Materials Science & Engineering C: Review

Materials Science & Engineering C 102 (2019) 844–862
Contents lists available at ScienceDirect
Materials Science & Engineering C

journal homepage: www.elsevier.com/locate/msec
Review
Review on titanium and titanium based alloys as biomaterials for T

orthopaedic applications
⁎
Manmeet Kaur, K. Singh
School of Physics and Materials Science, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India
A R T I C LE I N FO A B S T R A C T
Keywords: Variety of implant materials have been employed in various disciplines of medical science depending on the
Biocompatibility requirement of a particular application. Metals, alloys, ceramics, and polymers are the commonly used bio-
Orthopaedic implants materials. The main focus of this study is to review the various structural and microstructural properties of
Titanium based alloys titanium and titanium based alloys used as orthopaedic implants. Orthopaedic implants need to possess certain
Mechanical properties
important qualities to ensure their safe and effective use. These properties like the biocompatibility, relevant
Surface modification
mechanical properties, high corrosion and wear resistance and osseointegration are summarized in this review.
Additive manufacturing techniques
Various attempts to improve upon these properties like different processing routes, surface modifications have
also been inculcated in the paper to provide an insight into the extent of research and effort that has been put
into developing a highly superior titanium orthopaedic implant.
1. Introduction taking place are summarized in Table 1.

Biomaterials can be divided into four major classes: metals and their
Biomaterials play a very vital role in the modern day and age. In the alloys, polymers, ceramics and natural materials. These are extensively
last few decades with the advancements in medicine and material being used in different medical fields: as cardiovascular biomaterials,
processing, a large number of biomaterials have been developed with for generation of skin substitutes, in drug delivery systems and in the
properties suitable for various applications [1]. Biomaterials mainly treatment of cancer by hyperthermia [10–17]. Extensive research is
find use in orthopaedics, dental care, drug delivery, tissue engineering going on to improve upon their performance [18–33]. A number of
of skin and cardiovascular devices [2]. Before recognising any material reviews provide an insight into the properties and applications of
as an implant it is imperative to know that the said material is not bioactive glasses and glass-ceramics [34–37], metallic implants [38–40]
causing any damaging effect i.e. it should be biocompatible to the and polymers [41].
human body. Williams defined biocompatibility as “the ability of a Musculoskeletal disorders include injuries that hamper the body's
biomaterial to perform its desired function with respect to a medical movement by causing pain in joints, muscles or tendons and result in
therapy, without eliciting any undesirable local or systemic effects in tissue deterioration. Persistent pain and physical disabilities caused by
the recipient or beneficiary of that therapy, but generating the most musculoskeletal disorders have affected millions of lives all across the
appropriate beneficial cellular or tissue response to that specific situa- globe. It is expected that due to the changes in lifestyle the number of
tion, and optimizing the clinically relevant performance of that people affected by the disorders of joints and bone will increase in the
therapy” [3]. This means that the implant should not release toxic coming years. A study by Kurtz et al. [42] has indicated that by the year
substances in the body as these can cause systemic damage to the pa- 2030 it is expected that the number of total hip replacements would rise
tient [4–7]. Any material upon implantation in the human body triggers to 572,000 procedures. Also, the number of total knee replacement
some kind of response. This response is more pronounced at the tissue- procedures is expected to rise to 3.48 million. Hence, it is expected that
implant interface since the interface is more reactive than the core of there will be a rise in the demand for new and improved implants and
the material. Basically, the interface is considered as a two-dimensional as a result improvement in the quality of implant materials and treat-
imperfection where the atoms are not linked to the highest number of ment procedures is a must. Musculoskeletal problems often require
neighbours. As a result, they possess higher energy than core atoms of surgery like in the case of total joint replacement. This is where bio-
the materials [8]. The four general types of tissue-implant responses materials play a key role in bone repair and regeneration. Surgical
⁎
Corresponding author.
E-mail address: [email protected] (K. Singh).
https://doi.org/10.1016/j.msec.2019.04.064
Received 12 December 2018; Received in revised form 20 February 2019; Accepted 20 April 2019
Available online 23 April 2019
0928-4931/ © 2019 Elsevier B.V. All rights reserved.
M. Kaur and K. Singh Materials Science & Engineering C 102 (2019) 844–862
Table 1
A comparison between different types of implant–tissue interactions and their subsequent consequences [9].
Implant-tissue response Consequences
Toxic Kills cells in the tissue surrounding the implant. Also can cause systematic damage to the patient.
Nearly inert Non-adherent fibrous capsule develops to isolate the host from the implant
Bioactive Tissue- implant bond at the interface.
Dissolution of implant Implant dissolves and is superseded by the tissue
Table 2
Comparison of tensile strength, yield strength and elastic modulus of various
implants with bone.
Material Tensile Yield strength Elastic References
strength (MPa) modulus
(MPa) (GPa)
Bone (cortical) 70–150 30–70 15–30 [43]

Stainless steel 490–1350 190–690 200–210 [44,45]
Co based alloys 655–1793 310–1586 210–253 [44,45]
Titanium based 690–1100 585–1060 55–110 [45]
alloys
Dense 40–100 – 70–120 [43]
HA ceramics
Bioglass 45S5 42 – 35 [46] Fig. 2. While selecting a material for a particular application it is important to
know that the mechanical properties, physiological factors and microstructure
will affect the performance of the implant.
in various orthopaedic applications like fracture fixation, hip joint re-

placement and dentistry [47–50] and Fig. 1 gives a comparison of their
Young's modulus, an important property for orthopaedic implants.
Depending on the requirement each of these implants finds use in dif-
ferent orthopaedic applications. Table 3 gives a comparison of the ad-
vantages and disadvantages of different metallic orthopaedic implant
materials. The advancement in orthopaedic surgery has seen tre-
mendous growth in the last few years as new and improved techniques
for bone repair have been developed but still, there are some areas
where work needs to be done. Sometimes the alloys fail in the long run
owing to various reasons like corrosion, wear, mismatch of Young's
modulus with the body parts and low strength. As a result, a second
surgery becomes necessary. These revision surgeries are expensive,
painful and at times are not even successful. New metallic alloys are
being developed to overcome the issues of present implant materials. It
Fig. 1. A comparison of Young's modulus of various implants. It is evident that
is important to develop materials which are tough, corrosion and wear
the Young's modulus of all the commonly used metallic implant is quite higher
resistant, biocompatible, bioactive and can survive long periods of time
than that of the bone [45,51–53].
without failure. Hence proper knowledge about the factors affecting the
performance of implant materials is essential [56] (Fig. 2).
implants made from biomaterials are used in restoring the function of Titanium and titanium based alloys have emerged as the number
an otherwise damaged part. Various types of implant materials are one choice for orthopaedic implant materials. In the present review, the
currently in use, these have varying properties. Table 2 provides a focus is mainly on titanium and titanium based alloys as orthopaedic
comparison between the mechanical properties of commonly used or- implants, explaining their structure, microstructure, thermomechanical
thopaedic implant materials and compares them with the corre- processing, mechanical properties, influence of processing parameters
sponding values of cortical bone. Amongst metals, 316L stainless steel, on mechanical properties, biocompatibility, bone bonding, corrosion
cobalt chromium alloys, and titanium based alloys are the frontrunners and wear resistance. In the last section, causes of implant failures and
Table 3
Main characteristics of metallic orthopaedic implants.
Materials Advantages Disadvantages Application References
Stainless steel Low cost, easily available, acceptable High modulus, Temporary devices-plates and screws [45]
biocompatibility Low corrosion resistance,
Allergic reaction
Cobalt based alloys Better wear and corrosion resistance, fatigue High modulus, Total hip replacement, bone plates and [45]
strength Expensive, wires
Biologically toxic
Ti and Ti based alloys Biocompatible, corrosion resistance, fatigue Low wear resistance Total joint replacement, fracture [54]
strength, low modulus, light weight fixation elements
Magnesium based Biocompatible, biodegradable, low Young's Low corrosion resistance, hydrogen Biodegradable orthopaedic devices, [55]
alloys modulus evolution during degradation bone pins and plates
845
the surface treatments used to prevent the failure have been discussed. Table 4
ASTM standards of titanium and titanium based alloys used as sur-
gical implants in orthopaedic devices [59].
2. Titanium and titanium based alloys Alloy ASTM specification
Metallic implants have been used for biomedical applications since CP-Ti (Grade 1,2,3,4) F 67
Ti-6Al-4V (ELI) Wrought F 136
the 19th century. In the 1860's Lister [44] developed an aseptic surgical
Ti-6Al-4V Wrought F 1472
technique which was a success. Lane developed a fracture plate using Ti-6Al-7Nb Wrought F 1295
steel in the early 1900's which was later modified by Sherman by re-
ducing the stress concentration [44]. Since then metallic implants have
become an integral part of orthopaedic surgery. They are used as 2.1. Structural properties of titanium
temporary as well as permanent implants in the body. Metals possess
many properties which make them highly acceptable for bone repair. Titanium is widely used in various applications because of the
Tensile strength in case of metals is quite high better than polymers and possibility of modifying its properties by varying the alloying element
noticeably higher than most bioceramics (the exception being zirconia). composition. Titanium undergoes an allotropic transformation i.e. it
Metals are highly tough, 20 times higher than ceramics and possess a changes from one crystallographic form to another. At room tempera-
reasonable fatigue life. Metals have Young's modulus values quite close ture, it exists in hexagonal close-packed (HCP) structure and this is
to those of ceramics. However, metallic corrosion can be a problem but called alpha (α) phase. At 883 °C it changes to body centered-cubic
if carefully selected, metals can show reasonable corrosion resistance. structure (BCC) called the β phase. The temperature at which α or
Metals show the ability to alloy which means their corrosion, wear, and α + β changes to all β is called β transus temperature. The two forms of
mechanical properties can be altered and they can be made suitable for unalloyed titanium are shown in Fig. 4.
the required applications. Also, biocompatibility can be improved by Titanium alloys are categorised into five crystalline categories: α,
using those elements which show no adverse effects in the body. Hence near α, α + β, near β and β. Near alpha is very much similar to alpha
metals have proven to be quite useful for implantable device applica- phase at low temperature. On heating, it forms some beta phase
tions and this trend is not expected to change any time soon [56]. (5–10%). Alpha-beta has alpha and transformed beta phase (10–30%
Titanium is the ninth most abundant element on earth. Rutile, beta). On initial cooling near beta retains beta phase but upon heating,
brookite, and anatase are the oxides bearing mineral sources of tita- it precipitates secondary phases. Alloying elements are categorised into
nium. Crystal structure of rutile and anatase is tetragonal and brookite three groups according to the phase stabilised. Different stabilisers like
has an orthorhombic crystal structure with space group P42/mnm, I41/ Zr, O, Al, N, C have been used to stabilise various crystalline phases.
amd and Pbca respectively [57], as shown in Fig. 3. In the 1950's ti- These stabilisers can alter the stabilising temperatures: α stabilisers (O,
tanium was developed for aerospace applications but after the 1960's it Al, N, C) increase the temperature at which α phase remains stable and
has been used in surgical implants. These days, 2% of titanium is used β stabilisers (V, Nb, Mo, Ta), decrease the temperature at which β phase
in medical applications. Titanium has become so popular because of its stabilises. β transus temperature is important because heat treatments
excellent combination of strength, Young's modulus and biocompat- are carried out at some incremental temperature close to this tem-
ibility as compared to other metallic implant materials [56]. Com- perature. Below this temperature titanium contains α + β phase in the
mercially pure (CP)-Ti (F 67) and Ti-6Al-4V extra low interstitial (ELI) presence of β stabilisers, if not then there is only α phase present [68].
(F 136) are the most commonly used implants in biomedical applica- The selection of processing temperature plays an important role as it
tions. Table 4 gives the ASTM standards of different titanium and ti- controls stabilisation of different phases and their volume fractions
tanium based alloys that are used in orthopaedic devices. These are decide the mechanical and other properties of titanium alloys as im-
being used in different fields in orthopaedics: fracture repair, total hip plants. Unalloyed CP-Ti has HCP crystal structure. It is available in four
and knee arthroplasty (Table 5). CP-Ti is being used for the acetabular, grades (Table 6).
femoral and tibial component in case hip and knee arthroplasty and in
fracture fixation. These implants reduce the risk of loosening, provide
stable fixation, and good biocompatibility. In the following sections 2.2. Thermomechanical processing and microstructure of titanium alloys
important properties of titanium and titanium based alloys used for
orthopaedic applications have been summarized. Microstructure plays a crucial role when talking about the me-
chanical properties of the implants like strength, ductility, and fracture
toughness. Factors like heat treatment, chemical composition, produc-
tion history affect the microstructure to a great extent. The α to β
Fig. 3. Crystal structure of TiO2 a) rutile b) anatase c) brookite [58].
846
Table 5
Some applications of titanium, as an orthopaedic implant and its benefits.
Application Component Specification Advantages
Total Hip Arthroplasty Acetabular Tritanium primary cup (Stryker Orthopaedics,)- is a highly Modulus of elasticity close to bone, high friction co-efficient,
(THA) porous, 3-D titanium (commercially pure) metal interface [60] design improves osseointegration and reduces stress shielding
[61].
Femoral ACCOLADE II Femoral Hip System (Stryker Orthopaedics)- Decreases risk of aseptic loosening [63].
proximal region of stem is coated with PureFix HA over
commercially pure titanium plasma spray substrate [62].
Total Knee Arthroplasty Tibial and Partial porous-coated metal metaphyseal-filling sleeves (Depuy, Provides stable fixation and structural support in patients with
(TKA) femoral Warsaw, IN)- Used in revision TKA. Femoral part is made of notable metaphyseal bone loss [64].
titanium and tibial part is made from titanium alloy. Porosity is
around 50–80% [64].
Fracture fixation Humeral PHILOS plate system (Synthes, Switzerland)- Includes titanium, Provides good biocompatibility, negligible interference with
preformed, angular stable locking compression plate (LCP), blood supply of the humeral head [65], yield good to excellent
designed for internal fixation of proximal humeral fractures longer term results in 75% of the patients [66].
[65].
like alpha structure is formed whereas an intermediate cooling rate

results in basketweave morphology. High cooling rates result in
widmanstӓtten pattern and martensite pattern is observed upon water
quenching [69–72]. When the alloys are processed in the α + β phase
field below the β transus temperature the microstructure consists of
globular equiaxed α (primary) phase which has been retained to room
temperature in the transformed β matrix, the resulting structure is
called equiaxed [68]. A comparison of the properties of acicular and
equiaxed microstructures is shown in Fig. 6. Grain refinement is one of
the commonly used approaches to enhance strength of the alloys. Ding
et al. [73] studied the effect of different hot working conditions on the
microstructure of Ti-6Al-4V during thermomechanical processing. The
samples were exposed to temperatures in the range 850–1050 °C and
strain rate: 0–1.0 s−1 in order to understand the relationship between
processing, structure, and properties of the alloys. It was found that
Fig. 4. Titanium exists in two crystallographic forms. At room temperature it lamellar morphology of α phase can be divided into the following ca-
exists in HCP (α) and as the temperature increases to 883o C it changes to BCC tegories: retained prior α lamella zone, the distorted α lamella zone,
(β) form [67]. segmented α lamella zone, the diffused α lamella zone, and the sec-
ondary α lamella zone (transformed α phase) for the samples processed
in the α + β phase field. During processing in the α + β phase field, the
Table 6
mechanical deformation resulted in some degree of α → β phase
Various grades of unalloyed titanium (wt%) [68].
transformation. Fine equiaxed grain structures are considered im-
Material N C H Fe O portant because they improve the formability of titanium implants at
ASTM Grade1 0.03 0.1 0.015 0.2 0.18
low temperatures [74]. Chao et al. [75] used a novel grain refinement
ASTM Grade2 0.03 0.1 0.015 0.3 0.25 mechanism involving warm deformation of martensitic structure to
ASTM Grade3 0.05 0.1 0.015 0.3 0.35 produce ultrafine equiaxed grains. In order to produce ultrafine-grained
ASTM Grade4 0.05 0.1 0.015 0.5 0.40 titanium implants, severe plastic deformation (SPD) technique has been
used by many researchers. Equal channel angular pressing (ECAP) has
come out as a promising SPD technique. It not only improves the me-
transus temperature affects the transformation of the microstructure in
chanical properties but also the biocompatibility [76–78]. The strength
case of titanium alloys. This temperature also becomes a key factor in
of α + β and β alloys can be altered by solution treatment and aging.
deciding the kind of heat treatment required. Depending upon the
The tensile strength of Ti-6Al-4V can be increased to ~1100 MPa upon
different types of thermomechanical processing (TMP) conditions dif-
solution treating [68]. Vanadium has been found to be toxic when re-
ferent microstructures can be seen in the case of titanium alloys.
leased in the body hence vanadium free alloys like Ti-6Al-7Nb have
Titanium has to undergo the following steps during its processing:
been developed for biomedical applications. Ti-6Al-7Nb finds applica-
titanium ore is reduced to a porous form called sponge, the sponge is
tion in total hip prostheses. Fellah et al. [79] found that wear resistance
melted to form ingot, ingots are converted to mill products and sec-
of Ti-6Al-7Nb alloys with two-phase microstructure was lower than that
ondary fabrication of finished products is done by die forging, extru-
of the Ti-6Al-4V under the same testing conditions.
sion, hot and cold forming, machining, chemical milling, and joining.
Since it is possible to control the mechanical properties of an alloy
Forging and subsequent heat treatments are used to alter the micro-
by grain boundary engineering Polyakova et al. [70] studied the de-
structure and the properties of the alloys. Control over the micro-
formation mechanism of phase boundaries and the variation of me-
structure is important in order to ensure successful production of tita-
chanical properties of Ti-6Al-7Nb with the changing microstructure.
nium alloys for the specific applications. Fig. 5 shows how the working
The alloy was processed using the ECAP technique. As the strain in-
temperature affects the microstructure of different categories of tita-
creased during ECAP there was a non-monotonic variation in the den-
nium alloys.
sity of low and high angle grain boundaries of α grains. It was found
Based on various studies, it has been found that the TMP of the
that the UFG resulted in UTS value of 1210 MPa which is 20% higher
α + β alloys above the β transus temperature results in lamellar mor-
than that of hot-rolled alloy.
phology. Also, different cooling rates result in a variety of lamellar
Today the focus has shifted to β titanium alloys as they possess
structures. It has been found that for low cooling rates colonized plate-
847
Fig. 5. Different categories of titanium alloys and the effect of hot working on the microstructure [69].
850 MPa. The presence of Nb, Zr and the α′′ phase could be responsible
for the small value of the modulus. Precipitation of ω phase is also
believed to be crucial in improving the mechanical properties of tita-
nium alloys. Li et al. [84] found that superelasticity in the Ti-Nb-Zr
alloys improved because of the presence of the ω phase. This can be
because ω is a hard and brittle phase which can improve the strength of
the β phase. The reason that these β alloys have received immense
attention in the recent times is because these employ non-toxic ele-
ments with superior biocompatibility. So, a possible new approach can
be to develop a coating of these elements on the more commonly used
implants made of pure titanium and titanium alloys. In order to design a
suitable coating on pure titanium or titanium alloys, sputtering tech-
nique can be a good option. Frustos et al. [85] developed Ti-22Nb-10Zr
coatings with different β/α′′ratios using the sputtering technique. The
balance between the α, β and α′′ phase can be altered by changing the
Fig. 6. Comparison of equiaxed and acicular microstructure [68].
bias voltage. Sputtering at a bias voltage of −63 V resulted in a low
value of Young's moduls (47 GPa), high Berkovich hardness of 5.6 GPa
and bioactivity was double as compared to Ti-6Al-4V.
better biocompatibility and a lower value of Young's modulus. Attempts Ti-Nb-Ta-Zr (TNTZ) is another promising system which can be used
have been made to produce equiaxed grain structures using the ap- as a biomedical implant. Málek et al. [86] studied the effect of TMP and
propriate heat treatment because of the excellent mechanical proper- chemical composition on these alloys. The prepared alloys were sub-
ties. Geetha et al. [80] subjected three alloys: Ti-13Nb-13Zr, Ti-20Nb- jected to solution treatment (850 °C/0.5 h/water quenched) and cold
13Zr and Ti-20Nb-20Zr to appropriate hot rolling conditions in order to swaging. Depending on the Ta and Zr content different mechanisms of
describe the effect of TMP on their microstructure. Fine equiaxed dynamical recovery and dynamical recrystallization during hot forging
structure was observed in the micrographs of Ti-20Nb-13Zr and Ti- were observed. After the solution treatment, post dynamic re-
20Nb-20Zr whereas the micrographs of Ti-13Nb-13Zr revealed a mix- crystallization or dynamic recrystallization during the previous hot
ture of equiaxed and elongated α phase. Various types of strategies have forging resulted in recrystallized grains. Deformed microstructure was
been used in order to study the effect of TMP on microstructure and observed after cold swaging with grains elongated in the rod axis di-
mechanical properties. A flash thermal treatment technique was used rection. After aging treatment, the value of Young's modulus was in the
by Sun et al. [81] on the Ti-20Nb-6Zr alloys. In this technique heavily range 75–90 GPa and 50–65 GPa in the cold swaged state. SPD tech-
cold rolled samples were subjected to very short thermal treatment niques like ECAP can be used to modify the microstructure and hence
based on the flash recrystallisation. This treatment produced ultra-fine the mechanical properties of titanium alloys. Li et al. [87] used ultra
β grains along with the nano-sized α and ω phases in the β matrix. fine grained (UFG) 59Ti–36Nb–2Ta–3Zr alloy to study the influence of
Recently (2018), Ozan et al. [82] applied thermomechanical treatment SPD on its properties. The alloy was prepared by ECAP of the as-hot-
on the newly developed Ti-28Nb-35.4Zr alloys. The samples were extruded TNZT alloy. The ultimate strength and yield strength in-
subjected to solution treatment at 890 °C for one hour and afterwards creased in the ECAP processed alloys. The formation of α′′martensite
thickness was reduced by cold rolling. The treatment resulted in the phase during the initial stages of ECAP which subsequently changed to
formation of a uniform single β phase with a tensile strength of β phase through recovery during continued deformation played an
633 MPa and Young's modulus of 63 GPa. It has also been proposed that important role in influencing the behavior of the alloys. There is an-
the presence of α′phase can reduce the value of elastic modulus as they other type of TNTZ alloy composition namely Ti-Nb-Ta-Zr-O called the
are able to dissolve higher content of β stabilisers. Liu et al. [83] were gum metal because of very high strength, low Young's modulus, super
able to prepare α′phase based Ti-Nb-Zr alloys with a small amount of elasticity and super plasticity. Super plasticity is observed due to the
α′′phase. The value of modulus was very low ~39 GPa and strength was dislocation free plastic deformation mechanism [88]. Currently,
848
attempts are being made to replace the more expensive Ta with Fe and provides internal support, protects vital organs and presents an an-
Sn. Nocivin et al. [89] subjected Ti–Nb–Zr–Fe–O to TMP to determine chorage site for muscles. Also, the bone has to maintain calcium
whether it can be used in biomedical applications. The alloy was sub- homeostasis and hematopoiesis. In order to serve these functions, bone
jected to homogenization treatment followed by cold rolling and re- has to be stiff to avoid bending. On the other hand, it should be able to
crystalisation treatment. The high yield and ultimate tensile strength absorb energy hence needs to be flexible. Human skeleton can be di-
and low modulus of elasticity proved its worth as a biomedical implant. vided into two kinds of bone tissue, namely cortical and trabecular.
Mohammad et al. [90] tried to understand the influence of TMP Cortical bone shows high compressive strength because of its high mass
parameters on the mechanical and electrochemical properties of Ti- per unit volume and low porosity (10%). It provides the strength and
20.6Nb-13.6Zr-0.5V. The samples were subjected to plastic deformation rigidity to the bone. Trabecular bone, on the other hand, displays high
in the β phase field followed by solution heat treatment below β transus porosity. Out of the total trabecular bone volume around 50–90% is
temperature and then cooled at various rates. Depending upon the heat made up of pores [97]. Hence, it has a lower value of Young's modulus
treatment conditions the microstructure consisted of equiaxed/elon- and ultimate compressive strength. It allows red bone marrow and bone
gated α,β phases with different morphologies. It was suggested that vessels to come in contact with bone by providing increased surface
since the mechanical and electrochemical properties were better than area.
most alloys this can be a potential biomedical implant material. Helth To use titanium as an implant one needs to ensure that the me-
et al. [91] studied the effects of different hardening techniques to im- chanical properties are similar to those of the human bone i.e. there is
prove the mechanical bio-functionality of Tie40Nb. Hot and cold no mechanical mismatch between the bone and the implant. The elastic
rolling and various annealing treatments were used to study the var- modulus of human cortical and trabecular bone are 4–30 GPa and
iation in microstructure. Recrystallization treatment was used as a grain 0.2–2 GPa, respectively. Compressive strength values of cortical and
refinement technique which resulted in a decrease of grain size and trabecular bone are 20–193 MPa and 2–80 MPa whereas yield strength
increase in UTS. Cold rolling after recrystallization again lead to an of femoral bone and tibial bone are 104–121 MPa and 120–140 MPa
increase in the UTS value. Further aging at 723 K resulted in pre- [98].
cipitation of some α phase and increase in the UTS. Addition of certain
alloying elements results in a decrease of the elastic modulus. These 2.4. Influence of various processing parameters on the mechanical
alloys are considered new generation alloys because of their superior properties
mechanical and corrosion properties. In an attempt to design low
modulus implant Cai et al. [92] investigated the influence of indium on Mismatch of Young's modulus between the bone and implant has
the structural properties and elastic modulus of Tie40Nb. Addition of been identified as one of the major issues associated with the current
In resulted in a decrease of elastic modulus to 49GPa. In order to test implant materials. This phenomenon is called stress shielding. Under
the effect of In on the corrosion behavior of Tie40Nb, Gebert et al. [93] normal circumstances, bone carries the load by itself. When an implant
studied its behavior in the Ringer's solution. It was reported that In does is introduced in the bone, the load is shared between the bone and the
not reduce the corrosion stability of Tie40Nb alloys hence this alloy implant. So, the bone will experience reduced stress and hence will
can be considered suitable for implant applications. Pilz et al. [94] experience stress shielding [99]. According to Wolff's law, the bone
studied the effect of TMP on the microstructure of Ti-40Nb-3.5In and tries to oppose the applied load and accordingly develop the most
Ti-36Nb-3.5In. TMP included solution annealing, hot rolling, cold suitable structure. As a result, the areas of the bone that are under high
rolling and recrystallization annealing of the substance. These alloys load will have increased bone mass [100]. The areas with lesser load
showed enhanced stability of the β phase due to the addition of In. A would experience a decrease in bone mass. This decrease in bone mass
single phase β microstructure was observed for solution treated Ti- is called bone resorption and can cause failure of the implant. As dis-
40Nb-3.5In and there was no phase transformation during thermal cussed in the previous sections, CP-Ti is available in four grades. The
processing. Zirconium is a biocompatible element which results in solid amount of oxygen and iron in the four grades is different. Grades having
solution strengthening because of its higher atomic radius as compared higher interstitial content display higher strength, hardness and trans-
to other commonly used alloying elements. Málek et al. [95] alloyed formation temperature than those grades which have lower interstitial
Tie35Nb with different amounts of Zr and studied the influence of TMP content as shown in Fig. 7. Unalloyed titanium is used because of its
on its microstructure and other properties. Addition of Zr stabilised the superior corrosion resistance, primarily in applications where high
β phase and enhanced recrystallisation. The value of tensile strength, strength is not the priority. CP-Ti is basically all α phase titanium and
0.2 proof strength, Young's modulus, and hardness varied in accordance has low strength. The UTS and yield strength varies from 240 to
with the type of TMP technique (hot forging, solution treatment, water 550 MPa and from 170 to 480 MPa as shown in Fig. 7. This is because of
quenching or cold swagging) used. Ti-Nb-Mo-Zr is another promising the difference in the interstitial amount. Strength improves by in-
alloy which can be used for biomedical applications. Nunes et al. [96] creasing the amount of oxygen and iron in the alloys. Addition of these
used Ti-29Nb-2Mo-6Zr and Ti-24Nb-4Mo-3Zr alloys to study the in- alloying elements significantly improves the yield strength i.e. 0.2%,
fluence of the degree of deformation by cold rolling after homo- tensile strength, and hardness of titanium [101]. Young's modulus of
genization heat treatment. Solution treatment at 1000 °C for 24 h and the four grades of CP-Ti alloy is 115 GPa [45]. CP-Ti is most commonly
subsequent water quenching resulted in β microstructure in both the used in making dental implants. Attempts are continuously being made
alloys, whereas cold rolling induced precipitation of α′′ phase. The de- to improve the strength of various grades of CP-Ti. Most frequently used
gree of deformation affected the mechanical properties to a significant technique is solid solution strengthening especially using oxygen. But
extent. oxygen poses a problem in terms of corrosion resistance and bio-
So, from the above discussion, it becomes clear that the choice of compatibility. As a result, selective laser melting (SLM) has received a
alloying elements and the type of treatment plays an important role in lot of attention. SLM is a new technique using which a product is de-
the microstructure evolution and mechanical properties of titanium veloped by melting certain regions of the powder layers when placed in
alloys. The next section presents a comparison between the mechanical a protected environment by using a laser beam. It provides the benefit
properties of titanium implants and human bone which is very essential of high material utilisation, minimal machining and results in the
for the selection of any material as a biomedical implant. production of near-fully dense components. Attar et al. [102] used SLM
to develop CP-Ti parts starting from powder and it was realised that a
2.3. Mechanical properties of natural bone suitable combination of laser power and scanning speed was important
to melt the layers. Upon increasing the applied laser scanning speed
Human bone is a connective tissue made up of fibres and cells. Bone above 100 mm/s α′ phase was formed. Due to the formation α′ phase
849
Fig. 7. Comparison of (a) Tensile strength and (b) 0.2% yield strength of unalloyed titanium [68].
microhardness, UTS and compressive tensile strength increased to 261 manufacturing techniques like SLM and electron beam melting (EBM)
Hv, 757 MPa and 1136 MPa which is higher than the samples formed have been employed [121]. The Ti-6Al-4V alloy produced by SLM
using conventional methods. Li et al. [103] used two different laser consists of acicular α′ martensite and some β grains unlike the equili-
powers of same energy density to fabricate CP-Ti parts using SLM brium α and β phases present in alloys formed by conventional means
technique. Depending upon the laser power the samples displayed [122]. SLM has been extensively used to improve the mechanical
different microstructure, texture and mechanical properties. It was properties of Ti-6Al-4V like yield strength and microhardness
found that CP-Ti formed using a laser of higher power was strong tex- [123,124]. Further, EBM has been used to improve the mechanical
tured, with isotropic mechanical properties and ultimate compressive properties like ultimate tensile strength, micro hardness and yield
strength ~1.1GPa. This was due to the formation of α′ phase present in strength of Ti-6Al-4V. The microstructure of Ti-6Al-4V produced using
the samples formed using laser of higher power because of higher EBM consists of columnar β grains along with α + β grains present
cooling rates. Laser engineered net shaping (LENS) is another com- within the β grains [125]. EBM and SLM can be used for improving the
monly used additive manufacturing technique. Attar et al. [104] pre- fatigue performance of the Ti-6Al-4V implants [126,127].
sented a comparative study of CP-Ti produced by SLM, LENS and In the last decades efforts towards developing scaffolds that can
conventional methods. Based on the hardness and compression tests, it imitate the properties of human bone have grown immensely. Porous
was concluded that SLM presents superior mechanical properties than titanium implants possess a low value of elastic modulus and also
the other two techniques. In another study by Palán and Zemko [105] provide space for better ingrowth of bone. Takemotoa et al. [128]
grade 2 and grade 4 titanium were passed through the continuous produced porous bioactive titanium with 40% porosity. Although the
forming severe plastic deformation (SPD) machine followed by cold implant was found to have a relatively low value of yield strength and
working. SPD is a term used for techniques that provides ultra large fatigue strength but was strong enough to tolerate loading within the
plastic strain to the test material. CONFORM is one of the most com- limit. This material displayed low value of compressive modulus
monly used SPD process. This increased the UTS from 480 MPa to (4.7 GPa) and showed better bone ingrowth. Taniguchi et al. [129]
1050 MPa for grade 2 and from 650 to 1250 MPa for grade 4 titanium. investigated the effect of pore size on bone in-growth in rabbits. They
Apart from CP-Ti other α and near α alloys have not been widely used found that porous titanium implants with a pore size of 600 μm dis-
in medical applications. This is mainly because of their lower strength played better fixation ability than those with a pore size of 300 μm and
as compared to α + β and β titanium alloys. 900 μm. Chang et al. [130] developed porous titanium with 70% por-
α + β alloys have been the most frequently used orthopaedic im- osity. The average 3D pore size was 188–390 μm. The Young's modulus
plants. Although they have certain limitations which have shifted the and yield stress of the three samples was close to Young's modulus and
focus to β alloys still they are quite relevant. One of the important yield stress of human trabecular bone. It was found that titanium with
properties when talking about orthopaedic application is Young's relatively large pores (Ti 313 and Ti 390) displayed better bone in-
modulus. Fig. 8 gives a comparison of Young's modulus of different growth. Li et al. [131] developed Ti-6Al-4V reticulated meshes using
titanium alloys. Ti-6Al-4V and Ti-6Al-4V ELI (extra low interstitial) are EBM method to study the effect of cell shape on mechanical properties
the most commonly employed titanium alloys. The Young's modulus, of the alloys. It was found that for porosities in the range 88–58% the
0.2% yield strength and UTS of Ti-6Al-4V is 110 GPa, 860 MPa and values of compressive strength and elastic modulus came out to be
930 MPa [45]. Although the strength of α + β alloys is better than that 10–300 MPa and 0.5–15 GPa, respectively. However, the porous struc-
of CP-Ti but the value of Young's modulus is quite high which causes tures suffer from certain drawbacks like lower strength. In order to
stress shielding. Also, aluminium and vanadium have been reported to overcome these issues Fousová et al. [132] developed Ti-6Al-4V using
be harmful to the human body hence attempts are being made to find a SLM with a gradient in their structure. When the alloys have porosity
more biocompatible replacement of these elements. Alloys like gradient the mechanical properties can be optimised to a certain sui-
Ti–6Al–7Nb and Ti–5Al–2.5Fe have been developed by replacing the table value. This can be a promising technique since the samples pos-
toxic vanadium. Ti–6Al–7Nb has strength similar to that of Ti-6Al–4V. sess a very low value of Young's modulus i.e. 30.5 ± 2 GPa and the
It shows better ductility and better corrosion resistance [113]. values of tensile yield strength and UTS were slightly higher than those
Ti–5Al–2.5Fe also shows high UTS and yield strength: 1020 MPa and of hot rolled materials. A review by Wang et al. [133] presents an in-
895 MPa, respectively [114]. Fatigue limit is another important quan- sight into the topological design and additive manufacturing of porous
tity whose variation with alloying elements is shown in Table 7. In metals for scaffolds. Triply periodic minimal surfaces (TPMS) have
order to improve the properties of α + β titanium alloys additive become appealing candidates for designing scaffolds. Yan et al. [134]
850
Fig. 8. One of the prime difference between the α + β and β alloys can be seen in terms of the values Young's modulus, as is clear from the figure [45,106–112].
Table 7 alloy porous and alter the level of porosity in the alloy. Porosity de-
A comparison of fatigue strength of different titanium alloys. creases the strength of the bonds as it increases the bond length. Wang
Implant type Fatigue limit MPa (in 107 cycles) Reference
et al. [144] fabricated porous Ti-10Nb-10Zr with different porosities.
These alloys achieved higher strength than the unalloyed Ti scaffolds
CP-titanium 430 [115] with same porosity. The alloy with 59% porosity exhibited elastic
Ti-6Al–4V 500 [116] modulus and plateau stress of 5.6 GPa and 137 MPa, respectively.
Ti–6Al–7Nb 500–600 [117]
Different additive manufacturing techniques are being used for de-
Ti–5Al–2.5Fe 580 [118]
Ti-13Nb-13Zr 500 [119] veloping new and improved β alloys. SLM has gained popularity be-
Ti-12Mo-6Zr-2Fe 525 [120] cause it allows meticulous control over the pores size and porosity,
hence over the mechanical performance of an implant. It has been re-
ported that addition of tantalum into titanium results in an increase in
and Ataee et al. [135] have developed high porosity TPMS scaffolds the tensile strength and decrease in the modulus [145]. Sing et al. [146]
using SLM and EBM techniques, respectively. Yan et al. found that used selective laser melting to fabricate TiTa alloys with 50 wt% of each
TPMS lattices exhibited a low value of modulus in the range element. The microstructure was made up of randomly oriented
0.12–1.25 GPa which is similar to the modulus of trabecular bone. Ti- equiaxed grains of β titanium and tantalum. The UTS and elastic
6Al-4V gyroid scaffolds developed by Ataee et al. had elastic modulus modulus of the samples came out to be 924.64 ± 9.06 and
and yield strength in the range 637–1084 MPa and 13.1–19.2 MPa, 75.77 ± 4.04 GPa, respectively. Yan et al. [147] developed TiTaZr
respectively. Ataee et al. [136] also developed ultrahigh strength CP-Ti alloys using SLM. The microstructure was initially made up of α phase
gyroid scaffolds using SLM technique. The value of elastic modulus was which changed into β and finally into the α + β phase. The elastic
of the order of modulus of trabecular bone. SLM has also been used on modulus of Ti-15Ta-10.5Zr came out to be 42.93 ± 3.28 GPa, which
another commonly used α + β alloy Ti-6Al-7Nb [137]. Chlebus et al. was close to the modulus of human cortical bone. The interest in new β
[138] tried to understand the influence of SLM technique on the mi- type alloys like Ti-24Nb-4Zr-8Sn is increasing because of their low
crostructure and mechanical properties of Ti-6Al-7Nb. It was found that elastic modulus and non-toxicity. Zhang et al. [148] used SLM to pro-
the layered microstructure of the material results in significant aniso- duce Ti-24Nb-4Zr-8Sn and found that the value of Young's modulus,
tropy in the value of Young's modulus and mild anisotropy in the other yield strength, and UTS came out to be 53 ± 1 GPa, 563 ± 38 MPa
mechanical properties. and 665 ± 18 MPa, respectively. Yang et al. [149] also fabricated Ti-
In recent times focus has shifted to β titanium alloys which are also 24Nb-4Zr-8Sn using SLM and concluded that this improves the UTS and
called the second generation of titanium alloys. These alloys have a low uniform elongation. Chen et al. [150] studied the microstructure and
value of Young's modulus hence could solve the problem associated mechanical properties of Ti-37Nb-6Sn fabricated using SLM. The sam-
with stress shielding. Another benefit is that these have better corrosion ples possessed a low value of elastic modulus (66 GPa) and high value
resistance and biocompatibility because of the absence of vanadium. of UTS (891 MPa). The fine grains and limited defects resulted in the
The alloying elements are niobium, zirconium, molybdenum, tantalum, high value of strength and the presence of α′′ martensite phase produced
and iron. These alloying elements cause an increase in the UTS and a low value of elastic modulus. EBM technique is also extensively being
decrease in the Young's modulus [139–141]. A new alloy Ti-25Ta-25Nb used to produce β implants. Liu et al. [151] used EBM to manufacture
has been developed with the value of Young's modulus calculated as Ti-24Nb-4Zr-8Sn alloys with 70% porosity. These implants showed very
55GPa which is very small and UTS is 530 MPa [142]. The Ti–Nb–Zr–Ta low value of Young's modulus (0.7 ± 0.1 GPa) and compressive
(TNZT) alloys also have very low Young's modulus (~55 GPa) [45]. strength was higher than Ti-6Al-4V with same 70% porosity. A com-
Guo et al. [143] synthesized Ti-33Nb-4Sn, a metastable β-type Ti alloy. parison of the mechanical properties of titanium alloys produced by
The β phase was retained at room temperature by the higher grain different additive manufacturing techniques is shown in Table 8.
boundaries and high density of dislocations. The material was subjected With the increasing porosity Young's modulus and compressive
to cold rolling and annealing and displayed excellent mechanical strength both decrease [152]. This decrease in strength can be com-
properties: elastic modulus (~36 GPa) and ultimate strength pensated by adding a biodegradable polymer. Poly-L-lactic (PLLA) acid
(~853 MPa). Another way to reduce Young's modulus is to make the was filled into the pores of porous titanium. The tensile Young's
851
Table 8
Mechanical properties of titanium alloys produced by different additive manufacturing techniques.
Implant type Manufacturing technique Young's modulus (GPa) UTS (MPa) Yield strength (MPa) References
Ti-6Al-4V Standard 110 930 860 [45]

SLM 131.51 ± 16.40 1165.69 ± 107.25 1055.59 ± 63.63 [146]
CP-Ti SLM 111.59 ± 2.65 703.05 ± 16.22 619.57 ± 20.25 [146]
TiTa SLM 75.77 ± 4.04 924.64 ± 9.06 882.77 ± 19.60 [146]
Ti-15Ta-10.5Zr SLM 42.9 3 ± 3.28 805.32 ± 19.25 768.61 ± 16.09 [147]
Ti-24Nb-4Zr-8Sn Forged - 840 - [149]
SLM(101) - 950 - [149]
EBM (70% porosity) 0.7 ± 0.1 35 ± 2 - [151]
Ti–37Nb–6Sn SLM 66 891 ‐ [150]
modulus and tensile strength remained almost constant with PLLA ad- 2.5.2. Vanadium
dition but the compressive 0.2% proof stress (the point where 0.2% Vanadium can have both positive and negative effects on the body.
plastic deformation has occurred) improved [153]. In another attempt On one hand, it has been reported that vanadium can exert anti-diabetic
to reduce Young's modulus and improve the strength, Kopova et al. effects. However, it has also been associated with gastrointestinal dis-
[154] developed Ti–35Nb–7Zr–6Ta–2Fe–0.5Si. It yielded above comfort and decreased body weight gain [167]. Animal studies have
700 MPa, UTS was above 800 MPa and Young's modulus value ~86 GPa shown that exposure to vanadium and its compounds can be carcino-
which is still significantly lower than that of Ti-6Al-4V. Haghighi et al. genic [168]. Vanadium is one of the most commonly used alloying
[155] designed a Ti-Fe-Ta alloy whose microstructure was composed of elements in titanium based alloys. These toxic effects of vanadium
β and α′′ phases. It was reaslised that elastic modulus decreased with the cause concerns regarding the use of Ti-6Al-4V. A study has revealed a
increasing Fe and Ta content. Ozan et al. [156] developed a new series connection between vanadium release and implant failure [169]. At-
of TiTaZrNb alloys using cold-crucible levitation melting (CCLM) tempts have been made to replace vanadium with a more biocompa-
method on order to improve the strength. Fatigue properties are also of tible element.
utmost importance for any implant material and they depend on the
microstructure of the material. Apart from the microstructure fatigue 2.5.3. Aluminium
properties are also dependent on the surface conditions. β titanium Aluminium has little function in the human body. It is toxic in high
alloys can be considered superior than α + β alloys in a number of ways doses. Aluminium can be linked to a number of diseases. It can cause
but their unsatisfactory fatigue strength is a drawback. One way to neurotoxicity under certain conditions. A study on mice revealed that
enhance the fatigue strength by preserving low Young's modulus is to aluminium can cause impairment of motor functions. It can also reduce
add Y2O3 particles which inhibit the sliding of dislocations [157]. Liu spatial memory capacity [170]. Aluminium accumulation is also con-
et al. [158] introduced oxygen into Ti-29Nb-13Ta-4.6Zr to improve its sidered harmful because studies have shown possible links to Alzhei-
fatigue properties. With the increase in oxygen content the fatigue limit mer's disease [171]. Aluminium is also associated with kidney diseases.
increased. Presence of oxygen induces strain fields which inhibits the High levels of aluminium can slow bone remodeling and eventually
dislocation motion. This decreases the length of the slip line and as a cause osteomalacia [172].
result, increases the opposition to fatigue crack initiation. TNTZ alloy
with 0.7 mass% oxygen displayed excellent fatigue limit of ~635 MPa,
2.5.4. Titanium-based alloys
high tensile strength ~1100 MPa and Young's modulus ~76 GPa.
These alloys display better biocompatibility than stainless steel and
cobalt based alloys. This is because of the excellent corrosion resistance
2.5. Biocompatibility of titanium based alloys and their alloying elements of titanium based alloys. Concerns have been raised about the use of
aluminium and vanadium as the alloying elements because of their
The most important alloying elements for titanium are Al, V, Nb, harmful effects upon release into the body as discussed in the above
Mo, Zr, Ta. This section presents a summary of the biocompatibility of sections [173]. In one case a patient with Ti-6Al-4V plate developed
titanium and the alloying elements. systemic dermatitis and implant failure [174]. Although Ti-6Al-4V is
considered to be highly corrosion resistant but no material is com-
pletely bioinert. Ion release can cause allergic reactions in some cases.
2.5.1. Titanium Hence, extensive efforts have been put into developing titanium alloys
Titanium has long been considered inert and safe for human use. It with relatively safer elements. Niobium, tantalum, zirconium are few
produces minimal side effects in the human body. This can be seen as examples which are considered safer than aluminium and vanadium.
one of the major reasons for using titanium as an implant. But no metal Titanium, niobium, tantalum, hafnium, and rhenium were implanted in
is completely inert in-vivo as it undergoes some corrosion with respect rats and displayed good biocompatibility [175]. β alloys were then
to time. Over the years there have been reports indicating that titanium developed with the hope of improving the biocompatibility of the al-
particles could be harmful [159]. When titanium is implanted in the ready existing titanium alloys.
body internal exposure is increased. Titanium ions accumulate around
the dental and orthopaedic implants. Peri-implant tissues have 100–300 2.6. Process of bone bonding
parts per million (ppm) of titanium concentration. This is often fol-
lowed by discoloration [160–164]. In a study on titanium implants, it Whenever an implant is introduced into the body it will always
was found that increased levels of titanium were found in lungs which generate an inflammatory response from the human body. There could
were 2.2–3.8 times the mean of the animals with no failure. Also, in be reddening or swelling post implantation in the body. This reddening
regional lymph nodes the titanium concentration was 7–9.4 times marks an increase in the blood supply. Blood brings in the cells which
higher than mean of the levels in animals with successful implantation are involved in the repair (Fig. 9). The cells have different shapes and
[165]. Dental implant patients are susceptible to titanium allergy. Al- they move from blood to the tissue to handle the foreign substance like
though the prevalence is low but the patients showing post-operation implants. The granular cells are called polymorphs or microphages. The
allergy compatible response are at higher risk [166]. neutrophils are present in large numbers to ingest bacteria. Non-
852
Fig. 10. After the implantation a CHA layer is formed on the surface of the
Fig. 9. Different white blood cells involved in the repair post implantation and implant, followed by collagen fibres entering this layer and forming a bond.
the process of encapsulation of implant [9].
formed as a result of the ion exchange reaction that occurs between the
granular are the second type of cells and they have round nuclei. bioactive implant and the body. This CHA layer is very similar to the
Lymphocytes are responsible for producing antibodies. Increase in the mineral phase of the bone. There is a natural affinity between the
number of lymphocytes signifies allergy. Monocytes move from the collagen and the CHA. They have such a strong desire to blend together
blood to the tissue to ingest foreign bodies. Upon reaching the affected that upon formation of activated carbonate apatite layer the collagen
tissue it forms macrophages. Macrophages produce enzymes which fibres of the bone enter this layer forming a biological bond [179].
digest the debris when it is small in quantity. When the debris is large, Titanium implants unlike other metal implants bond with the bone
which happens in the presence of an implant the macrophages are not and are not encapsulated by a fibrous tissue which is a major difference
successful and possibly die. The macrophages are activated and gen- between the titanium based implants and other metallic implants.
erate cytokine signals. The activated macrophages affect the fibroblasts. Biological processes produce hydrogen peroxide and its interaction
Fibroblasts produce collagen molecules which form a capsule around with surface oxide can form a titanium-peroxy gel on the surface. This
the implant. This capsule thickens as long as the phagocytic activity can be a possible reason behind the bioactivity of titanium [180]. To
continues [9]. An important fact to be noted is that titanium and its speed up the process titanium implants are sometimes pre-treated. The
alloys show minimal encapsulation whereas stainless steel and CoCr key question still remains how does a CHA layer develop on the surface
alloys, give rise to a thicker fibrous capsule (up to about 2 μm thick) of titanium implants. In order to get answers, an experiment was done
[56]. Implants with thick fibrous encapsulation are isolated and are in which CP-Ti plates were soaked in 4 M NaOH for 24 h and then he-
unable to adhere to the bone. Owing to the lack of bioactivity these ated at 600 °C. The chemical treatment resulted in the formation of
remain as foreign materials [9]. In the case of biomaterials, the thick- apatite layer on the implant, both in-vivo and in-vitro tests [181]. It is
ness of fibrous tissue has a direct relation to its biocompatibility as well believed that chemical treatment accelerates the formation of TiO2
[176]. It is difficult to avoid fibrous capsule around metallic implants, hydrogel on the surface of titanium implant [182]. This titania hydrogel
no matter how thin it might be. A combination of thick fibrous capsule, allows apatite nucleation [183]. It then immediately grows by ab-
high amount of macrophages, osteoclasts and lymphocytes is linked sorbing calcium and phosphate ion from the surroundings and forms
with bio-incompatibility of the implant material. This thickness is a the apatite layer to which the collagen bonds.
function of the chemical and topographical nature of the surface of the One can say that in order to avoid encapsulation and to ensure
implant [177]. Most metals have this layer around them, which even- strong bonding between the bone and the implant, the synthetic nature
tually leads to loosening of the implant. To the surprise of many, tita- of the implant needs to be masked. It should be able to imitate the
nium implants display strong integration with the host bone. To un- constituents of the body. To improve the bone anchorage and bioac-
derstand the bonding mechanism, it is required to be aware of the tivity a number of surface modification techniques have been used. HA
chemistry of the bone. Bone has both organic and inorganic compo- layer can be formed on titanium substrate to improve bioactivity. A
nents. Two third of the bone weight is made up of hydroxylapatite (HA) titania buffer layer could be used to improve bonding between HA and
crystals Ca10(PO4)6(OH)2 (HA). HA is responsible for providing the titanium substrate [184]. Another technique is to use bioactive glass
bone with strength. HA is carbonated in the bone i.e. PO43− is replaced coatings on titanium alloys to improve biofixation [185]. Titanium
by CO32−.The other one-third of the weight is because of collagen fi- implants subjected to alkali based treatment displayed calcium uptake
bres. These are flexible in nature hence are able to tolerate bending. and mineralization on the implant surface [186]. It has been realised
Studies to understand the bonding between implant and bone began that surface modification by magnesium can improve bone bonding
with the bioglass. Strength of the bond is such that fracture does not [187–189]. Magnesium is widely being used to improve the properties
occur at the interface between the implant and the bone but in either of titanium implants because even the release of Mg2+ improves me-
the implant or the bone. The interface in general acts as a buffer to tabolic reaction and bone bonding. Recently (2018), Jiang et al. [190]
prevent the crack movement. There have been varying explanations developed TieMg composites to synthesize a load bearing implant with
about the type of bond between the implant and the bone. In the1970's, low Young's modulus, sufficient strength, and excellent biocompat-
a biological bonding theory was developed. According to this theory as ibility. Tao et al. [191] studied the effects of Mg, Sr and Zn substituted
shown in Fig. 10 the collagen fibres enter the bioactive implant and are HA coatings on the osseointegration in case of titanium implants. Based
responsible for strengthening of the implant. Bioactive glass was found on a comparative study on the female Sprague-Dawley rats it was
to develop a carbonated hyrdoxylapatite (CHA) layer on the surface concluded that these coating can improve the osseointegration with Sr
[178]. This step is critical to bone bonding. This bone bonding is known coating giving the best results. A number of techniques have been
as the bioactivity of the material. Biologically active CHA layer is employed to create HAP coatings on metallic implants: sol-gel dip
853
coatings, electrochemical deposition, plasma spraying and sputter

coating [192–194]. Liu et al. [195] prepared calcium carbonate coat-
ings on sandblasted and acid-etched titanium implants. It was con-
cluded that the early bone ingrowth and osseointegration improve with
calcium carbonate coatings. This could be because calcium ions cause
osteoblast response mediated by the integrin. Li et al. [196] used gra-
phene coatings to improve the osseointegration of titanium alloys. It
was found that graphene not only improved osseointegration but also
enhanced the biocompatibility of titanium alloy, hence could be a
promising material for nano-coatings for bone defect repair. Yu et al.
[197] found that Zn-doped calcium silicate coatings result in better
bone contact and improved regeneration and can be helpful in treating
osteoporotic bone tissue. It has also been found by Ma et al. [198] that
in order to obtain osseointegration in implants, 3,4-dihydroxy-L-phe-
nylalanine (Dopa) coatings can be used in osteoporotic patients. The
reason can be related to Dopa's ability to inhibit the expression of os-
Fig. 11. A comparison of repassivation time of various metallic alloys [215].
teoclastogenesis related genes. Jiang et al. [199] used a different ap-
proach when they wrapped a porous Ti layer over a dense TieMg
composite. Since the sample exhibited high compressive strength Corrosion of implants is undesirable primarily because of two reasons,
(110 MPa) and low Young's modulus (5 GPa) it can find application in it affects the strength of the material and it releases products which are
load-bearing applications. The fate of an implant also depends on the potentially dangerous for the human body. Every metal has different
inflammatory response produced in the body. It is beneficial if an im- corrosion resistance. Corrosion is not always problematic: some metals
plant has inflammation regulatory effect. Li et al. [200] incorporated upon exposure to air develop an oxide layer on the surface which
magnesium into porous TiO2 coating titanium substrate. It was con- prevents the transfer of ions from the implant to the body fluids.
cluded that magnesium can be used as an anti-inflammatory agent and Titanium is very reactive and develops an oxide layer on the surface.
can help in mediating osteogenesis. Incorporating a strontium layer The corrosion characteristics of titanium depend strongly on the sta-
over the titanium implant is believed to improve osseointegration as bility of the oxide film. The oxide layer is stable if passivation holding
strontium can decrease bone resorption and improve bone formation. current density is low. Once the surface oxide film is damaged corrosion
Porous titanium implants have received a lot of attention because they process starts again and metal ions are continuously released. Hence
are able to improve the mechanical mismatch and also allow a me- repassivation is important to stop this release of ions into the body.
chanical interlock but they are still unable to provide sufficient os- Repassivation time is different for different materials as shown in
seointegration comparable to that of the natural bone. Pulsed electro- Fig. 11. It is clear from the figure that repassivation time for stainless
magnetic fields (PEMF) therapy improves bone growth on titanium steel is more than that for titanium alloys, implying that more ions
surface [201]. Jing et al. [202] have found that PEMF stimulation can would be released from steel than from titanium alloy. This is one of the
improve bone ingrowth and osseointegration in case of porous titanium superior qualities of titanium alloys over stainless steel. Titanium oxide
implants. PEMF is able to promote activation of canonical Wnt sig- bonds strongly to the implant surface. Titanium alloys are able to tol-
naling which helps with the new bone formation. It was also found that erate the corrosive environment of the body to a great extent [216].
a hard nanostructured TiC layer provides a better bone-implant contact Corrosion potential and corrosion current densities are important
than uncoated implant [203]. quantities while comparing corrosion properties. Fig. 12 compares the
Since implant surface makes the first contact with the tissue upon average values of corrosion potential Ecorr and current densities icorr of
implantation it plays an important role in deciding the success of the Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr. In order to further improve
implantation. It has been found that rough surface results in better the corrosion resistance, titanium is alloyed with other elements.
osseointegration [204]. Ren et al. [205] used sandblasting, acid etching Adding niobium in place of vanadium improves the corrosion resistance
and anodic oxidation to fabricate a hierarchical morphology with mi- of titanium alloy as it stabilises the oxide layer and improves passiva-
croscale valleys and nanoscale tubes on the titanium substrates. The tion [218]. According to a study by Zhou et al. [219], TieTa showed
surface was completely covered with HA after being dipped in simu- better corrosion resistance than Ti-6Al-4V. This is because the Ta2O5
lated body fluid (SBF) for 14 days which shows that the modified sur- film is able to strengthen the TiO2 layer. Titanium alloys are widely
face shows commendable bioactivity. Nanostructured surfaces are also used in dental applications. These days fluoride therapy is widely used
believed to enhance osseointegration by improving the bone-implant to prevent dental caries. It has been found that corrosion in titanium
contact [206]. Salou et al. [207] showed that nanostructured surfaces alloys is dependent on the fluoride concentration and pH levels [220].
improve osseointegration in titanium implants as proved by the en- Ti–13Nb-13Zr displays better corrosion resistance in comparison to Ti-
hanced bone-to-implant contact and bone growth values as compared 6Al-4V because the corrosion products of niobium and zirconium are
to other implant surfaces. It has also been noticed that the surface oxide less soluble in human plasma than those of aluminium and vanadium.
layer can play an important role in improving the biocompatibility of Also, the oxide layer that forms on Ti–13Nb-13Zr is much more inert.
the titanium implants [208–210]. Hence various oxidation techniques The oxide layer is responsible for corrosion resistance of the material
such as thermal oxidation, alkali treatment have been employed to but it can break down leaving the implant vulnerable to corrosion. So,
improve osseointegration in case of titanium implants [211,212]. the repassivating capacity of the alloys is of utmost interest. An in-
vestigation was performed on Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr
2.7. Corrosion and wear in implants by Khan et al. [221] to study their ability to repassivate in phosphate
buffered saline (PBS) solution. It was found that an increase in pH af-
Metallic implants undergo corrosion in the body as the body's en- fected the corrosion of Ti-6Al-4V, Ti-6Al-7Nb more than that of Ti-
vironment is highly reactive. A report by Egusa et al. [213] suggested 13Nb-13Zr. With the increase in pH corrosion resistance of Ti-6Al-4V,
that an allergic reaction could by caused by titanium dental implants in Ti-6Al-7Nb decreased implying that the repassivation became difficult.
some patients. Blood and other constituents of the body fluid include Increase in pH had the opposite effect on Ti-13Nb-13Zr. This could be
several components like water, sodium, chlorine, and proteins that because of the lower solubility of niobium and zirconium ion in the
make the body's environment highly reactive for metals [214]. presence of increased hydroxyl concentrations as compared to that of
854
Fig. 12. Gives a comparison of the average values of corrosion potential (mV(SCE) Ecorr and current densities (nA/cm2) icorr of different titanium alloys [217].
aluminium and vanadium ions. The influence of pH on corrosion de- resistance. This improves corrosion resistance possibly because NiTi is
creased upon the inclusion of protein to phosphate-buffered saline nobler than Ti-6Al-4V.
(PBS) solution. Another point to be noted is that upon corrosion, Titanium alloys have a high coefficient of friction, low surface
hardness of the surface decreased. One can say that the original rutile hardness, as a result have low wear resistance. Wear in implants be-
titanium oxide surface is the hardest in all cases. comes a problem due to the fact that the wear debris results in loos-
Surface coatings play a key role in improving the corrosion char- ening of the implant and eventually causes failure. Total joint re-
acteristics of titanium alloys. Oliveira et al. [222] used plasma assisted placements (TJR) made from metal head and polymer cup are
physical vapour deposition (PVD) technique to deposit TiN and TiAlN/ susceptible to loosening of the implant. As a result, these implants have
TiAlCrN on the Ti–6Al–4V alloy. It was found that as a result of the TiN to be replaced after some years via revision surgery. Studies have
and TiAlN/TiAlCrN coatings the corrosion resistance of Ti–6Al–4V alloy proven that wear is a principal mode of failure for these implants. TJR
improved. The TiN monolayer coating displayed better corrosion re- surgeries make use of a metallic femoral head coupled with an ultra-
sistance than the TiAlN/TiAlCrN multilayer coating. The corrosion re- high-molecular-weight polyethylene (UHMWPE) acetabular cup. The
sistance of TiN is associated with its chemical inertia. Also, TiN showed problem in applying UHMWPE and Ti-6Al-4V combination for TJR lies
better corrosion resistance than TiAlN/TiAlCrN, which can be attrib- in the fact that wear rates for this combination have been reported to be
uted to the presence of aluminium as it increases the reactivity of the 35% more than that for Co-Cr-Mo alloys. Higher wear rates can be
samples. The higher thickness of TiAlN/TiAlCrN coating and a small caused by the mechanical instability of oxide film on the implant sur-
number of interfaces are also responsible for reducing corrosion re- face. External stresses can break the passive oxide layer on the surface
sistance in comparison to TiN coating. In another study by Lu et al. of titanium alloys. The exposed surface is not able to repassivate im-
[223], a nanograined (NG) layer was developed on CP-Ti (grade 2) by mediately resulting in consumption of the alloy. This poses a big pro-
the means of sliding friction and this was compared to the conventional blem in terms of application of titanium alloys in TJR. Titanium alloys
coarse-grained titanium. Studies have claimed that nanocrystalline are preferred because of their lower Young's modulus, higher corrosion
structure can quickly form a passive layer improving corrosion re- resistance and better biocompatibility in comparison to their counter-
sistance. NG titanium displays a great combination of high corrosion parts (stainless steel and cobalt alloys) but they lack in terms of wear
resistance with improved biocompatibility. This can be ascribed to the properties [51].
formation of a thicker passive layer that hindered the electron migra- Some surface modifications are used to improve the wear resistance
tion. Thermal oxidation (TO) method is used to improve the corrosion of the titanium implants. Methods like thermal treatment, ion im-
resistance of an alloy. Coating by rutile phase of TiO2 has gained a lot of plantation, physical vapour deposition coatings have been tested.
attention as it is believed that it has higher bonding strength and Thermal treatment has been used to improve the wear resistance of
thickness as compared to naturally forming oxide. Wang et al. [224] titanium implants. TO treated Ti-6Al-4V resulted in significantly en-
formed hardened rutile TiO2 coatings on Ti-6Al-4V alloys using (TO). It hanced wear resistance. This is because of the tough rutile phase oxide
was found to improve the corrosion resistance and wear of the alloys. film that forms on the surface. It improves boundary lubrication, hence
Xu et al. [225] deposited tantalum oxide layers on titanium substrates decreasing the wear rate [228]. Molybdenum is used to improve the
using polymer-assisted deposition (PAD) technique. As a result, the wear resistance of titanium alloys. Guo et al. [229] produced modified
corrosion resistance of titanium substrates improved. Surface mor- Mo layers on the surface of Ti-5Zr-3Sn-5Mo-15N. This resulted in a
phology also affects the corrosion resistance of an implant. To study this lower coefficient of friction and enhanced corrosion resistance. A study
effect four groups of samples (smooth surface (P), microstructure sur- by McKellop and Rostlund [230] showed that abrasive wear resistance
face (M), micro/nanostructure surface (MN) and functionalized micro/ of Ti-6Al-4V can be improved by nitrogen ion implantation. Processing
nanostructure surface (Ag-PDA)) were prepared. Their corrosion be- routes also influence hardness, wear friction of an implant. It was re-
havior was studied in Ringer's solution. Corrosion resistance was dif- ported by Bartolomeu et al. [231] that Ti-6Al-4V produced by SLM
ferent for the four samples: Ag-PDA > MN > P > M; Ag-PDA dis- displayed higher wear resistance. In order to study the effect of nitrogen
played the highest corrosion resistance [226]. Mokgalaka et al. [227] ions on the wear behavior, Li et al. [232] implanted nitrogen ions on
formed NiTi intermetallic coatings on the surface of Ti-6Al-4V using the surface of pure titanium, Ti-6Al-4V and Ti-6Al-7Nb. Plasma im-
laser metal deposition (LMD) process in order to improve the corrosion mersion ion implantation technique was used. This increased the
855
hardness as well as the resistance against the torsional fretting wear. avoiding bacterial adhesion have also been used: creating a polymer
With the increase in ion implantation dose wear resistance further layer (e.g. dextran [248] and poly(methacrylic acid) (PMAA)-silk co-
improved. Ti-Nb-Zr-Ta alloys have received a lot of attention because of polymer [249]), introducing tantalum oxide coatings [250] and fabri-
their lower Young's modulus and better corrosion resistance than Ti- cating titanium dioxide nanotube arrays [251] on a titanium substrate.
6Al-4V but they possess poor wear resistance. Chan et al. [233] used Laser treatment can also be used to improve the antibacterial properties
laser treatment to improve the wear resistance of Ti-35.3Nb-7.3Zr- of the implants. Chan et al. [252] studied the influence of laser surface
5.7Ta alloy. Wear and corrosion resistance were tested for the sample treatment on enhancing the antibacterial activity of titanium implants.
placed in Hank's solution. The laser treated samples showed higher This treatment resulted in a notable decrease in the bacterial adhesion.
open-circuit potential and lower current density hence, better corrosion Reduced hydrophobicity, thicker and stable oxide films and the nano-
resistance. features can be considered responsible for this type of behavior. A re-
cent (2018) review by Spriano et al. covers various strategies used to
2.8. Implant failures and their surface treatments make the Ti surfaces bioactive and anti-bacterial at the same time
[253].
Studies on dental implants and hip joint replacements have found Osseointegration is also important to minimise the chances of im-
that the probability of implant failure is around 5–20% [234,235]. Poor plant failure. Different techniques have been employed to ensure the
early bone healing at the implant-bone interface is considered to be one formation of a secure contact between the bone and implant.
of the prime reasons for implant failure post-surgery [236,237]. Post Covarrubias et al. [254] fabricated a nanoporous silica coating loaded
surgery factors like bacterial infection and excessive reactive oxygen with bioactive glass nanoparticles on titanium surface and found that
species (ROS) production can result in this improper bone healing. this accelerates apatite formation. This speeds up the formation of bone
Attempts have been made to minimise these complications by surface tissue close to the implant after 3 weeks of exposure. Also in order to
modification of the implants. Chen et al. [238] formed a multilayered improve upon osseointegration and stress shielding, porous titanium
structure made up of chitosan-catechol (ChieC), gelatin (Gel) and HA alloys are being coated with bioactive materials. Domínguez-Trujillo
nanofibers on Ti substrates. The multilayered system resulted in pro- et al. [255,256] have used porous titanium substrates and applied
tection of the cells against oxidative stress damage caused by ROS. It bioglass and HAP coatings on its surface. As a result of the pores, it
was found Chi-C multilayered implant can result in enhanced bone becomes easy for the HAP to infiltrate and result in good bone in-
healing. Ueno et al. [239] studied the influence of UV-pretreatment on growth. It has also been reported that nano-HAP coated Ti–13Nb–11Zr
the ROS production in case of CP-Ti implants. It was found that ROS alloy result in increased osteoblast adhesion [257]. Surface wettability
production was reduced by 40–50% by UV pre-treatment of the im- is another property that can influence the rate of osseointegration
plant. This could be because UV treatment enhances the hydrophilicity [258]. In the case of biomaterials, surface wettability is mostly assessed
and removes hydrocarbons deposited on the implant surface. by measuring the contact angles (CA). A high value of CA indicates low
A number of techniques have been used to prevent bacterial at- wettability or hydrophobic nature and a low CA signifies high wett-
tachment with the implant. Bhadra et al. [240] used chemical hydro- ability or hydrophilic surface [259]. It has been reported that hydro-
thermal treatment and high temperature for fabrication of titanium philic implant surfaces result in accelerated early osseointegration as
nanopatterned arrays on titanium surfaces. It was found that this ap- compared to hydrophobic surfaces [260,261]. Oshida et al. [262] did a
proach improved adherence of human cells to the substrate and in- comparative study to study the effect of surface texture on the wett-
creased the bactericidal properties of the surface. Zhao et al. [241] ability of CP-Ti, titanium‑aluminium‑vanadium alloy (Ti-6Al-4V), tita-
synthesized and immobilized chitosan –lauric acid conjugate on a ti- nium‑nickel alloy (TiNi), pure Ni, 316 L stainless steel, and co-
tanium substrate. Polydopamine was used as an intermediate layer. It balt‑chromium alloy (CoeCr). These materials were subjected to
was concluded that these enhance osteoblast growth and hinder bac- mechanical polishing and oxidation at 300 °C for 30 min in pure
terial adhesion. Fielding et al. [242] coated titanium substrates with oxygen. It was found that the titanium materials were covered with a
silver and strontium doped HA. This was done to enhance the anti- tetragonal type TiO2 film. 316 L stainless steel, CoeCr alloy, and pure
bacterial activity and bone formation. In another work by Yamaguchi Ni were covered by a cubic structured spinel oxide film. The tetragonal
et al. [243] gallium ions were incorporated on the surface of titanium rutile film formed on Ti-6Al-4V could be responsible for the low initial
by chemical and heat treatment. This serves a dual purpose: inhibits CA and low rate of change of CA. Whereas, the spinel oxide film on
bone resorption by forming apatite layer on the surface and displays 316 L stainless steel, CoeCr alloy could be the cause of high initial CA
antimicrobial activity by the release of gallium ions. Ordikhani and and low rate of change in CA. Different modification techniques like
Simchi [244] fabricated a chitosan-bioactive glass coating on a titanium incorporation of nanoscale TiO2 nanotube topography on the surface
substrate. Chitosan is known for its antibacterial and antimicrobial [263], chemical modification of conventional sand-blasted large grit
properties, whereas bioglass enhances osteointegration and bioactivity. and acid-etched titanium implants [264], surface adsorption of poly-
Chitosan was loaded with vancomycin which is an antibiotic. It was electrolytes like chitosan (CHI), poly(L-glutamic acid) (PGA), and poly
found that almost no bacteria survived on the coatings proving that (L-lysine) (PLL) [265] enhance the hydrophilic nature of titanium im-
these coating significantly reduced the risk of infection. Kalaivani et al. plants and hence improve osseointegration.
[245] fabricated a coating of Cu2+ doped CaSiO3 on Ti metal through Surface modifications are performed to increase the surface rough-
electrophoretic deposition technique and found that these display ness using techniques like blasting and abrading. Laser is a compara-
bioactivity and anti-bacterial properties. Janson et al. [246] used CP-Ti tively new technique which is used to modify the structure at micro-
(grade 2) discs to produce an anti-bacterial surface by soaking in 30 wt meter and nanometre level. Branemark et al. [266] tried to study the
% hydrogen peroxide held at 80 °C. The samples were then subjected to effect of site-specific surface modification of the implants using laser to
subsequent alkaline treatments in sodium hydroxide and calcium hy- improve bone formation. The implants with micro and nanoscale to-
droxide, and a final autoclaving step to achieve enhanced bioactivity pography were implanted in rabbit tibia and femur. It was concluded
and biocompatibility. Xu et al. [247] used octenidine dihydrochloride that the laser treatment improved bone-implant interface anchorage.
(OCT) to enhance the antibacterial property of CP-Ti substrates. OCT Shah et al. [267] selectively laser ablated CP-Ti implants. It resulted in
was loaded on the mesoporous silica nanoparticles (MSNs)-in- microtopography, along with a superimposed nanotexture and a thick
corporated titania coatings formed on the titanium substrates. It was oxide layer on the surface. It was concluded that laser modified surfaces
concluded that loading with OCT enhances the antibacterial efficiency improve bone bonding. It has also been found that surface roughness at
of titanium substrates (with composite coating) to a great extent micro- and nanoscale can also improve osseointegration. Gittens et al.
without compromising their cytocompatibility. Many other methods of [268] developed a surface modification method to produce nanoscale
856
features on the titanium substrates. It was concluded that this resulted their biocompatibility but still there have been few cases where allergy
in enhanced osteoblast differentiation which could enhance osseointe- could have been caused due to the release of dangerous ions into the
gration. One can say that nanophase materials are the next generation blood. As a result, efforts are being put into producing implants which
of biomaterials. These materials possess distinctive surface and me- display better biocompatibility. Also, different surface treatments are
chanical properties. Due to the presence of collagen and hydro- being used to improve the properties like wear and corrosion resistance
xylapatite, bones possess a highly nanostructured surface [269]. Also, and bone bonding in case of titanium implants.
bone formation around implants depends on the surface topography. It Different advanced processing techniques followed by proper sur-
is expected that by mimicking the surface nanoroughness of bones it is face coatings and modifications are being used to achieve the required
possible to improve properties of the implants [270,271]. A number of properties of titanium implants however, more resources and research
groups are working on producing a biologically inspired nanostructured is needed to turn the dream of developing an implant material which is
surface to replicate the environment to which the bone-forming cells tough, biocompatible, corrosion and wear resistant and has the value of
are mostly accustomed in the body. This approach, known as the bio- Young's modulus closer to that of bone, into reality.
mimetic approach presents a number of benefits: increased osteoblast
adhesion [269,272], excellent osteogenic properties [273], better os- Acknowledgement
seointegration [274] and reduced bacterial adhesion [275] in com-
parison to the conventional titanium surfaces. Further, by blending This research did not receive any specific grant from funding
nanocomponents and engineering nanocomposite-materials the me- agencies in the public, commercial, or not-for-profit sectors.
chanical properties can be enhanced to a greater extent as compared to
the microscopic and macroscopic materials [276]. References
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Materials Science & Engineering C: Review

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Materials Science & Engineering C 102 (2019) 844–862

Contents lists available at ScienceDirect

Materials Science & Engineering C

Review on titanium and titanium based alloys as biomaterials for T

1. Introduction taking place are summarized in Table 1.

Bone (cortical) 70–150 30–70 15–30 [43]

in various orthopaedic applications like fracture ﬁxation, hip joint re-

Fig. 3. Crystal structure of TiO2 a) rutile b) anatase c) brookite [58].

like alpha structure is formed whereas an intermediate cooling rate

Ti-6Al-4V Standard 110 930 860 [45]

coatings, electrochemical deposition, plasma spraying and sputter

264–271. Appl. Surf. Sci. 367 (2016) 80–90.

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