulatory systems ossie, to treat patients suffering

from cleft palate, and to rectify the deformities of long bones, to overcome

the limb length problems (Manivasagam & Suwas, 2014; Agarwal et al.,

2016).

Magnesium shows high specific strength, low elastic modulus (41 GPa)

and low density (1.74 g/cm3), whose properties are closer to those of

natural bone. Due to the closer values, the risk of stress shielding is very

low in magnesium biomaterials. Magnesium can be used to form variety of

biomaterials, such as screws, rods and metal plates. It provides mechanical

support but gradually degrade. As the wound heals, this gradual

degradation provides the space for the growing tissues. As the material

degrades, the implants will fully be degraded and removed from the body.

This degradation minimises the chance of metal-related sensitivity that is

usually observed in the case of Stainless steels, Titanium and Cobalt

implants (Persaud-Sharma & McGoron, 2012; Sanchez et al., 2015; Shih et

al., 2002; Kirkland et al., 2012; Song & Song, 2007).

2.5. OTHER METAL ALLOYS

Zn and Zn-based alloys have also been used in biomedical use. Daily

human zinc requirement is approximately 15 mg and Zinc deficiency can

result in problems, such as growth failure, neuropathy, impaired parturition

(dystocia), decreased or increased food intake, hair loss, diarrhea,

dermatitis, hypotension and hypothermia. Pure Zn has relatively lower

strength (below 20 MPa) and plasticity (0.2% elongation). Zinc Alloys,

with alloying elements, such as Mg, Ca and Sr increase the mechanical

strength considerably and are used in biomedical applications (Li et al.,

2015)
Nickel-titanium alloy, also called Nitinol, is a smart biomaterial with shape

memory properties as well as superelastic properties. Its Young's modulus

is close to natural bone, but is different from other metal and alloys. Nitinol

is used in orthodontics, bone fractures, bone suture anchors, and stents etc.

NiTi shows excellent biocompatibility as there is a formation of a thin

titanium oxide surface and are used. and Nitinol is highly stable in the body

with minimal Ni release. Addition of Cu to Nitinol (TiNiCu) further

provides better fatigue and modified shape memory properties (Minnath,

2018).

Magnetic susceptibilities of the metals and living tissues another property

one may have to look into. The magnetic susceptibility of living tissues is

9x10-6 cm3/g, where as Ti has 3.2x10-6 cm3/g and Zr has 1.3x10-6 cm3/g.

It is noted that Ti has the value of magnetic susceptibility considerabley

lesser as compared to ferromagnetic metals like Fe and Co. Therefore, Zr

can be employed in biomedical applications where the devices should not

be have magnetic properties. Some of the common Zr alloys include Zr-Nb

alloys, Zr-3Nb, Zr-6Nb, and Zr-9Nb, Zr-Mo alloys and Zr-3Mo (Minnath,

2018; Nomura et al., 2009; Kondo et al., 2011; Suyalatu et al., 2011).
Figure: 2.3 : Historical development of metal based amorphous alloys or

bulk metallic glass (Ibrahim et al., 2017)

Bulk Metallic Glass (BMG) first introduced in 1950’s by rapid cooling rate

(104-107 °C/s) from vapour phase of a metal or liquid phase. They possess

superior mechanical properties, wear resistance, biocompatibility and

corrosion resistance. They do not have specific crystal structures unlike

conventional metals. BMGs are obtained through different techniques, such

as electrodeposition, ion implantation or mechanical alloying. The

historical development of BMGs is shown in figure. BMGs can be

categorized as biodegradable (Mg, Ca, and Zn based BMGs) and non-

biodegradable (Fe, Ti, and Zr based BMGs). Due to their superior

properties, Fe, Ti, Zr based BMGs have the potential for replacing stainless
steel, Ti, and Zr alloys (Ibrahim et al., 2017; Yi et al., 2017; Espallargas et

al, 2013; Li et al., 2016; Liu et al., 2013; Wang et al., 2008; Hench, 2016).

2.6. FACTORS AFFECTING THE CHOICE OF A METAL AS

BIOMATERIAL

Metallic materials have been often used for biomedical use due to their

superior mechanical properties and high corrosion resistance to body fluids.

Mechanical properties (Toughness, elasticity, and rigidity), and electrical

conductivity are considered as the important properties for metallic

materials to be used in biomedical devices. In general, metallic materials

are the first choice for orthopedic implants, bone fixators, external fixators,

artificial joints, etc., because they are strong enough in the growth of the

hard tissues in orthopedics. Similarly, in the case of stents and stent grafts,

they are kept at stenotic blood vessels to dilatation, where elasticity and

rigidity are important for maintaining dilatation. Therefore, metallic

materials must be used where mechanical reliability and safety are

important, and cannot be replaced with other materials, such as ceramics or

polymers. Corrosion-resistant metals, such as titanium, titanium alloys, Co-

Cr-Mo alloy and stainless steel are largely employed in biomedical

applications. Metallic materials are also used in cardiovascular devices and

other biomedical applications. But they do have several problems when

used as a biomaterial. Toxicity of corrosion products, lack of

biocompatibility, release of metal debris to the human body, fracture and

fretting due to corrosion fatigue and poor adhesion with body cells and

tissues are considered as some of the major problems of using metallic

materials (Sumita et al., 2004; Niinomi et al., 2005; Pound, 2004; Hench,

2002).

Biomaterials are majorly used in places where the materials make contact

with human live tissues. Therefore, interactions between the implant

material surfaces and human tissues must be clearly understood before use.

The selection of the biomaterials is based on the number of factors, as

follows.

2.6.1 Corrosion Resistance to Body Fluids:

Corrosion is the loss of metallic ions which is released from metal implants'

surface to the surrounding body environment. There are several types of

corrosion. Crevice corrosion occurs when metallic ions dissolve and create

positively charged localized regions like screw implant and bone interface.

Pitting corrosion occurs when metallic ions dissolve and combine with

cloride ions to form pits on the surface of the implants. Galvanic corrosion

occurs when there is a difference in electrical gradients. Electrochemical

corrosion occurs when anodic oxidation and cathodic reduction result in

metal deterioration due to electron transfer (Saini, 2015; Lemons & Lucas,

1986; Blackwood, 2003).

Biomaterials, implanted within the human body, make contact with the

extracellular body fluids (blood, interstitial fluid etc.), which may corrode

these biomaterials. The pH values within the body changes due to the

presence of body fluids. The pH of blood and interstitial fluid vary usually

from 7.35 to 7.45. During implantion, the pH values may decrease up to

about 5.2 in the hard tissues, and it takes about 2 weeks to recover the pH

values to about 7.4. Therefore, abrupt decrease in the pH value may have

only little effect on corrosion. However, one has to worry about the the

tendency of corrosion by body fluids in long time and their effect on

toxicity and allergy of the implanted biomaterials. If the metallic ions are

released by the biomaterials into the body fluid, and combine with other

biomolecules (proteins and enzymes), the effects are very serious.

Therefore, corrosion resistance of metallic biomaterials is highly important

to be determined (Hanawa, 2009).

In terms of corrosion resistance, 316L stainless steel are considered to be

inferior as compared to titanium alloys and cobalt–chromium alloys. 316L

stainless steel used as orthopedic implants corrodes in the human body

environment and releases metal ions of iron, chromium, and nickel.

However, due to low cost of metal, 316L stainless steel is largely used for

implant devices (Sumita et al., 2004).

2.6.2. Nontoxicity:

Before selecting a biomaterial, one has to primarily see whether the

elements of the biomaterials contain any nontoxic metal. Refering the

cytotoxicity of metals is necessary for this purpose. Some examples of

cytotoxicity data are shown in the figure, in which the relative growth rate

of L-929 cells of various pure metals and their coefficient of fibroblastic

outgrowth are presented. Another figure shows the data on corrosion

resistance and biocompatibility of some of the pure biometals and

biocompatible metallic materials (Niinomi, 2002).

2.6.3. Metal Release:

Since the orthopaedic implants may release metal into body fluids, such as

serum, urine, etc., the toxic effects of metal release is an important subject

to be reviewed. Metal release is caused by various mechanisms, such as

corrosion, wear and mechanically accelerated electrochemical processes.

Excess metal release may lead to failure of clinical implant, osteolysis,

remote site accumulation and cutaneous allergic reactions. Implants that

used Cobalt based alloys were reported to release elevated amount of Co,

Cr and Ni metal release into in body fluids. The use of Ti–6Al–4V alloy for

implants releases vanadium that has toxic effects (Okazaki & Gotoh, 2005).

Figure 2.4: Cytotoxicity of pure metals by considering only the relative

growth rate of L-929 cells (Niinomi et al., 2002)

The metals released into human body may have many ill-effects. Nickel

affects the human skin (for example, dermatitis); Cobalt can produce

Anemia B inhibiting iron from being absorbed into the blood stream;

Chromium can cause ulcers and disturbances in the central nervous system;

Aluminum can cause epileptic effects and Alzheimer’s disease; and,

Vanadium can produce toxic effects in the elementary state (Aksakal et al.,

2004).

Figure :2.5: Relationship between polarization resistance and

biocompatibility of commonly used biometals (Niinomi et al., 2002)

2.6.4. Metal Allergy:

Metal allergy is now-a-days considered as another significant problem in

selecting a biomaterial. For example, figure shows a trend of Nickel metal

allergy in Europe. It was found that Nickel allergy affected about 20% of

young females and 4% of young males in Europe. Metallic ions released

from a pure metal or its alloy causes metal allergy. In dentistry, the most

common materials that caused metal allergy wer Cobalt, Chromium, and

Nickel. Such metallic elements should be omitted for biomaterial

applications (Niinomi et al., 2002). Some of metals and the metal allergy

caused by them are shown in the figure.

Figure: 2.6: Nickel metal allergy reported in the Europe (Niinomi et al.,

2002)
Figure: 2.7: Percentage of metal allergy caused by the metallic elements

(Sumita et al., 2004)

Release of nickel ions can cause allergy and cancer. The International

Agency for Research on Cancer (IARC) says that nickel compounds are

generally carcinogenic, and therefore pure nickel and nickel alloys are also

possibly carcinogenic. In medical practice, less than 0.2% is considered to

be congruous, and reduction of nickel content lower than 0.2% will

produce nickel-free alloys with additional costs. However, the reliability of

such implants is not assured. There is no clear report supporting the lower

nickel content to be not toxic to the human body. The European Parliament

also raised concerns about the increasing trend of nickel toxicity.

Significant amount of nickel can be found in some cobalt–chromium

alloys, although they are currently approved for surgical use (Sumita et al.,

2004).

Table 2.1: Metal tolerances in human body (Leng, 2005)

The human body contains the metallic elements, such as, iron, manganese,

magnesium, zinc, etc., in trace amounts. Therefore, these metallic elements

are essential for normal biological functions of the body. However, the

body is tolerant only for a smaller amounts of the presence of these

materials. Excessive amounts of these elements can cause toxic reactions in

the body. Hence, the released metal ions from the metallic implants may
lead to local inflammation, mutation (mutagenesis), or even cancer

(carcinogenesis). The tolerances of the human body to some of the common

metal elements used in metal implants are listed in the table.

2.6.5. Reliability:

The reliability of the implants is determined by fracture and wear after

implantation. The mechanical properties, such as fatigue, wear and

toughness, of biomaterials should be evaluated in the living body

environments; the evaluation of these properties is essential for confidently

using the implants with more reliability in long run. Figure shows the

fatigue strength in air of commonly used biomaterials, such as stainless

steel, cobalt based alloys and titanium based alloys, and natural bone. To be

used as biomaterial, it is essential to determine the fatigue strength of these

biomaterials in human body environment. The fatigue values decreases in

the order given by: Cobalt based alloy > Ti based alloys > 316L stainless

steel. From the values of fatigue strength, it can be seen that the fatigue

limits are determine by various factors, such as surface condition,

fabricating process and fatigue condition. It is also important to note that

the fatigue limits of all metallic biomaterials shown are very much higher

than that of natural bone (Niinomi, 2007).

 Figure: 2.7: Fatigue strength at 107 cycles of common biomaterials and

bone (Niinomi, 2007)

2.7 LIMITATIONS OF CURRENT METALLIC BIOMATERIALS

Nickel, Chromium, and Cobalt present in both stainless steel and Cobalt-

Chromium alloys produced cytotoxic effects. Nickel toxicity causes

dermatitis and the metal ions released into human body create allergic

effects. Aluminium and Vanadium ions in Titanium alloys cause

Alzheimer’s disease, neuropathy and osteomalacia in long term use. Cobalt

could cause carcinogenic effects. Metals of high friction coefficient can

produce more wear debris that causes inflammatory reaction loosening the

implants due to osteolysis. High modulus of elasticity of metals causes

stress shielding leading to implant failure (Hussein et al., 2015). Metallic

implants, when degraded, releases metallic debris, as nanoparticles and

solubilised ions. These nanoparticles can produce mechanical wear and the

solubilized ions can cause corrosion (Soto-Alvaredo et al., 2014).

Biomedical metals having some degree of toxicity can affect the body and

can accumulate with other parts of the body. Molebadynm and Neobium

debris can be accumulated in brain and lungs after releasing. Certain

implants containing Ag, Cr, Fe, Mo, Ni and Ta exhibit metallic debris in

human body tissues. Co, Cr, Sb and Sc also can accumulate in other human

organs, such as heart, kidney, liver and spleen. A 100 times increase of

blood Co and Cr levels is possible with the implants releasing these

elements. Higher levels of Ni, Ti, and V also have failed the total joint

replacements. Co is distributed in the blood cells and plasma which shows

that it is absorped by the human body. Co, Cr, and Mo were also absorped

by the human body and transported to other parts. These metal ions were

detected in hair strands and urine of patients that can generate abundant

debris (Matusiewicz, 2014).

Co, metallic Ni, Ni/Cr alloys and Pb are potentially carcinogenic in nature

to the human body. The release of these metals can rarely causes Tumour

generation is rare, and the potential of tumour growth depends on the

amount of carcinogenic metals released into the body. Interaction of these

metals with human body could create metal sensitivities, or allergies. These

are majorly reported in orthopaedics, vascular and dental implants. Release

of Ti particles releases inflammatory cytokines that initiate osteolysis along

the bone/implant interface (Davidson et al., 2007).

Stainless steels, Cobalt alloys and titanium alloys are used for permanent

implants and they should be removed once the healing is done. The

removal of implants is normally carried out with a second surgery. For

example, though titanium alloys have high corrosion resistance, high

biocompatibility, high strength-to-weight ratio, and low elastic modulus,

titanium implants have high elastic modulus which is different from its

surrounding bone tissues. This mismatch may lead to stress-shielding

phenomena where stress is imparted on the bone–implant interface leading

to implant loosening, bone resorption and even implant failures (Xin et al.,

2011; Huang et al., 2015).

Metallic implants are also susceptible to bacterial infection. Metallic

implants highly affect the local defense system and can cause the surgical

trauma after implantation. The reduced defence mechanism can be

favourable for colonization of bacteria leading infection. The use of

metallic implants, therefore, creates complications like prolonged

hospitalization, implant failure, removal of implants, financial burden, and

even death. Hence, preventive measures are needed to prevent implant-

induced bacterial infections (Zhao et al., 2009; Kasemo, 1983).

Mg-based alloys, Fe-based alloys, and Zn-based alloys are some of the

most efficient degradable metals used in biomedical implants. These metals

are essential substances for human body. The recommended intake of

magnesium is about 240-420 mg/day; it is 8-18 mg/day for iron (17-50

times lower than that of magnesium); and it is 8-11 mg/day for zinc (30-40

times lower than that of magnesium). It is important to note that overdose

of these metals may cause the adverse effects in human body. The elastic

modulus of natural bone is about 3-20 GPa, while it is about 43 GPa for

Magnesium, 211.4 GPa for iron and 90 GPa for zinc, respectively. The

mismatch of elastic modulus in iron and zinc may cause stress shielding.

Both pure iron and pure magnesium are good candidates in terms of

biocompatibility. However, iron accumulates and retains the corrosion

products over 9 months which may prevent the tissue growth. Elastic

modulus of magnesium is very close to that of natural bone. Magnesium

implants were proven to stimulate the new bone formation from the time

they are implanted (Chen et al., 2014; Zheng et al., 2014; Li et al., 2014).

Although magnesium has good mechanical and biological properties, the

rapid corrosion rate in human body environments is high leading to large

amounts of magnesium ions being released. The release of magnesium

causes premature loss of mechanical strength and failure of the implanted

material (Brar et al., 2009; Kirkland et al., 2012; Atrens et al., 2011;

Bazaka et al., 2014)

2.8 SURFACE MODIFICATION TO OVERCOME THE PROBLEMS OF

METALLIC BIOMATERIALS AND THE RESEARCH GAP:

Most of the metallic biomaterials do not meet the requirements in terms of

both surface and bulk properties for biomedical applications. An effective

way for making a clinically appealing biomaterial is surface modification

which can bring biofunctionality of the surface and bulk properties of the

base metal (Ikada, 1994; Mohammed et al., 2014).

The bulk properties of a biomaterial determine the biological performance

of the material for a biomedical application. The mechanical properties,

such as, elastic modulus, ultimate tensile stress, etc. provide sufficient

support for the applied mechanical loads. The biological response, on the

other hand, is determined by the surface properties, such as protein

adsorption or activation, cell adhesion and host responses to materials. The

physicochemical properties of the material surface determine the biological

events. For example, blood compatibility (i.e., protein adsorption, platelet

adhesion, thrombogenicity, patency). Most metals show poor

biocompatibility and hence the surface modification of biomaterial may be

considered to the promising route to enhance the biofunctionality to

modulate the biological responses without changing the bulk properties of

the metallic biomaterials (Agarwal, & García, 2019; Anderson et al., 2008).

Surface modifications can be carried out by different techniques, such as

Chemical Treatments, Ion Beam Implantation, Silanization and Langmuir–

Blodgett Deposition, Self-assembled Monolayers, Microcontact Printing,

Coatings, Texturing, Laser surface engineering, Laser-assisted Coatings,

Laser Texturing, bow tie scanning, synchronized with image scanning,

laser-induced forward transfer (LIFT), Matrix-assisted pulsed-laser

evaporation direct write (MAPLE DW), etc. (Kurella & Dahotre, 2005;

Roach et al., 2007; Chu, 2002; Chu, 2013; Bagno & Di Bello, 2004)

Hydroxyapatite (Ca10(PO4)6(OH)2) is one of the biocompatible ceramic

used for biomedical applications, majorly as a coating material. It is

basically pure calcium phosphate, having favorable osteo-conductive and

bioactive properties suitable material for both dental and orthopedic

applications. It is also very important to note that the chemical composition

and crystal structure of HA is very close to the apatite formed in the human

skeletal system. Therefore HA has become one of the most suitable

materials for bone substitution and reconstruction. Hydroxyapatite can be

synthesized through various techniques such as precipitation, hydrolysis,

and hydrothermal synthesis or it can be extracted from natural resources,

such as fish bones, seashells, eggshells, bovine bones and shrimp shells

(Mohseni et al., 2014; Vahabzadeh et al., 2015; Thomson et al., 1998;

Deligianni et al., 2000; Szcześ et al., 2017..

HA is one of the widely used coating materials in orthopedic and dental

applications due to its superior biocompatibility and strong bonding with

human bones. The traditional HA coated bioceramics, however, show poor

mechanical strength and promote bacterial growth which in turn may be the
reasons for implant rejections. Addition of elements, having antibacterial

properties, such as silver (Ag), zinc (Zn), copper (Cu), cerium (Ce),

samarium (Sm), etc., may be beneficial to effectively prevent bacterial

infections (Sathishkumar et al., 2016; Fihri et al., 2017).

In the bone surgery, osseointegration is an important and desirable goal,

and HA coated implants show high efficiency. However, the coating

parameters such as location, composition, uniformity, thickness, etc. can

influence the efficiency and robustness of HA coating [18]. There are

mixed reports in favour or against HA coating on dental implants in terms

of long-term survival of implants (Goodman et al., 2013).

In the work of Lee et al. (2000), meta-analysis was performed to resolve

the controversy on the reliability of HA coatings to dental implants. The

survival rates of HA coated implants varied from 93.2% to 98.5%, for a

period of 4 to 8 years of follow-up, while they varied from 79.2% to

98.5%, for the period of 5 to 8 years of follow-up. The survival rates

remained above 90% and showed high reliability of HA coatings in dental

implants. Similar work was done by Herrera et al. (2015) and concluded

that the HA coated implants showed high survival rates compared to other

implants.
HA coatings were evaluated on various substrates by research community.

HA coating can be done using various coating techniques, such as plasma

spraying, pulsed laser-deposition, sputtering, sol–gel, electro-deposition,

electrophoresis etc. Among these techniques, electro-deposition of HA is

regarded as an inexpensive and simple process that can be performed at

room temperature. The chemical composition and thickness of HA coating

can easily be controlled by appropriately modifying the electro-deposition

conditions.

In the work of Song et al. (2008), HA coating was performed on AZ91D

magnesium alloy using electro-deposition method to improve the

degradation in human body environment. The HA coating was found to

delay the corrosion rate of magnesium alloys (10 times slower than the

uncoated AZ91D) in stimulated body fluids and could provide sufficient

protection on magnesium alloys.

In the work of Shi et al. (2011), the composite coating of Ca-P was carried

out by micro-arc oxidation followed by electrodeposition on AZ80

magnesium alloy. The effect of coating on corrosion rate and apatite-

formability in simulated body fluids were investigated and the results

showed that the composite coating significantly reduced the corrosion rate

and enhanced apatite-formability of magnesium alloy.

The corrosion resistance of HA coating on porous magnesium was

investigated by Kang et al. (2013), HA coating was performed by

immersing the porous magnesium in the aqueous solution (of

ethylenediaminetetraacetic acid calcium disodium salt hydrate and

potassium phosphate monobasic in distilled water) for 6 h. The

compressive strength increased remarkably from 8 MPa to 17 MPa. It was

also found that bio-corrosion of the porous magnesium was inhibited

significantly by HA coating. Plasma spraying process is commonly used for

HA coatings for fixing implants due to extreme high temperatures.

However, they unfortunately degrade easily in a short time after

implantation, which may reduce the adhesion of HA layer.

In the work of Stoch et al. (2001), electrophoretic deposition was

successfully used for preparing the HA coating on titanium implants and

found that the process did not change the properties of HA coatings as

compared to the pure HA powder.

2.9 PROBLEMS STATEMENT

2.10 RESEARCH OBJECTIVES

2.11 ORGANIZATION OF THESIS