Accepted Manuscript

Biomedical materials and techniques to improve the tribological, mechanical and

biomedical properties of orthopedic implants – A review article

Mahmoud Z. Ibrahim, Ahmed A.D. Sarhan, Farazila Yusuf, M. Hamdi

PII: S0925-8388(17)31441-X
DOI: 10.1016/j.jallcom.2017.04.231
Reference: JALCOM 41635

To appear in: Journal of Alloys and Compounds

Received Date: 28 January 2017

Revised Date: 18 April 2017
Accepted Date: 21 April 2017

Please cite this article as: M.Z. Ibrahim, A.A.D. Sarhan, F. Yusuf, M. Hamdi, Biomedical materials and
techniques to improve the tribological, mechanical and biomedical properties of orthopedic implants – A
review article, Journal of Alloys and Compounds (2017), doi: 10.1016/j.jallcom.2017.04.231.

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 ACCEPTED MANUSCRIPT
Biomedical materials and techniques to improve the tribological, mechanical
and biomedical properties of orthopedic implants – A review article
Mahmoud Z. Ibrahima, Ahmed A.D. Sarhanb*, Farazila Yusufc*, M. Hamdid

a,c,d
Centre of Advanced Manufacturing and Material Processing, Department of Mechanical Engineering,
Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia
a
Department of Mechanical Engineering, Faculty of Engineering, Ain Shams University, Cairo 11566, Egypt

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b
Mechanical Engineering Department, King Fahd University of Petroleum and Minerals, Dhahran 31261,
Saudi Arabia
b
Department of Mechanical Engineering, Faculty of Engineering, Assiut University, Assiut 71516, Egypt

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* Corresponding Authors

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1- Ahmed A. D. Sarhan, E-mail: ahsarhan@kfupm.edu.sa, TEL: +966138602547, FAX: +966138602949
2- Farazila Yusuf, E-mail: farazila@um.edu.my, TEL: +603-7967-7633, FAX: +603-7967-5317

Abstract
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Recently, there has been an increasing trend in researches focusing on improving the performance
of the biomedical implants. The clinicians used metallic implants to treat bone imperfections and
fractures. The commonly used metals (Stainless steel, Ti-alloys and Co-alloy) failed to prove long-
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term durability and did not build sufficient bond with human bone. Since the invention of bioactive
materials, which can generate chemical bond with bones, the researchers proposed combining the
superior mechanical properties of metal and bioactivity of bioactive materials. This can be achieved
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by cladding bioactive material on metallic substrate. Different techniques, like thermal spraying,
electron magnetron sputtering, laser cladding, etc., were proposed to successfully deposit bioactive
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materials on metallic substrates. In this article, we will discuss the potential of available metallic
alloys and bioactive materials in biomedical implants including different techniques used in
depositing bioactive materials on metallic implants.
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Keywords: biocompatible metals, Bulk Metallic Glass alloys, bioactivity, coating techniques, Bioglass,
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Hydroxyapatite
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1. Introduction
The development of medical implants is of great importance to treat bone fractures and deficiencies.
The need for implants increased dramatically in the past 5 years (the number of revision hip surgery
increased by 26% and is predicted to reach 137% in 2030) [1]. This increasing need lead to more
focus on developing more durable implants. Until now, there is no record of successful long-term
implantation of metallic device in human body. In the past, the used materials were silver and gold
which are believed as bioinert materials, but they are expensive and exhibit poor mechanical
properties. After Lister introduced his aseptic surgical technique, the metallic alloys have been
developed to be used in medical implants [2]. The metallic alloys find wider applications in medical
implants than pure metals due to their enhanced mechanical properties and tribological properties

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besides good biocompatibility. The first implant alloy developed for human was “Sherman Vanadium
Steel” [3]. This alloy failed to last for long time due to rapid corrosion in human body.

In 1920’s, the stainless steel alloy (18-8 SS) was introduced which, at this time, considered a superior
corrosion resistant alloy compared to available alloys [4]. After that time, researchers focused on
developing high corrosion materials to be used in medical application. Later, 316L SS, Cobalt alloys
and Titanium alloys introduced and proved high mechanical properties as well as good
biocompatibility. Biocompatibility is a term used to describe the behavior of material dealing with
living tissue, which is non-toxic, not releasing harmful elements and not causing allergic effects [5].

Studies showed that metallic substrates release metal ions which may be considered toxic and

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hazardous. Also, the metals induce poor bioactivity which means that metals do not form chemical
bond with living tissues. By the 1930’s, polymers were used in biomedical applications, but were
limited in load bearing applications for their lower mechanical properties than metals. In 1970, Larry

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Hench introduced bioactive glass [6], Figure 1 shows the development of implants materials in the
last century [7].

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Figure 1: History of implants materials development [7]

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Bioactive materials are active to form chemical bond with human bones. Bioactive material is a
blend of oxides (SiO2, CaO, MgO, P2O5, etc.) which stimulates the composition of bones. Bioactive
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glass, wollastonite, and Hydroxyapatite (HA, Ca5(PO4)3(OH)) are commonly used in implants because
of its excellent bioactivity [8]. Usually the most important elements in bioactive materials are Ca and
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P and the ratio Ca/P should be controlled (Ca/P ratio in bones is 1.67). These bioactive materials
faced limitations in medical applications especially load-bearing implants because they are brittle
and weak [9]. These materials have very low fracture toughness (usually < 1 MPa.m1/2) compared to
cortical bones (2-10 MPa.m1/2) [10]. In the other applications which no load or small loads are
induced, the bioactive materials proved excellent treatment results, as an example the middle ear
bones replacement [11].

Recently, new trend has been developed to combine the superior properties of metals (especially
the excellent fracture toughness) and the properties of bioactive materials (bioactivity and
biocompatibility). Numerous of researches focused on developing techniques for coating or
depositing bioactive materials on metallic substrates to improve the mechanical, tribological and
biomedical properties of biomedical implants. These techniques of improvements are still under

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investigations and further studies are needed to obtain long-term implants. The different coating

Reviewer comment 1
techniques used are still under investigations and further studies are needed to obtain long-term
implants. Further studies on the adhesion strength between coating and substrate, develop
multilayers to provide different characteristics, application of new materials (as metallic glass), and
more focused in-vivo tests on developed techniques.

In this paper, we will focus on the most common metallic alloys used in biomedical implants,
bioactive materials and the techniques developed to improve the performance of the implants.

2. Metallic alloys in biomedical

biomedical implants

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After the discovery of iron, humans used iron in food containers and other usages. Silver and gold
were used in bone implants and dental replacement. In fact, the materials dealing with living tissues
should meet the following requirement; non-toxic, high corrosion resistance, accepted by living

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tissues and have suitable mechanical properties as hardness, UTS, fatigue limit, and Young’s
modulus.

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Generally, there is no total inert metal or in other words doesn’t corrode in the human body. So, the
metals and their alloying elements are evaluated according to their toxicity level and durability in the
human body. As a fact, metals exist in human body for certain functions. Normal concentrations of

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different elements are listed in

Table 1 [2]. These elements when exceed certain levels, they become harmful. The human body is
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highly corrosive media, so as the metals corrode, hazardous metal ions released [12].

Table 1: Metallic elements in human body, their functions and normal concentrations
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METALLIC NORMAL
FUNCTION
ELEMENT CONCENTRATIONS
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Contained in heme groups of hemoglobin and myoglobin which are required for
oxygen transport in the body. Anemia is the primary consequence of iron
FE 4-5 g in body
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deficiency. Excess iron levels can enlarge the liver, may provoke diabetes and
cardiac failure.

Contained in enzymes of the ferroxidase system which regulates iron transport in

the blood and facilitates release from storage. A copper deficiency can result in
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CU 0.9-2.8 µg/L [13]

anemia from reduced ferroxidase function. Excess copper levels cause liver
malfunction and are associated with genetic disorder Wilson’s Disease

Important for reproductive function due to its role in FSH (follicle stimulating
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hormone) and LH (leutinizing hormone). Required for DNA binding of zinc finger
ZN 2 g in body [14]
proteins which regulate a variety of activities. An excess of zinc may cause anemia
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or reduced bone formation.

Major component of the mitochondrial antioxidant enzyme manganese

superoxide dismutase. A manganese deficiency can lead to improper bone
MN 2-4 mg/day in body [15]
formation and reproductive disorders. An excess of manganese can lead to poor
iron absorption

CO Contained in vitamin B12. An excess may cause cardiac failure. 0.3 to 0.9 µg/L [16]

Required for the excretion of nitrogen in uric acid in birds. An excess can cause
MO 0.6-13.1 µg/L [17]
diarrhea and growth reduction.

A cofactor in the regulation of sugar levels. Chromium deficiency may cause

CR hyperglycemia (elevated blood sugar) and glucosuria (glucose in the urine). 0.4-0.6 µg/L [16]
Elevated levels of some forms of chromium, such as Cr(VI), can be carcinogenic

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Usually, the metallic implants failed to prove durability and long-term due to severe bio-corrosion.
Developments and improvements were made to the alloys to increase their corrosion resistance.
The corrosion of implant can be minimized as follows:

1. Usage of appropriate metals.

2. Avoiding implantation of different types of metal in the same region. This may cause electro-
chemical corrosion.
3. Design the implant to minimize notches, pits and crevices.
4. Recognize that metal corrosion resistance is not the same all over the body [3].
In the next sections, we will present the most common metallic alloys used in implants considering

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their properties, applications and limitations of use.

2.1. Stainless steel alloys (SS)

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Stainless steel is iron-based alloy. The alloy contains Cr, Ni, Mo, Mn, Si, Cu, and carbon. Stainless
steel is featured for its high corrosion resistance when first revealed in the early of 20th century. This

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feature is referred to the formation of chromium oxide film which is stable and prevents further
oxidation. In 1930’s, clinicians used 18-8 SS as biomedical implants, but it failed to prove durability
due to rapid corrosion. Further developments were carried out to enhance the corrosion resistance
and new SS alloys were presented.

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2.1.1. 316L Stainless Steel
A further development of 18-8 SS has been done by adding Ni. It is found that the corrosion
resistance is enhanced when Ni is added, and this called 316 SS. After that, it was found that the
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carbon causes the formation of chromium carbides which is located at the grain boundaries leading
to localized corrosion. So, decreasing the carbon content improved the corrosion resistance of the
SS, and 316L SS is introduced [2][3]. Chemical composition of 316L SS are shown in
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Table 2.
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Table 2: Chemical composition of 316L SS, compositions presented are in % wt. [18]

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Material Fe Cr Ni C S P Si
316L SS Balance 16.0-18.0 10.0-14.0 0.03 0.03 0.045 1.0
For long years, 316L SS was considered for medical devices and implants used in trauma surgeries
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[19], Figure 2 shows examples for biomedical implants made from 316L SS in (a) knee replacement
and (b) ankle replacement [2]. 316L is featured for its accepted mechanical and tribological
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properties. The mechanical properties of 316L SS is shown in Table 3. Also, the 316L has high
ductility and can be easily manufactured.

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Figure 2: Examples of 316L SS implant in (a) knee, (b) ankle [2]

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Table 3: Mechanical properties of 316L SS [20]

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Material UTS, MPa Yield strength, MPa Modulus of Elasticity, GPa
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316L SS 1170 480 190

316L SS has reasonably biocompatibility and proved success in implants. Until now, 316L SS is the
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most common used alloy in medical implants due to its low cost, accepted biocompatibility and good
mechanical properties [21]. Moreover, 316L are approved by the US FDA (Food and Drug
Association).
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The studies showed the high risk of releasing of Ni ions in human body which result from the bio-
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corrosion of 316L SS when implanted. For this reason, 316L SS was approved only for short-term and
temporary implants. Ni is important in 316L SS as it stabilizes the austenitic phase (austenitic SS is
preferred rather than martensitic SS in implants) [22].
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Although the proposed high corrosion resistance of 316L SS, they showed poor durability as implant
in human body. Normally, they corrode rapidly when implanted and corrosion failures take place as
shown in Figure 3. So, their applications are limited in medical devices or short-term implants [2][4].
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Also, the release of Ni ions, which included in the 316L SS alloy, may cause severe adverse effect on
the human health. Further development introduced a Ni-free SS alloy with enhanced properties.
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Figure 3: Corrosion failure of SS implant [2]

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2.1.2. Ni-free, high concentration Stainless Steel (ASTM F2229)
New developments were investigated to enhance the biocompatibility of 316L by replacing Ni with
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high concentration of nitrogen. Nitrogen was found to act as austenitic phase stabilizer replacing
hazardous Ni. So, Ni-free, high concentration nitrogen SS (ASTM F2229) was developed (Table 4
shows compositions (in wt.%) of 316L SS and ASTM F2229). The ASTM F2229 SS proved better pitting
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corrosion, wear and corrosion resistance than conventional 316L SS [23]. Besides, it showed
enhanced fatigue strength and hardness [7]. The developed alloy has great potential in biomedical
applications, but still need further studies to evaluate its biomedical properties.
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Table 4: Composition (in wt. %) of 316L SS and Ni-free, high concentration SS (ASTM F2229)
Stainless Steel type Cr Ni Mo Mn Si Cu N C P S
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316L SS (ASTM F138) 17.00-19.00 13.00-15.00 2.25-3.00 2.00 0.75 0.5 0.1 0.03 0.025 0.01
ASTM F2229 19.00-23.00 0.10 21.00-24.00 0.50-1.50 0.75 0.25 >0.90 0.08 0.03 0.01

The developed Ni-free SS has enhanced bio-corrosion (Figure 4), enhanced fatigue resistance, and
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excellent cytocompatibility near to commercial pure titanium, (Figure 5) [7].

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CP Ti

ASTM F2229 SS

316L SS

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Figure 4: Potential/current density curve for 316L SS, ASTM F2229 SS and CP Ti [7]
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CP Ti
316L SS
ASTM F2229 SS
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Figure 5: Cell growth obtained on ASTM F2229 SS, 316L SS and CP Ti [7]

2.1.3. Mechanical and biocompatibility properties of SS

The nature of loads is static and dynamic. The dynamic load is more critical as the most of implants
fail due to lack of fatigue strength. Normally, the implants are directed to corrosion and pitting
corrosion due to the aggressive behavior of the human body which affects the fatigue resistance.

Generally, SS-alloys are reliable in terms of fatigue resistance. However, the alloy showed reduced
fatigue properties (by about 20% of dry fatigue strength) when subjected to corrosive media (Figure
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6) [2]. As a fact, SS is very sensitive to fatigue failure in corroding environment, which increase the
possibility of failure due to fatigue.

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Figure 6: ASTM F2229 SS fatigue performance in air and in 0.9% NaCl solution [2]
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SS has poor pitting and crevice corrosion resistance because of the chromium carbides formed on

Reviewer comment 2
the grain boundaries [23], [24]. So, SS implants failures which were reported because of fatigue
failures, was due to initiation of cracks at very poor surface finish and crevice corrosion sites.
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However, the developed F2229 SS proved better crevice corrosion resistance because of the
addition of nitrogen, but still need more investigations [25]. (Table 5 shows mechanical properties
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of 316L SS and ASTM F2229). Another point is the inferior wear resistant of SS alloy which caused by
debris release and reduce life. So, SS alloy are limited in joint replacement which directed to
relatively wear rates [7].
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Table 5: Mechanical properties of 316L SS and ASTM F2229

Yield strength, Fatigue Fatigue strength Max
Stainless Steel type UTS, MPa Hardness, HRC
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MPa strength in air in PBS elongation, %

316L SS (ASTM F138) 490-1350 190-690 220-600 220-600 25-39 12-40
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ASTM F2229 931-1731 586-1551 650 500 43-50 12-52

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*The fatigue strength is measured at 10 cycles

As a conclusion, SS alloys are featured to be relatively cheap alloy, have suitable biocompatibility,
and exhibit good mechanical properties. In addition, it is widely used and is approved from FDA (US
Food and Drug Administration) as temporary biomedical implant material [26][27].

On the other side, SS alloys have poor bio-corrosion resistance and pitting corrosion resistance,
reduced fatigue performance in corroding media, no bioactivity, and poor wear resistance. Even the
developed ASTM F2229 SS proved better properties (as fatigue, wear and corrosion resistance, no Ni
ion release) to replace the 316L SS, it still lacks to make sufficient bond with bones which may

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experience implant release. Further studies should be held to ensure the bio-performance of this
alloy. Also, higher nitrogen concentrations affect the toughness of alloy [4][7].

2.2. Cobalt alloys

In the early of 20th century, the CoCrMo alloy presented and was employed in aircraft applications.
The alloy includes Co as base metal, Cr, Mo, W, C, and Ni as alloying elements, the role of alloying
elements is listed in Table 6. The alloy showed great corrosion and wear resistance and excellent
mechanical properties (UTS, fatigue strength, Young’s Modulus) even at elevated temperatures. The
alloying elements Cr, Mo, and Ni are responsible for the excellent wear and corrosion resistance [2].

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In 1940s, the alloy found the first application in medical implants in dental application. After that,
the alloy was developed and utilized in orthopedics and joints Figure 7 shows knee replacement
made of CoCr alloy) because of their excellent wear resistance and galvanic properties [19][28].

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Table 6: Roles of various alloying elements in Co-alloys

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Alloying element Rule in Co-alloy
Cr Enhance wear and corrosion resistance
Ni Enhance corrosion resistance, increase strength and castability
Mo Enhance corrosion resistance and increase strength

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C Enhance wear resistance and increase castability
W Enhance strength, but decrease corrosion fatigue strength and corrosion resistance
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Figure 7: knee replacement made from CoCrMo alloy

2.2.1. Biocompatibility of Co-

Co-based alloys
Although Co, Cr, and Ni are classified as high toxic elements [12], the alloy CoCrMo showed high
biocompatibility due to its high corrosion resistance which limits the ion release of toxic elements
[29]. Co-based alloys succeeded in medical implants and considered as permanent implant replacing
SS alloys, besides the superior mechanical properties. Co-based alloys replaced 316L SS in joint
replacement as they exhibit excellent wear resistance. However, in long term the metal-on-metal
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contact results in debris which release cobalt and chromium ions in the human body causing severe
adverse effects [29].

Moreover, CoCrMo alloy showed low osseointegration and exhibited no bioactivity beside the cost,
which is great challenge for Co-based alloys [19]. M. Plecko et al. investigated the osseointegration
of different metals. The results showed poor osseointegration, even lower than stainless steel, which
brings a new limitation for CoCr-alloys. Figure 8 shows the fluorescence and toluidinblue dye of
bone-section after removal of screw implant. The figure shows lower new cells developed at the
interface in the case of CoCr implant (the grey color represent the old bone cells and the blue color
represent the new cells formed) [19]. For this reason, further studies should be held to evaluate the

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toxicity, biocompatibility and osseointegration of the Co-alloys.

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(a)

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(b)

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Figure 8: Bone sections after removing screw implants (a) CoCr alloy, (b) Stainless Steel

2.2.2. Mechanical Properties

Properties of Co-
Co-based alloy
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CoCrMo alloys are widely used in biomedical implants for their high wear resistance and high
hardness. Also, they exhibit high mechanical strength (UTS 960 MPa), Table 7 compares the
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mechanical properties of Co-alloys and ASTM F2229, and high polishing surface quality which
enhance the corrosion resistance and minimize the pitting and crevice corrosion. They have
excellent fatigue resistance behavior (107 cycles at 610 MPa) even when notched, and can be
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improved by post treatments (the fatigue strength is increased by 100% to 120%), Figure 9 shows
superior fatigue behavior of Co-alloys over 316L SS [30]. They showed excellent fatigue resistance
when subjected to corroding media, Figure 10 [2].
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Table 7: Mechanical properties comparison between Co-alloys and ASTM F2229

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Yield strength, Fatigue strength Fatigue strength Max elongation,

Material UTS, MPa Hardness, HRC
MPa in air, MPa in PBS %
Co-alloys 650-1900 450-1610 200-950 100-200 47 12-50
ASTM F2229 931-1731 586-1551 650 500 43-50 12-52

However, Co-alloys has poor fatigue strength in PBS – 100-200 MPa which is marginally unsafe
compared to the loadings for arms and legs which may reach 200 MPa – which result in lower
success rate of Co-alloys implants after 20 years [2].

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Figure 9: fatigue strength of SS and Co-Cr alloys [2]

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Figure 10: Fatigue performance of Co-alloy in air and physiological solution [2]

As a conclusion, the main features of CoCrMo alloy are excellent corrosion resistance, excellent wear
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resistance, superior mechanical properties, and high fatigue resistance in air. These features make
Co-alloy excellent for biomedical applications (it occupies about 20% of the joints replacement - hip
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and knee joints - market). However, Co-alloys have low ductility, poor fatigue in PBS, increased cost,
and need expensive fabrication processes are the main drawbacks. In addition, they are high density
(9.8 gm/cm3) alloys, and may release toxic metal particles. These drawbacks limit the increasing use
of Co-alloys in biomedical implants. One of the other issue facing Co-alloys is the implant failure due
to fretting fatigue. However, CoCrMo alloy is still the most popular alloy used in joints because of the
excellent wear and corrosion resistance [2].

2.3. Titanium alloys

Ti alloys were first introduced as structure material in aerospace application. Later, in 1950 Ti-alloys
were employed as dentistry implants. After that, it became of great interest to be used in bone
implants [7]. Ti is considered non-toxic, even at high doses, to the human body [6], [10], [31].

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Titanium is low density metal (4.8 gm/cm3) which offer superior specific strength over other
common alloys. Pure titanium can be used, but for limited application because of their relatively
insufficient mechanical and fatigue strength, however, studies showed that titanium fatigue
performance does not affected in corroding media [32]. This makes high potential for using titanium
in biomedical applications. To enhance the mechanical properties, the titanium is strengthened by
adding alloying elements as Al, V, Nb, Zr, Mo, etc. [32]. Ti6Al4V is one of the most common alloy
used in biomedical applications for its excellent mechanical properties.

2.3.1. Biocompatibility of Ti-

Ti-alloys

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Ti alloys – especially Ti6Al4V – proved excellent corrosion resistance and biocompatibility. The in
vitro and in vivo tests showed that Ti element is safe for human body and possess high
osseointegration (the formation of a direct interface with bones without intervening soft tissues) ,

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Figure 11 shows the infusion at the interface between host bone and Ti implant.

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Titanium Bone
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implant tissue
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Figure 11: infusion at the interface between bone and Ti implant [2]

It is noted that Ti has excellent biocompatibility and exhibit the highest polarization resistance,
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which resulted on great concern on developing Ti-alloys, Figure 12 shows the biocompatibility of
different metallic element [7]. It is however should be noted that Al and V are reported to have
allergic effect on the human body. So, development of second generation of Ti alloys was proposed
by replacing Al and V with Zr, Ta, and Mo which are considered relatively safe for human body
[7][32]. Alloys Ti6Al7Nb, Ti5Al2.5Fe, Ti15Zr4Nb2Ta, etc. were developed for biomedical applications
as they are allergy-free alloys. However, these alloys contains elements with different specific weight
and melting point causing non-homogeneity of the casting which requires advanced manufacturing
processes [7].

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Figure 12: Biocompatibility and polarization resistance of metals [7]

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2.3.2. Mechanical properties of Ti-
Ti-alloys
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Generally, with low density and strength (500 MPa) comparable to that of 316L SS, the most
featuring property of Ti-alloy is their superior specific strength (288 N.m/kg while 63 N.m/kg for SS)
and have relatively low Young’s Modulus (80 GPa) which is near to the value of cortical bones [2],
[32]. Table 8: Mechanical properties of pure Ti and Ti6Al4V alloy. This reduce the effect of stress
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shielding which may cause the release of implant form the bones. The Ti-alloy proved no change in
fatigue behavior in PBS (Figure 13 shows that the fatigue strength remains the same in air and in
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PBS). However, Ti-alloy is sensitive to fretting fatigue which is about half the plain fatigue strength
[32]. This property causes the fracture of Ti implants, for example, at the neck of THR in Figure 14.
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Table 8: Mechanical properties of pure Ti and Ti6Al4V alloy

Yield strength, Fatigue strength Fatigue strength Max elongation,
Material UTS, MPa Hardness,
MPa in air*, MPa in PBS %
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Pure Ti 241-550 172-480 120-275 100-200 70-100 HRB 15-24

Ti6Al4V 896 827 250-300 250 30-39 HRC 10
* Fatigue life is measured at 107 cycles
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(b)
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(a)

Figure 13: Fretting fatigue and plain fatigue of (a) TiNbTaZr alloy, (b) Ti6Al4V alloy [32]

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Figure 14: Fracture of Ti-implant

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On the other side, titanium is very poor in wear resistance, poor hardness and exhibits low tensile
ductility and low bending strength which made Ti-alloys fail to prove long-term implant especially in
THR (Figure 14 shows fracture of Ti implant due to fretting fatigue) [2]. The implants made of

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titanium should have high surface quality as its fatigue resistance is very sensitive to surface
conditions and the fatigue strength may be reduced up to 40% when notched [2].
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As a conclusion, Ti-alloy is featured for its high specific strength compared to SS and Co-alloys, low
density, high corrosion resistance, and superior biocompatibility and osseointegration. However, Ti-
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alloy drawbacks are their relatively high cost, poor forgeability, high sensitive fatigue strength to
notches and insufficient bending strength, low hardness and low wearing resistance. These
drawbacks limit the application of Ti-alloy in long-term load bearing implants and in joints, however,
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it is highly promising alloy for other biomedical applications [32]. Until now, there is a lack of long-
term application of Ti-alloys in clinical applications due to low wear resistance and inferior both
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fatigue and fretting fatigue strength.

3. Metal based amorphous alloys (Bulk Metallic Glass)

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Recently, amorphous phase alloys or Bulk Metallic Glass (BMG) came to concern because of their
superior mechanical properties and excellent performance in wear and corrosion behavior. BMGs do
not have crystalline structure as conventional solidified metals, Figure 15. BMG was first introduced
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in 1950’s by very high cooling rate (104-107 °C/s) from the vapor or liquid state. At this time the
applications were limited because of limited sizes obtained [33]. Certain studies succeeded to obtain
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amorphous phase at lower cooling rate through using certain levels of alloying elements –
depending on the size of the atoms used – enabling producing much bigger sizes (up to few
centimeters) [34]. Recently, it is proved to obtain amorphous alloys by using different techniques as
ion implantation, electrodeposition or mechanical alloying [35]. Figure 16 shows the development in
BMG systems and the improvements in obtained sizes [36].

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Figure 15: SEM of (a) Zr-based BMG [37], (b) 304 SS [38]

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Figure 16: Historical development in BMG systems and obtained sizes [36]
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The amorphous systems can be categorized as ferrous and non-ferrous alloy systems. The ferrous
alloy system (Fe-Si-B-Nb, Co-Fe-Si-B-Nb, Ni-Si-B-Ta, etc.) are featured for their high magnetic
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properties which can be employed in transformers and other electromagnet equipment. The non-
ferrous alloy systems are employed in different applications like sport, electronics, medical and
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foundry equipment.

Recently, the BMGs have high potential to be applied in biomedical applications. They can be
categorized as biodegradable, like Mg, Ca, and Zn based BMGs, and non-biodegradable BMGs, like
Fe, Ti, and Zr, based BMGs [39]. It was found that BMGs have excellent biocompatibility properties
as high strength, high wear resistance and superior corrosion resistance. Hence, Fe, Ti, Zr based
BMGs are potential candidatures for replacing the crystalline stainless steel, Ti, and Zr alloys.

3.1. Fe-
Fe-based BMG
The Fe-based BMG are considered low, which make it attractive in different applications, besides
their good glass-forming ability. Usually, the developed Fe-based BMG are used in transformers

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cores, inductors, etc. for their good magnetic properties. Considering the biomedical applications,
these magnetic properties are undesirable because it affects the clinical diagnoses using Magnetic
Resonance Investigation (MRI). V. Ponnambalam et al. presented non-ferromagnetic at room
temperature Fe-based BMG which may be applied in biomedical implants [40].

3.1.1. Mechanical properties of Fe-

Fe-based BMG
The Fe-based BMGs exhibited excellent mechanical properties. They have high ultimate tensile
strength, yield strength, and high hardness. X.J Gu et al. evaluated the mechanical properties of non-
ferromagnetic Fe-based BMG. The results revealed that the constitution of the alloy affects its

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strength as well as their elasticity and plasticity [41]. The authors studied 23 different Fe-based BMG
alloys and the results obtained are summarized in Table 9 compared with ASTM F2229 SS and CoCr
alloy. The mechanical properties of Fe-based BMG are outstanding, but it exhibited small elongation

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until fracture and it is limited bulky sizes (up to 16mm in diameter).

Table 9: compares the mechanical properties of Fe-based BMG with ASTM F2229 and CoCr alloy

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Material Yield strength, MPa UTS, MPa Plastic strain, % Vickers Hardness, GPa
Fe-based BMG 3400-3800 3800-4400 0-0.8 8-11
ASTM F2229 SS 586-1551 931-1731 12-52 0.42-0.51

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CoCr 560 960 20 0.47
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An important mechanical property required in biomedical implant is the fatigue strength. Normally,
the crystalline alloys exhibit endurance limit (maximum stress for 107 cycles) about 0.4-0.6 of their
fracture strength. D.C. Qiao et al. studied the fatigue behavior of Fe-based BMG
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(Fe48Cr15Mo14C15B6Er2) and found that its fatigue strength is considerably high (682 MPa), but with
lower endurance limit/tensile strength (4.4 GPa) ratio (0.155). However, the material failed abruptly
when the endurance limit is exceeded. Figure 17 shows the fatigue behavior of Fe-based BMG [42].
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Figure 17: compares the fatigue behavior of Fe-based BMG, Zr-based BMG, High nitrogen steel, and Al-alloy
[42]

3.1.2. Biocompatibility of Fe-

Fe-based BMG

Fe-based BMGs are reported to exhibit enhanced biocompatibility than stainless steel due to its
promising corrosion resistance and mechanical properties, especially in body simulated solutions. In
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addition, the developed non-ferromagnetic Fe-based BMG is nickel free, which results in less
hazardous effect as medical implant. Figure 18 shows the surface morphology of Fe-based BMG and
316L SS before and after immersion in Hank’s solution.

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Figure 18: Surface morphology of (a) Fe-based BMG, (b) 316L SS, (c) Fe-based BMG after immersion in Hank’s
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solution, and (d) 316L SS after 15 days immersion in Hank’s solution [43]
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Y.B. Wang et al. studied the performance of three different Fe-based BMG in body simulated
solution and compared with 316L SS performance. They measured the amount of ion release and
the cell growth on the different substrates. The result showed negligible ion release from the
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different Fe-based BMG compared to 316L SS, Figure 19 [43].

The results showed that better biocorrosion and pitting corrosion resistance of Fe-based BMG than
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316L SS, as well as high cell growth which reveals the biocompatibility potential of Fe-based BMGs.
However, these BMGs needs more in vivo and in vitro investigation before introducing to the
market.

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316L SS
Fe41Co7Cr15Mo14C15B6Y2
(Fe44Cr5Co5Mo13Mn11C16B6)98Y2

Fe48Cr15Mo14C15B6Er2

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Figure 19: Metal ion releasing in Hank’s solution for different Fe-based BMG and 316L SS [43]
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3.2. Ti-
Ti-based BMGs
Titanium and its alloy are of great concern in the recent decades to be utilized in biomedical
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applications due to their excellent corrosion resistance, biocompatibility, and mechanical properties.
However, enhanced mechanical properties are required. BMG systems present better mechanical
properties and corrosion resistance behavior. Late in previous century, Ti-based BMG was presented
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with enhanced mechanical and biomedical properties which can be considered further development
Ti-alloys for permeant implants.
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3.2.1. Mechanical properties of Ti-

Ti-based BMGs
Many researches were held to evaluate different Ti-based BMG alloys. The presented Ti-based BMG
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has relatively low Young’s modulus (80-120 GPa), higher tensile strength (1700-2500 MPa), and
enhanced corrosion resistance, Table 10 [39]. As mentioned before, fatigue strength is very
important factor for biomedical implants. It is reported that Ti-based BMGs have promising fatigue
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strength reaching 1.5 GPa and the ratio of endurance limit to tensile strength is high up to 0.8. This
indicates that Ti-based BMG may not undergo fatigue phenomena, Figure 20 shows the S-N curve of
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different BMG alloys and crystalline alloys [44].

Table 10: Mechanical properties of Ti-based BMG and Ti6Al4V

Material Fatigue Strength, Young’s Modulus, Elongation,
UTS, MPa Vickers Hardness, GPa
MPa* GPa %
Ti-based BMG 1700-2500 1500 68-102 2.3 4-5
Ti6Al4V 896 250 80 10 0.30-0-39
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*The fatigue strength is evaluated at 10 cycles

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No. of cycles

Figure 20: S-N curve of different BMG systems[44]

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3.2.2. Biocompatibility of Ti-

Ti-based BMGs
Many studies investigated the corrosion behavior of Ti-based BMGs in different types of body
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simulated solutions, like phosphate-buffered solution (PBS), Hank’s solution and Ringer’s solution.
The studies showed higher corrosion resistance than crystalline Ti-alloys. Ling Bai et al. investigated
in vitro behavior of Ti70Zr6Fe7Si17 and Ti64Zr5Fe6Si17Mo6Nb2 (at.%) BMG alloys. The results showed
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excellent biocompatibility of both alloys, moreover, the morphology of the specimen revealed
forming HA after 15 days of immersion in SBF, Figure 21 [45].

These results reveal the promising potential of using Ti-based BMG in biomedical implants replacing
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the crystalline Ti-alloys. However, Ti-based BMG is limited in size (up to 15mm in diameter) and
needs further investigation for both in vitro and in vivo behavior.
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Figure 21: SEM image of Ti-based BMG showing formation of HA after 15 days cultivation in SBF [45]
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3.3. Zr-
Zr-based BMGs
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The Zr-based BMG has high potential since introduced in 1993 by Peker and Johnson [46] due to
their promising mechanical properties and biocompatibility (see Figure 12) [47]. Zr-based BMG has
high tensile strength, low Young’s modulus, good toughness and good corrosion resistance which in
turn become promising in biomedical implants [47].
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3.3.1. Mechanical Properties of Zr-

Zr-based BMG alloys
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Zr-based BMG showed relatively high tensile strength (up to 2 GPa), relatively low Young’s modulus
(about 90 GPa) [48]. In addition, it exhibits good wear resistance, high hardness and high specific
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strength [37]. It showed to have the same hardness of GCr15 (HRC 60-63), but has higher
compressive strength (1900 MPa) and higher fracture toughness (55-59 MPa) [46], Table 11:
Mechanical properties of Zr-based BMG compared to Ti6Al4V.

Another important property is the fatigue strength. Certain studies revealed that Zr-based BMG
alloys has fatigue limit which is low as 6-8% of the tensile strength (120-160 MPa) compared to
conventional crystalline steel and aluminum alloys [49]. G.Y. Wang et al investigated the fatigue
behavior of three different Zr-based BMG alloys. The results revealed promising Zr-based BMG has
fatigue limits comparable with high-strength crystalline alloys, Figure 22 shows (a) the fatigue
behavior and (b) fatigue limits versus tensile strength of different BMG and crystalline alloys [50].

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Table 11: Mechanical properties of Zr-based BMG compared to Ti6Al4V
Material UTS, MPa Fatigue Strength, MPa* Young’s Modulus, GPa Hardness, HRC
Zr-based BMG 2000 550 90 55-59
Ti6Al4V 896 250 80 30-39
*Fatigue is evaluated at 107 cycles

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Figure 22: (a) Stress-Life curve of three different Zr-based BMG alloys in vacuum and in air, (b) Fatigue limit vs
yield strength of BMG and Crystalline alloys [50]
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3.3.2. Biocompatibility of Zr-
Zr-based BMG
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One of the key properties for biocompatible materials is the corrosion resistance. Many studies
investigated the corrosion resistance of Zr-based BMG in various physiological solutions. The results
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showed enhanced corrosion resistance than conventional crystalline alloys - like stainless steel, Co-
alloys and Ti-alloys [39]. This because of the passive film formed which is composed of ZrO2. It was
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revealed that the addition of Yttria 1% wt. enhanced the biocorrosion resistance of Zr-based BMG
alloy [51].

Other studies investigated the biocompatibility of Zr-based BMG both in vitro and in vivo. The
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findings showed superior biocompatibility of Zr-based BMG over crystalline stainless steel, Zr-alloys
and Ti-alloys [39]. Yu Sun et al investigated the in vitro and in vivo biocompatibility of Ag-bearing Zr-
based BMG and compared with pure Ti and Ti6Al4V. Figure 23 shows the developed pits on the
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surface of the specimen. It is cleared that pure Ti and Ti6Al4V alloy exhibited larger pits than that in
Zr-based BMG [52].
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Figure 23: SEM image of (a) Zr51.9Cu23.3Ni10.5Al14.3, (b) Zr51Ti5Ni10Cu25Al9, (c) pure Ti, (d) Ti6Al4V after 15
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day of immersion in Hank’s solution at 37 C [52]
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Generally, Zr-based BMG alloys are promising materials for biomedical applications because of their
excellent mechanical and biocompatibility properties. However, Zr-based BMG alloys products are
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limited in size, as well as, they are very brittle in tension and show less plasticity in compression [53].
Although the fracture strain can be improved from 2% to 5.5% regarding to the existence of
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crystalline phase within the amorphous matrix, it is still need more investigation [54]. In addition,
the production processes are expensive as it requires high purity elements and expensive
consumables [36]
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4. Bioceramics
Bioceramics are referred to materials that are biocompatible. The bioceramics are bioinert,
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biodegradable, or bioactive. The bioinert ceramics are non-toxic and does not interact with the living
tissues. The biodegradable ceramics allow the living tissue to replace the implant, i.e. the
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biodegradable ceramic is resorbed in the human body. Another promising bioceramics are bioactive
materials as Bioglass and hydroxyapatite which are able to form bond with hard and soft tissues
[55]. The bioceramics are of strong potential to be used in scaffolds and bone grafts to treat
fractured and damaged bones because of their high biocompatibility, low cytotoxicity and high
corrosion resistance [56][57]. However, the bioceramics are brittle due to their oxide nature which
limits their application in load-bearing implants.

4.1. Bioinert and biodegradable ceramics

The bioinert ceramics have great potential in biomedical applications because of their high corrosion
and wear resistance, and non-toxicity behavior. The bioinert ceramics result in fibrous tissues
formation at the implant interface.
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Zirconia (ZrO2), alumina (Al2O3), Tantalum oxide and other metal oxides are examples of bioinert

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ceramics. Alumina is the most common used bioceramics for their excellent tribological and
biocompatibility behavior, in addition, their high mechanical properties [55]. The alumina has
successfully utilized in knee and hip joints prosthesis [58].

Furthermore B. Rahmati et al showed that Tantalum oxide (Figure 24) has excellent biocorrosion and
wear resistance (Figure 25 shows worn (a)Ti6Al4V and (b) Tantalum oxide surfaces) besides the
mechanical properties. The Tantalum oxide is featured for low ion release, high hardness, and
excellent wettability [57], [59].

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Figure 24: SEM image of Tantalum oxide [60]

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Figure 25: Worn surface of (a) Ti6Al4V, (b) Tantalum oxide [57]

On the other hand, Zirconia (ZrO2) has superior mechanical properties exceeding alumina (Table 12
compares the properties of alumina, zirconia and TaO) and excellent biocompatibility properties
[55]. Usually, zirconia is doped with Y2O3 (Yttria Stabilized Zirconia YSZ) to enhance the properties -
YSZ has low thermal conductivity and high thermal stability - and improve the microstructure, Figure
26 [61], [62]. ZrO2 is used to increase stability and hardness of HA [63].

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Table 12: Physical and mechanical properties of alumina and zirconia
Property Alumina (Al2O3) Zirconia (ZrO2) Tantalum Oxide
Density, (g/cm3) 3.90 – 3.93 5.60 – 6.12 8.2
Surface roughness, Ra (µm) 0.02 0.008 -
Hardness, (HV) 2000 - 2300 1300 450-535
Bending strength, (MPa) 400 – 550 1200 -
Young’s modulus, (GPa) 380 200 100
Fracture toughness, K1c (MPa.m-1/2) 5-6 15 3-10 [64]

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Figure 26: SEM of sintered (a) ZrO2 [61], (b) YSZ [62]
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The biodegradable ceramics are resorbed in the human body. These materials are degraded and
then replaced by the living tissue which is highly considered to treat broken bones. Mainly,
biodegradable ceramics are certain phases of calcium phosphates which is the main constitute of
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bone. The ratio Ca/P controls the solubility of calcium-phosphate phases. The β-tri-calcium
phosphate, tetra-calcium phosphate, and CaO are the common biodegradable phases. When the
surface of calcium-phosphate is directed to water and certain level of temperature, it forms
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bioactive phase (hydroxyapatite) [55]. These biodegradable are not stable at high temperatures
which limits fabricating them into biomedical implants [65].
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4.2. Bioactive materials

For medical implants, it was thought that the best material is the most inert until 1969 when L.
Hench and his research team introduced bioactive glass. Bioactive glass can form chemical bond with
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human bones, Figure 27 shows the mechanism of the bonding between bioactive material and bone
and formation of new bone layers [56], Figure 28 shows SEM image of cell growth on pure Ti and tri-
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calcium phosphate as bioactive material [66]. The number of cells over tri-calcium phosphate is
higher than that on pure Ti surface. This means higher osseointegration and bioactivity of tri-calcium
phosphate compounds. These materials are composed of soda-calcia-phospho-silicate glasses known
as 45S5 Bioglass. Bioactive glass is non-cytotoxic and has the ability to form hydroxyapatite (HA)
layer on its surface equivalent to the composition of living bones [67]. For this reason, wide clinical
applications used bioactive glass in dental and bone treatment. Bioactive glasses are reported as
safe for humans and proved no toxicity to the living tissues [68].

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Figure 27: Formation of new bone layer on HA surface [56]; (1, 2) Solubility of HA in physiological fluid, (3)
equilibrium betweeen the HA phase and physiological fluid, (4) adsorbtion of proteins and other bio-organic
compounds, (5, 6) Cell adhesion and growth, (7, 8) formation of new bone

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Figure 28: SEM image of cell growth after 11 days of cell-culture on (a) pure Ti, (b) Tri-calcium phosphates [66]
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Other materials showed bioactivity behavior like synthesized hydroxyapatite (HA), bioactive
ceramics based on borate and borosilicate, and natural wollastonite (Ca-SiO2) [69], [70], [71].
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Scaffolds – an artificial structure that provides support for growing tissues and cells [72], Figure 29
[73] – should be 3D-porous to increase the surface reactivity in physiological fluids and
consequently, enhance the bond strength with living tissue. Beside the chemical composition, the
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microstructure and morphology of the bioactive scaffold affects the performance [73]. In this paper,
we will focus on bioactive glass and hydroxyapatite as the most common used bioactive materials.
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4.2.1. Hydroxyapatite (HA)

HA is a popular bioactive material used to treat damaged or defected bones. It is non-toxic and
promote bone growth which lead to enhanced fixation of implants [22]. The main constitutes of HA
is Ca and P, and the common chemical form is [Ca10(PO4)6(OH)2]. This chemical form is near to the
bone which contains Ca, P and water [22]. HA can be natural or synthesized. For pure synthesized HA
– which is most common as it is cheaper and most available, the Ca/P ratio is made 1.67 (Ca/P ratio
in bones is 1.65), which facilitates growth of the living bone [74].

The HA has the advantage to be biocompatible with soft tissues – as skin, muscle, and gum - as well
as hard tissues. This feature brings HA applicable in different biomedical applications. HA degrades

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slowly in vivo, so HA can act as temporary substrate for further development and growth of cells
[75].

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Figure 29: (a) Scaffold specimen made from Bioglass, (b) application of scaffold to repair broken bone [73]

An important factor for successful HA scaffold or implants is the degree of porosity. The porosity

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increases the surface area of porous parts. The cells and bone tissues are grown more on porous
parts which guarantee better bonding and fixation, Figure 30 shows the porosity level in scaffolds in
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different parts of the body [56].
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Figure 30: Different application of bioactive material in body with the corresponding porosity level [56]

Another important factor that affect the resorption of HA is the degree of crystallinity of the
bioactive material interfaced with the living tissues. The dissolution of bioactive material depends on
the degree of crystallinity. The higher degree of crystallinity reduces the resorption rate of the
bioactive material and offer longer life, which is desirable in certain cases [66]. S. Overgaard et al.

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investigated the influence of crystallinity of HA on the bonding strength with bones. They found that
after 16 week low crystallinity of HA (50% crystallinity) exhibited stronger bonding with bone than
high level (75% crystallinity). After 32 weeks, both crystallinity have the same bonding strength with
bones - the bonding of 75% crystallinity HA increased and 50% remains the same. However, the low
crystallinity induced higher degree of cell growth, Figure 31 shows the bone growth on 50% and 75%
crystallinity HA [76]. The arrow shows the HA layer at the interface indicating that higher bone
growth was on 50% crystallinity.

(a) (b)

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100µm 100µm
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Figure 31: Photomicrograph of bone growth on (a) 50% crystallinity HA, (b) 75% crystallinity HA [76] *B=bone,
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BM=Bone marrow
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One of the challenges that faces HA utilization in load-bearing (as hip bone, knee joint) implants is
their brittleness and poor mechanical properties, as strength, fatigue and fracture toughness, Table
13 shows the lack in mechanical properties of HA compared to cortical bone [77]. Another
application challenge is that the different techniques used to fabricate HA implants impose high
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temperatures, which in turn, result in decomposition of HA and form unstable phases. Consequently,
researchers studied doping HA with stabilizing oxides as Y2O3, ZrO2, alumina, SiO2, etc [56]. C. S.
Chien et al studied Flourapatite as substitute of HA. The presented FA showed better stability and
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same bioactivity as HA [10]. Hongjian Zhou et al revealed that nanoscale HA proved better
biocompatibility, enhanced mechanical properties, and osseointegration properties [75].
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Table 13: Mechanical properties of HA and bone [78]

Material Young’s modulus, GPa UTS, MPa Fracture Toughness MPa.m1/2
HA 80-120 40 0.6-1
Cortical bone 1-20 50-150 10-12

4.2.2. Bioactive glass

Bioactive glass (Bioglass) was first presented in 1970’s by L. Hench. Bioglass is compounds of SiO2,
CaO, MgO, Na2O, K2O, and P2O5 [79], Figure 32 presents SEM image of Bioglass particles [80]. The
most common type is bioactive glass 45S5 which consists of 45% SiO2, 24.5% CaO, 24.5 Na2O, and 6%
P2O5 [81]. Bioglass 45S5 is preferred as it showed high rate of bone formation on the surface (just
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one week after implantation) than that for synthetic HA or other calcium-phosphate ceramics, Figure
33 compares the cell growth on different bioactive materials [67].

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Figure 32: SEM of Bioglass particles [80]
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Figure 33: Cell growth rate on different bioactive materials [67]

Normally, Bioglass forms carbonated-HA when interfaced with living cells or tissues. This layer builds
firm bond with bone, Figure 34 shows the formation of bone cells on Bioglass (1) Bioglass particles,
(2) transition layer between Bioglass and bone (3) new bone cells formed [67], which makes Bioglass
promising in biomedical applications. An important issue in fabrication Bioglass is to maintain its
glass-phase rather than crystallization, which in turn makes it difficult to fabricate Bioglass by
sintering [71].

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Figure 34: SEM image showing bone formation around Bioglass particles [67]

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In the other hand, the application of Bioglass – which is considered ceramics – is limited in load-
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bearing implants due to its brittleness and lack of mechanical properties (bending strength and
fatigue), Table 14 compares mechanical properties of Bioglass with cortical bone [75]. Successful
bioactive implants were reported. The first successful clinical use of bioactive glass was in 1985 to
treat damaged middle ear bones. The clinical studies showed better performance than other bio-
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ceramics used. These findings bring the potential use of bioactive glass in bones treatment [67].
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Table 14: Mechanical properties of Bioglass 45S5 compared to cortical bones [68]
Material Young’s modulus, GPa UTS, MPa Fracture Toughness, MPa.m1/2
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Bioglass 45S5 35 42 0.7-1.1

Cortical bone 1-20 50-150 10-12

As a conclusion, bioceramics are of high concern because of their excellent biocompatibility, non-
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toxicity, wear and corrosion resistance. Also, bioactivity – which is offered by Bioglass and HA – is a
promising behavior that improve the performance of implants and enhance fixation. However, these
materials are poor in ductility, fatigue and fracture toughness which limits their usage in load-
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bearing implants. Form the experience of the authors, synthetic HA nano-powder is cheaper than
45S5 Bioglass, nevertheless, 45S5 Bioglass exhibit better cell growth and higher stability during
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fabrication as stated above.

5. Techniques to improve the performance of biomedical implants

Numerous researches focused on improving the performance and durability (nowadays an average
10-15 years lifetime) of biomedical implants [37]. In case of metals, the poor bioactivity and the
release of toxic ions in the human body are the main challenges facing metallic implants. The poor
bioactivity result in poor fixation of implant with the bones which may need revision surgery. Also,
the rapid bio-corrosion of metals cause release of toxic elements that has severe adverse effect on
the health [59][78]. To overcome this problem, surface treatment techniques are used to improve
the chemical, mechanical and biological properties of the surface interfaced with the living tissues.

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The surface treatment is of two main categories; altering the chemical and microstructure of the
surface, or applying coating material on the surface.

The first category includes techniques to modify the chemical composition of the surface – as
carbonization of steels – or modify the surface microstructure, or applying both. These modifications
affect the wettability, surface charge, and hydrophobicity. These properties showed effect on
organic adsorption into the implant surface. Generally, increasing the hydrophobicity of the surface
result in better biocompatibility [82].

S. Muley et al. evaluated the biological performance of 316L stainless steel by developing ultra-fine
grains at the surface. By decreasing the grain size – form 30µm to 0.86µm – the hardness was almost

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doubled (from 172 VHN to 300 VHN), the wear and pitting corrosion resistance increased, and
improved localized corrosion resistance [23]. X. Zhao et al. introduced surface nanotopographic with
chemical modification. The author developed nanotopographic layer of TiO2 doped with Nb2O3 on

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CP-Ti. They realized enhancement in corrosion resistance, bonding strength and biocompatibility
[83].

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Other approaches include developing composite materials (metal-ceramic-matrix) as 45S5 Bioglass-
316L fiber composite. This approach depends on developing scaffolds using bioceramics and
reinforced with 316L fibers to improve the bending strength, fatigue strength, and fracture

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toughness [77].

The second category is coating techniques. Coating techniques have become promising due to the
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combination of the superior properties of both metals and bioactive materials. The bioactive coating
enhances the implant fixation and results in reduced mechanical failure (for fully HA coated implants
the mechanical failure ranges from 1% to 6.9% which is much lower than cement type fixation) [1],
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prevent further ion-release form the metallic substrate, and prevent formation of fibrous tissue
which may result from micro-movements of uncoated implant. Wide range of coating techniques
introduced, but till now an optimal technique has not been developed yet [84]. The researchers
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presented vast coating techniques as physical vapor deposition (PVD), plasma spray, laser cladding
and solution based methods as sol-gel and electrochemical deposition. However, plasma spraying
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still the only approved method by US-FDA for applying bioactive coatings in biomedical application
[63].

A high quality coating should exhibit sufficient adhesion strength (50 MPa approved by US-FDA) [63],
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high hardness of final coat, excellent osseointegration and osseoconduction properties, reduced
cracks among the coating, and free of inclusions. Another important feature is the degree of
crystallinity which affect the solubility of the bioactive coating in the human body [63]. Recently, the
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research work is directed towards developing thin and uniform bioactive coatings to reduce the
fragments and debris produced [85]. In this paper, we will focus on the coating techniques used to
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improve the performance of biomedical implants.

5.1. Physical Vapor Deposition (PVD)

PVD)
PVD techniques are based on vaporizing materials from the source material – called target – to be
deposited on the substrate. PVD is divided into three categories; vacuum, ion spraying and
magnetron sputtering [86]. A vacuumed chamber incubates charged substrate and target with
positive and negative charge, respectively using DC-power supply. Then the process utilizes gas
plasma (argon, neon) which is ionized by means of electric charges. The sputtered ions hit the target
causing evaporation, and free-atoms are ejected from the surface which is deposited on the
substrate. Usually, magnets are used to accelerate the formation of coatings [86]. Figure 35 shows

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PVD magnetron-sputtering setup layout. It is revealed that the substrate temperature affects the
quality of produced coating [59].

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Figure 35: PVD magnetron-sputtering setup [59]

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Numerous researches utilized PVD to coat Ti-alloy with bioceramics to enhance the biocompatibility.
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PVD is featured as versatile technique, developing high purity and dense coatings, Figure 36 show
dense TaO coating developed by PVD. Also, it exhibits excellent adhesion strength with the
substrate, and can deposit any material (metal, alloy, or compound) on the desired substrate [87].
Another important advantage that PVD operates at relatively low temperatures which leads to lower
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degradation of the coating and substrate [88]. B. Rahmati et al. investigated the post heat treatment
to enhance the adhesion strength of previously developed Tantalum oxide coating on Ti6Al4V using
PVD magnetron-sputtering technique. They concluded that higher treatment temperature (500 °C)
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enhance the adhesion strength because of better penetration of Tantalum oxide into the substrate
[60]. So, this technique can deposit bioceramics on metallic substrates.
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WU Zhen-jun et al. presented biocomposite coating (HA/Al2O3) on cp-Ti. The authors employed PVD
to deposit Al on Ti, followed by anodization process to develop Al2O3, and finally using
electrodiposition to deposit HA coating. The results revealed that enhanced adhesion strength
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obtained (21.3 MPa), and improved biocompatibility [89]. Jeong et al. prepared HA coating on
nanotubular TiTaHf alloy, Figure 37 shows the morphology of nanotubular array developed, using
PVD. The authors presented great potential for HA deposited on nanotubular surface as it will induce
better bioactivity and cell adhesion. This may result from the nano-features of the coating on the
surface, Figure 38 shows the nano-feature of HA layer in favor of nanotubular array previously
developed on the surface [90]. E. Mohseni et al. utilized PVD technique to develop multilayer coating
(Ti/TiN/HA) on Ti6Al4V. They studied the process parameters on the adhesion strength, coefficient
of friction, and surface roughness. The results showed enhanced adhesion strength by 44.57% and
surface roughness by 10.52% [91].
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Figure 36: TaO coating layer developed on Ti6Al4V developed by PVD [60]

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Figure 37: Nanotubular array on TiTaHf alloy [90]

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Figure 38: HA coating on nanotubular TiTaHf alloy [90]

PVD is successful to develop bioactive coatings on metallic substrate. Although PVD produces high
dense, high purity and excellent adhesion strength, PVD technique exhibits disadvantages as
expensive and time consuming process, and low crystalline coating which leads to rapid dissolution
of HA coating in the human body [63]. Further studies needed to investigate the effect of PVD
parameters on the porosity and crystallinity of developed bioactive coatings.

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Brohede, U. et al. used PVD technique to develop gradient crystalline TiO2 coating on pure Ti
substrate, Figure 39 shows the developed coating. They evaluated the in-vitro bioactivity of the
developed and found that HA layer was formed on the crystalline TiO2 coating after immersion in
PBS for one week at 40 oC, Figure 40 shows formed HA layer on TiO2. The scratch test showed that
adhesion strength between the coating and the substrate was greater than 1 GPa [92].

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Figure 39: TEM image of the TiO2 coating on pure Ti [92]

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Figure 40: Formed HA layer on TiO2 after one week immersion at 40 C [92]

Many researches focused on PVD to deposit HA on metallic substrate. However, to the extent
knowledge of the authors, no work was published concerning the deposition of Bioglass on metallic
substrate, which represent research gap in this area.

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5.2. Sol-
Sol-gel technique
The sol-gel technique is based on mixing different organic precursors (that contains SiO2, CaO, P2O5)
in aqueous medium to prepare the “sol”, then the mixture is polycondensated to form “gel” which
can be further used for coating. The gel is deposited on the substrate and subjected to sintering to
form the final coating layer [93]. The sintering temperature is considerably low (about 500 °C) which
is lower than other techniques used [63].

Sol-gel technique is simple technique which able to coat complex geometry because of the gel state,
produce high purity and homogeneity coating, and provide excellent adhesion, as well as, good
corrosion resistance coating [94]. This technique can be used to coat metallic substrates with

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bioactive materials.

5.2.1. Hydroxyapatite
Hydroxyapatite coating

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Hydroxyapatite is sensitive to the high temperature and may decomposes, so sol-gel technique is
considered suitable for processing and depositing HA as the sintering temperature is relatively low.

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Number of research works employed sol-gel technique for coating Ti-substrate with thin layer of HA
[95] or functional graded material (FGM) to improve the biocompatibility [96].

A. Stoch et al. deposited HA on Ti6Al4V using sol-gel technique. The authors added animal gelatin to

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the sol to enhance the formation of amorphous phase of HA and studied the pH effect of sol on the
final coating. The result showed the most favorable pH was 6.5-7.8 and the gelatin improved the
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stability of sol. The developed HA coatings showed excellent in-vitro bioactivity which reflects the
success of the proposed technique, Figure 41 shows the resulted morphology after immersion in PBS
for 19 days [97].
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Figure 41: SEM morphology of sol-gel HA coating after immersion in PBS for 19 days [97]

P. Choudhury et al. proposed pure HA and composite HA and ZrO2 coatings on Ti by sol-gel. They
concluded that pre-passivation of Ti substrate increase the roughness which in turn enhance the
bonding strength of the coating. In addition, the composite coating of HA and ZrO2 exhibited higher
bonding strength. However, the coatings are found to be worn by abrasion and delamination [98].

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Not many researches focused on coating SS alloys with HA using sol-gel technique. Dean-Mo Liu et
al. investigated different sintering temperature levels effect on the coating properties of SS. The
results showed that at temperature greater than 400 oC produce better crystallinity, higher bonding
strength (up to 44 MPa), and nano pores, Figure 42. However, the developed coating exhibited
surface micro-cracks and non-uniform thickness [99].

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Nano-pores

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Figure 42: Nano pores at the surface of HA layer [99]

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5.2.2. Bioglass coating

There is few researches considered Bioglass coatings using sol-gel techniques. S. Pourhashem and A.

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Afshar prepared 45S5 Bioglass coating on 316L SS by sol-gel technique. The obtained coatings were
crack-free, Figure 43, have good crystalline structure and exhibited improved corrosion resistance.
The results showed bioactivity behavior and HA formation was realized on the surface [100]. N.
Shankhwar et al. developed new magnetic Bioglass by adding iron oxide using sol-gel technique. The
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developed magnetite glass showed enhanced magnetic properties and in-vitro behavior [101].
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The sol-gel technique is featured as simple coating technique. Also, it is suitable for complex shapes
as the gel-nature can fill gaps, exhibits relatively low sintering temperature, and produce thin layers
of coating. In the other hand, sol-gel has limitations as cracking, low wear resistance, and high
permeability. The sol-gel technique is sensitive to the substrate material as the difference in thermal
properties between the coating and the substrate which cause delamination of coating and hence,
process failure [94]. Hence, further research is needed to overcome major drawbacks as poor
adhesion strength, cracking, and low degree of crystallinity.

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Figure 43: SEM of Bioglass coating on 316L SS

5.3. Plasma spraying

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Plasma spraying is the most common method deployed for coating Ti with HA and the only approved
– by US FDA – technique for biomedical application. The process involves melting material powder
using high temperature plasma gas (up to 15000 °C). The molten powder is sprayed over the surface
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and the coating is developed. Figure 44 shows the principle of plasma spraying technique [63].
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Figure 44: Plasma spray method [63]

Plasm spraying is low cost technique and has rapid deposition rate as well as reduced thermal
degradation than other thermal techniques. However, plasma spraying still lacks to offer high
adhesion strength, cracks [102] and may induce microstructure changes in the developed coating
[63].

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5.3.1. Hydroxyapatite coating
Recently, many researchers focused on coating metallic substrate with HA using Plasma spraying
technique as it is approved by FDA. Kulpetchdara et al. employed plasma thermal spraying in coating
SS substrate with nanostructured HA for hip joint implant. The authors used commercial and
synthesized nano-sized HA, and compared the resulting microstructure (Figure 45), hardness and
bioactivity. The nanostructured HA exhibits higher hardness (VHN 2.15 GPa compared to VHN 1.06
GPa for commercial HA), higher degree of crystallinity, and excellent osseoconductive which can
replace the conventional HA in prosthetic applications [103].

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Figure 45: SEM of plasma sprayed (a) commercial HA coating, (b) synthesized nano-sized HA coating [103]
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The bonding strength of plasma sprayed HA coating with Ti6Al4V is a weak point. M.J. Filiaggi et al.
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proposed post heat treatment of plasma sprayed HA coatings. The results showed dramatically
increase in mechanical properties – bonding strength up to 40 MPa and fracture toughness reaching
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3 MPa.m1/2. However, the chemical composition of the coating was changed which affected the
bioactivity of HA coating [104].
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Manoj Mittal et al. investigated the corrosion behavior of HA coated 316L SS and Ti, and compared
the results with the uncoated ones. The authors used plasma spray to deposit HA on SS and Ti
substrate. The results showed that certain decomposition of HA took place, as well as micro-cracks
on the surface, and porosities, Figure 46 shows the induced micro-cracks and porosities in HA
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coating on SS and Ti. The electrochemical test showed enhanced corrosion resistance of coated
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samples. In addition, the HA coated Ti showed better results than HA coated 316L SS which reveal
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the effect of the substrate material [105]. Y. Wang et al. studied HA coatings on Ti using micro-
plasma spraying. The results showed improved crystallography and higher crystallinity than
atmospheric plasma spraying. The in-vitro tests showed higher HA stability in Hank’s solution for 14
day [106]. V. Shamray et al. proposed preheated substrate to promote the HA coating using plasma
spray. The authors noticed that the composition and structure of the final coating has been affected.
The surface of coating appears to have flattened splats which is formed from molten particles as
shown in Figure 47 [107].

Generally, plasma spraying is an effective technique for depositing HA on metallic substrate, but
exhibit poor crystallinity reduce the lifetime of the coated implants which needs further
investigations and improvements [102].

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Figure 46: Micro-cracks and porosities included in HA coating on (a) 316L SS, (b) Ti [105]

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Figure 47: SEM of HA coating on preheated Ti to 300 C

5.3.2. Bioglass coating

Although the studies reported excellent biocompatibility and bioactivity behavior of Bioglass, few
researches considered Bioglass coating using plasma spraying technique. This is because of the poor
adhesion of Bioglass to the substrate. This can be solved by increasing the surface roughness of the
substrate, developing Bioglass/metallic composite, introduce interlayer as bond coat and in situ
plasma spraying. The in-situ plasma spraying involves preparing suspension containing the raw
materials of Bioglass which is dry sprayed, pressed and sintered. The sintered material is milled to

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obtain the powder. However, these techniques need more investigation to validate the bioactivity of
the resulting coatings [108].

L. Altomare et al. used high velocity suspension flame spraying to deposit Bioglass – dispersed in
aqueous-isopropanol mixture - on grade Ti. The authors deposited multilayer of Bioglass to obtain
denser and thicker layers. The results showed full-glassy structure of the coating and excellent in
vitro bioactivity behavior, Figure 48 shows formed apatite on crystalline Bioglass coating [109].

In another approach, G. Goller et al. utilized 60Al2O3 40TiO2 as interlayer in plasma spraying Bioglass
on Ti, Figure 49 shows the interlayer and Bioglass layer deposited on Ti-substrate. The resulting bond
strength increased three-times (on average 27.18 MPa) compared to the bonding strength obtained

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without interlayer (on average 8.56 MPa). The tests revealed no reaction took place at the interface
[110].

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Figure 48: Apatite formation on Bioglass surface after immersion in SBF for 1 week [109]
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Figure 49: SEM image of the coating layers on Ti (A) Ti-substrate, (B) 60Al2O3 40TiO2 interlayer, (C) Bioglass
layer [110]

5.4. Laser cladding technology (LCT)

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Laser is a promising technique in various applications. Recently, laser was successfully employed in
welding dissimilar materials [38], surface melting and treatment [111], metal additive manufacturing
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[112] and prototyping [113], and coating processes [114]. Laser techniques found wide applications
in different industries; aerospace, marine, oil and gas, and biomedical applications.
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Laser cladding technique was developed to deposit coating material on substrate using laser energy.
The coating material is usually in powder form which may be preplaced [115] over the substrate
surface or injected under pressure [65] or gravity [116]. Laser beam melts the powder – the process
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involves rapid heating and cooling – and creates melt pool without melting the substrate. As the
laser scans the surface, the pool solidifies building a firm and dense coating on the surface. Figure 50
illustrates methods used in laser cladding.
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(a) (b) (c)

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Laser beam
Scan direction

Figure 50: Laser cladding process using (a) by gravity [117], (b) injected powder [118], (c) preplaced powder
[119]

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Laser cladding (LCT) is a promising technique because it produces full-dense coatings with
outstanding properties [120], forms strong metallurgical bond between substrate and coating [121],
able to deposit ceramics or metals on metallic substrate [122], and leads to reduced heat affected
zone (HAZ), Figure 51 shows different zone induced at cladding area [119]. Also, it provides
controlled shape of the coating, flexible process, controlled degree of dilution, low surface
roughness with high deposition rate, and requires minimum surface preparations [123].

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Figure 51: Cross-section of single laser cladded bead showing substrate, HAZ, and cladded bead [119]
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LCT offers metallurgical bonding between coating and substrate, as well as, excellent full-dense
coating layer. Different works investigated coating Ti-alloys and SS – as the most common alloys
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used in implants – with different bioactive materials as HA and Bioglass to enhance the corrosion
resistance, besides the bioactivity behavior.
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5.4.1. Hydroxyapatite coating

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Many studies done to enhance the microstructure of the coating and improve the bonding strength.
These improvements were attained by developing functionally graded carbon nano-tubes (CNT) with
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HA composite coating. The coating consisted of three layers: bottom layer (5% CNT), intermediate
layer (3% CNT), and top layer (pure HA), Figure 52 shows the coating layers and it is noted no
existence of separation between layers. X. Pei et al. found that CNT increased the crystallinity of HA
coating and bonding strength from 14.6 to 29 MPa, besides the excellent bioactivity as shown in
Figure 53 [74].

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Figure 52: Coated Ti with FG CNT/HA composite [74]
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Figure 53: SEM image of (a) pure HA, (b) FG CNT/HA composite after 7 days of cell-culture [74]
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Y. Yang proved that addition of SiO2 to HA enhance the crystallinity, reduce cracking and exhibited
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better wettability than pure HA. The HA doped with SiO2 coating showed 14.5% increase in bone in-
growth, Figure 54 compares the SiO2-HA coating with pure HA [70]. The application of self-fluxing
alloys – alloys containing Al and Si – result in sound and crack-free coatings. The Al and Si oxidize
during laser cladding process, float at the surface, and protect the coating. These self-fluxing
additions minimize the oxidation of the substrate and the clad which may affect the bioactivity of
the implant [124].

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Figure 54: SEM and EDX of (a) pure HA, (b) 25% Si-HA [70]
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Not many studies focused on coating SS with bioactive materials using laser cladding technique. Q.
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Wei studied the selective laser melting of SS/nHA composite implant to offer uniform metallurgical
bonding of metal and ceramics. The nano-HA powder showed better bioactivity performance [125].
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They reported that increasing the laser scanning speed decreases the degree of cracks [126]. Fathi et
al. investigated the coating of 316L SS with pure HA, pure Ti, and double-layer coating of Ti and HA.
The double-layer showed positive improvement in corrosion resistance behavior compared to the
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other specimen [127]. M. R. Mansur et al. proposed composite coating of HA and TI6Al4V on SS. The
study revealed that Ti diffused into the substrate in the heat affected zone. At the top layer, Ca/P
ratio was 1.66 which is near to the human bone composition. They found that the suitable energy
density of laser was below 167 J/mm2 [22].
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Functionally graded materials (FMGs) approach was proposed because the HA coating deteriorates
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during working period due to poor interface bonding. This method reduces the dilution rate of HA
and reduces the cracking possibilities. M. A. Hussain proposed a hybrid mixture of HA, 316L SS and
CNT to build FGMs, Figure 55 shows SEM morphology of the resulting coating layer. The HA powder
was 50% micro-sized and 50% nano-sized to increase the density of the HA. The proposed coatings
showed increased hardness and enhanced mechanical properties [128].

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Figure 55: HA/316L SS composite coating layer (white particles are 316L SS and grey color is HA) [128]

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Li H. C. et al. investigated the usage of CaO-SiO2 as coatings on Ti6Al4V and the effect of addition of
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CeO2 and Y2O3. The addition of rare earth oxides refined the microstructure, reduced the loss of
weight, and increased the bonding strength between coating and substrate, and improved the
degradability of the sample [9], [69]. In cladding process using bioactive ceramic, CaO is formed
which is considered toxic for osseoblast. To reduce the CaO content, 5 mol% ZrO2 was added. It was
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noticed the formation of CaZrO3 and the CaO phase disappears [129].

Reviewer comment 2
M. Mansur et al. proposed HA and Ti6Al4V composite coating to obtain stable HA coating. The
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resulted coating showed better adhesion as well as more stable HA. The analysis of the coating
showed Ca/P was 1.67 which is exactly the same of human bone composition [130].
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5.4.2. Bioglass
When cladding HA on metallic substrate using LCT, the high temperature levels cause the
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decomposition of the HA (above 1300 °C) [56]. This problem causes lower bioactivity of the
developed HA coating. Bioactive glass 45S5 and S520 proved higher stability than HA at high
temperatures [11][131]. The simulated body fluid test showed that bioactive glass S520 is more
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appropriate than 45S5 in laser cladding rapid prototyping [80].

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Bioactive glass S520 was successfully cladded on Ti substrate using LCT. It is noticed that preheating
the substrate reduced cracking in the coating layer and reduced the laser power. The preheating of
the substrate reduces the cooling rate which improve the cracking resistance. M. Krzyzanowoski et
al. found that consequent layers of bioactive glass induce less cracking tendency [132].

R. Comenana et al. showed that bioactive glass S520 is most suitable to clad Ti6Al4V by LCT as the
bioactive glass S520 showed less tendency to cracking than 45S5, and have higher bulk strength
(S520 was 355 MPa, while 45S5 was 302MPa). They found that higher surface roughness enhances
adhesion with bones. Formation of TiP enhanced the coating adhesion with the substrate [123].

N. Moritz et al. proposed non-uniform bioactive glass multilayer coating. The coating was droplets of
bioactive glass on local points as shown in Figure 56, which interface with bones, and sufficiently

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adhered to the substrate. This coating technique reduced the stresses and resulted in crack-free
coating. The laser power was reduced by 30% in the successive layers [6].

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Figure 56: Proposed droplets of Bioglass coating [6]
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5.4.3. New approaches of cladding bioactive material on metallic implants

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LCT provides in situ fabrication of bioactive coating on metallic substrate. This approach lead to
better controlled composition, microstructure and enhanced adhesion. D. Wang et al. proposed in
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situ prepared CaP coating on pure Ti. The authors investigated the addition of pure yttria (Y2O3) to
improve the mechanical properties, and sodium silicate (Na2SiO3) as adhesion enhancer. The tensile
strength of the clad coating reached 68 MPa [9]. The same author proposed in situ prepared HA
coating using calcium carbonate (20 wt. %) and calcium hydrogen phosphate (80 wt. %) powders. To
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improve the bonding between coating and substrate, transitional layer of 50 wt. % Ti with 50 wt. %
of the above mixture powders was first layered [131] [133].
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Dongjiang Wu et al. proposed ultrasonic assisted laser cladding process of yttria stabilized zirconia to
modify the microstructure and control dilution characteristics. The dilution rate between the
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substrate and coating increased (53.09%) when ultrasonic vibration is applied. While the dilution
rate was 37.37% for laser cladding without ultrasonic applied. The utilization of ultrasonic vibration
increase the clad depth, improve coating microstructure, enhance linear element transition, and
increase the dilution rate that affect the bonding strength [134].

As a conclusion LCT is promising technique for coating metals with bioactive materials. LCT provide
metallurgical bond, create full-dense coating, reduced HAZ and is cost-effective process. However,
LCT has many drawbacks and further studies are needed to overcome them. LCT involves formation
of porosity in clad which reduces the strength of the structure [121]. Also, cracking and delamination
of coating may take place due to thermal expansion difference between coating and substrate [122].
The process parameters should be carefully chosen to overcome the decomposition of bioceramics

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(as HA) due to high temperature induced, besides to increase the crystallinity of the developed
coating [66].

5.5. Plasma electrolytic

electrolytic oxidation (PEO)
Plasma electrolytic oxidation (PEO) - also known as micro-arc oxidation - is a relatively convenient
technique for producing a micro-porous, rough and hard coatings on light materials such as Al, Ti,
Zr, Mg, Ta and their alloys [135]. The PEO technique has been gaining an increasing interest recently

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as it could provide superior adhesion between the coatings and the substrate and formation of high
crystalline coatings with porous surface morphologies [136], [137]. Moreover, the PEO process is a
low cost, simple to operate, eco-friendly and versatile [138]. The coatings produced by this
technique can possess a wide thickness range, providing an effective wear and corrosion protection

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to the light materials. With this technique, protective as well as multifunctional coatings can be
produced by adjusting the process parameters. PEO treatments are usually carried out in apparatus

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composed of a conventional electrolytic cell and power supply with high voltage output [139].

In a typical PEO process, coatings are deposited onto light materials from an aqueous electrolyte by
applying high voltage/current between the anode (light materials) and the cathode (usually stainless

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steel of larger area). The electrolyte dissolves in water dissociates to form anions and cations. Owing
to a high electric field between the electrodes, anions and cations migrate towards the anode and
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cathode respectively. At the anode, the oxidation of the sample begins by forming an insulating layer
on the anodic surface, Figure 57 shows typical apparatus used for PEO process. With further increase
in the applied voltage, the current is forced to pass through the coating. Subsequently, the high
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intense electric field is generated around the samples, thereby resulting in micro-arc discharges on
the entire surface immersed in the electrolyte solution. The ensuing micro-arc discharge event
produce high temperature, which assist the oxide layer to be sintered and further incorporation of
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elements from the electrolyte solution. The coating is deposited across the whole surface immersed
in the solution without altering the bulk properties [138].
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Figure 57: Micro-arc oxidation technique setup

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The PEO process and the final coating characteristics are highly dependent on several factors,
including the electrolyte composition/concentration, substrate materials, electrical parameters
(voltage and time) and geometry of the electrolytic cell [139]. It should be borne in mind that these
factors are essentially interdependent making the process quite complex.

5.5.1. PEO coatings derived HA coatings

Before 1995, the available reports on the PEO coatings are majorly concerned with producing highly
adherent oxide ceramic coatings with different chemical compositions on Al and Mg for anti-

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corrosion and anti-friction applications [140]. The application of PEO has been recently expanded
into the biomedical area due to its micro-porous and adherent layer formation on the metallic
substrate. Ishizawa et al. [141], [142] were the first research group to make use of PEO process for

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the preparation of HA layer on titanium substrate. But unfortunately they are not successful using
only PEO process. The entrance mechanism of Ca and P ions into oxide film and preparation of HA
via PEO process on the light material substrates have been considered as a difficult and complex.

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Generally, PEO process is considered as a multifactor controlled process and these factors have
direct influence on the quality, structure and composition of PEO coatings [143].
The process where HA is directly produced using PEO technique without the need of subsequent
treatment is called single stage process. The formation of HA over the oxide layer produced via PEO

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process is possible using long treatment time and voltage. Durdu et al. demonstrated that by
increasing the deposition time, the coating thickness ranging from 16-63 μm and the average pore
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sizes of 1-20 μm can be obtained (Figure 58). The increased in coating thickness and pore size was
attributed to variation in deposition time [144].
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Figure 58: Surface morphologies of PEO coatings: (a) 1 min, (b) 5 min, (c) 10 min, (d) 20 min, (e) 40 min, (f) 60
min and (g) 120 min [144].
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Deposition at high voltage and time improved the surface roughness, porous structure and HA
crystallinity of PEO coating. However, the incorporation of HA which was accomplished using high
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deposition time and voltage has some limitations. When increasing the amount of HA in the oxide
film by increasing either voltage or time, cracks were generated and failure within the coating
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followed (Figure 58e). Moreover, the obtained HA produced was often not a single phase but
contained by-products such as TiP2 [144], CaTiO3, CaO or Ca3(PO4)2 [145], [146].

To increase crystallinity of the films, further treatment using hydrothermal treatment (HT) or by
immersion in simulated body fluid (SBF) is held. It is a known fact that HA could be grown directly
over the obtained TiO2 layers using PEO process, but the growth rate is usually very low and the
amount of HA is small. Generally, HA produced by PEO treatment is usually of low crystallinity and
the coated amorphous is not as stable and bioactive as crystalline HA [147]. Owing to this, further
hydrothermal treatment is usually carried out to transform amorphous calcium phosphate to the
crystalline HA. When HT is applied after PEO treatment, the Ca2+ and PO43- ions from internal layer of
amorphous coating can successfully diffuse to the coating surface and dissolve into the solution
during HT and finally precipitate on the outer layer with higher degree of crystallinity. The
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hydrothermal treatment is performed by placing the PEO coated samples in the bottom of autoclave
or in pressure controlled reactors containing neutral or alkaline aqueous solution and treated
hydrothermally within the temperature range of 100-250 oC for 2-24 hrs at pH 7-11 [148], [149].
Figure 59 reveals the surface morphologies of the as-prepared TiO2 films after pre-immersion in 0.1,
1, and 2 M K2HPO4 for 10 min and then soaking in SBF solutions for 1, 2, 4, and 9 days [150].

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Figure 59: Surface morphologies of the PEO-produced TiO2 films and those after pre-immersing in 0.1, 1, and 2
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The micrographs of the obtained coatings show the existence of the HA with a thickness layer of
about 0.6 μm after immersion in SBF. It was shown that simple pre-immersion of oxide layer in 2 M
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K2HPO4 solution assisted the growth and nucleation of HA after soaking in SBF solution for less than 1
day. The content of HA increased with increasing the soaking time. The growth of HA after pre-
immersion in K2HPO4 solutions was attributed to the porous oxide film and adsorbent of HPO4-2
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groups on the oxide surface. However, the process for obtaining HA over TiO2 is cumbersome and
time consuming and moreover, the hydrothermal treatment of PEO layer reduces the interfacial
bonding strength because of introduction of additional phase [142].
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At the current stage of our knowledge, it is difficult to draw a conclusion on the applicability of PEO
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to produce hydroxyapatite coating without introduction of subsequent treatment. Moreover, PEO

technique results in formation of porosities which may lead to corrosion and delamination of the
coating because of the penetration of the body fluids. In addition, this technique is not suitable to
coat bioactive materials on SS or Co-alloy substrate. So, further treatments are needed to densify
the coating which in turn may lead to cracks. These cracks reduce the lifetime and durability of
implant [151].

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6. Conclusion
There is wide variety of metallic biomaterials introduced. Ti, Co and SS alloys are the most popular

Reviewer comment 3
alloys used in biomedical implants due to their excellent mechanical behavior. Nickel-free SS show
promising potential in bone-implants with improved mechanical and biocompatibility properties.

Recently, the researchers considered the BMG alloys in biomedical applications because of their
superior wear, corrosion and biocompatibility especially, Fe, Zr and Ti-based BMG. However, the lack
in fatigue properties and limitations to fabricate in large sizes are the main challenges for application
of BMG in bone-implants.

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The metallic alloys failed to show bioactivity properties and to sustain their mechanical properties in
corrosive media, which result in reduced durability. In addition, the studies reported hazardous ion
release from some metallic alloys when implanted in human body.

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In the other side, bioceramics proved superior bioactivity and biocompatibility properties, as well as
corrosion resistance. The studies reported the excellent osseointegration and osseoconduction
which promotes the healing of fractured and damaged bones. The discovery of HA and Bioglass was

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breakthrough in the biomedical industry and they are the most common used. However, the
bioceramics exhibited poor mechanical properties and brittleness which limits their application in
load bearing implants.

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Many techniques have been developed to coat metallic substrate with bioactive materials to
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combine the mechanical properties of metallic alloys and bioactivity of HA and Bioglass, besides
preventing further ion release of hazardous elements. The techniques covered in this review are
plasma spraying, sol-gel coating, PVD, micro-arc oxidation, and laser cladding.
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Currently, only plasma sprayed HA coating is approved by FDA and further researches are needed to
improve the properties of resulted coatings by different techniques which may offer better adhesion
or higher stability for the coating. The research trend is to present improved performance and
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durability of biomedical implants as the current technique still lack to meet these objectives.
TE

7. Research gap
EP

Recently, many research works focused on developing materials for bone-implants with longer life-
span (more than 25 years). More studies and investigations should consider new developed alloys as Reviewer comment 1
Ni-free SS and new Ti-alloys as TiAlNb which offer lower ion release and less hazardous effect. Also,
C

more studies and investigations are needed to improve the toxicity and biocompatibility of Co-alloys.

The current implants life is 20-25 years and the objective is to reach 40 years to minimize the
AC

revision surgeries. However, the coating techniques were presented, are still lack meeting higher
life-span because the lack in improved adhesion strength. The improvement in adhesion strength
will enhance the durability and will overcome the problems of coating separation and lamination
during implanting process. More studies should focus on depositing Bioglass on metallic substrate
using different techniques as Bioglass exhibited promising potential in biomedical applications. Also,
composite HA/Bioglass coating needs more investigation to obtain more stable coatings.

A new trend is to develop coatings from BMG on conventional used metallic bone-implants to
enhance the wear and corrosion resistance. However, BMGs need more investigations to stabilize
their amorphous phase after post processing of the coating.

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 ACCEPTED MANUSCRIPT
Acknowledgment
The authors would like to acknowledge King Fahd University of Petroleum and Minerals (Saudi
Arabia) and University of Malaya (Malaysia) for providing the necessary facilities and resources for
this research. This research was funded by Nippon Sheet Glass Foundation (Japan) and University of
Malaya Postgraduate Research Grant (PPP) Program No. PG057-2016A (Malaysia).

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Highlights

• Review of mechanical properties & biocompatibility of most popular metallic alloys.

• Review the potential of bulk metallic glass alloys in biomedical implants.

• Review of bioceramics, especially hydroxyapatite and Bioglass, properties.

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• Review on different coating techniques of metals with bioactive layers.

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