Accepted Manuscript

Material Processing of Hydroxyapatite and Titanium Alloy (HA/Ti) Composite

as Implant Materials Using Powder Metallurgy: a Review

Amir Arifin, Abu Bakar Sulong, Norhamidi Muhamad, Junaidi Syarif, Mohd
Ikram Ramli

PII: S0261-3069(13)00897-2
DOI: http://dx.doi.org/10.1016/j.matdes.2013.09.045
Reference: JMAD 5876

To appear in: Materials and Design

Received Date: 24 July 2013

Accepted Date: 17 September 2013

Please cite this article as: Arifin, A., Sulong, A.B., Muhamad, N., Syarif, J., Ramli, M.I., Material Processing of
Hydroxyapatite and Titanium Alloy (HA/Ti) Composite as Implant Materials Using Powder Metallurgy: a Review,
Materials and Design (2013), doi: http://dx.doi.org/10.1016/j.matdes.2013.09.045

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Material Processing of Hydroxyapatite and Titanium Alloy (HA/Ti) Composite as Implant

Materials Using Powder Metallurgy: a Review

Amir Arifin1,2, Abu Bakar Sulong1, Norhamidi Muhamad1, Junaidi Syarif1, Mohd Ikram Ramli1

1
Department of Mechanical and Material Engineering, Universiti Kebangsaan Malaysia,
43600 Bangi, Selangor, Malaysia.
2
Department of Mechanical Engineering, Sriwijaya University,30662 Indralaya,
Sumatera Selatan, Indonesia

Abstract

The bio-active and biodegradable properties of hydroxyapatite (HA) make this material a

preferred candidate for implants such as bone replacement in replacing natural tissues damaged

by diseases and accidents. However, the low mechanical strength of HA hinders its application.

Combining HA with a biocompatible material with a higher mechanical strength, such as a

titanium (Ti) alloy, to form a composite has been of interest to researchers. A HA/Ti composite

would possess characteristics essential to modern implant materials, such as bio-inertness, a low

Young’s modulus, and high biocompatibility. However, there are issues in the material

processing, such as the rheological behavior, stress-shielding, diffusion mechanism and

compatibility between the two phases. This paper reviews the HA and Ti alloy interactions under

various conditions, in vitro and in vivo tests for HA/Ti composites, and common powder

metallurgy processes for HA/Ti composites (e.g., pressing and sintering, isostatic pressing,

plasma spraying, and metal injection molding).

Keywords: Ceramic-metal composite, powder metallurgy, material processing, biocompatibility,

mechanical properties

1
* Corresponding author. Tel.: +603-89216678; Fax: +603-89259659

E-mail address: abubakar@eng.ukm.my

1. Introduction

The rapid growth of the global population is leading to an increased demand for implants for

bone dysfunction caused by diseases such as arthritis and cancer [1]. Such implants are necessary

to repair or alter natural body tissues [2]. However, given the unique structures and mechanical

properties of natural tissues such as bone tissue, repairing or changing them is challenging. Since

the introduction of bioceramics as medical implants in the 1960s, metal implants such as

titanium alloy, stainless steel, and cobalt-chromium alloys have been extensively used in medical

applications [3]. In the early period of medical implant development, the only criteria for implant

material suitability were appropriate physical properties and non-toxicity [4]. Today, the criteria

include the physical properties of the bone implant material and its ability to promote the growth

of body tissue [5]. Metal-based implants have a higher Young’s modulus than bones, which

leads to stress shielding. Metal implants also have poor biocompatibility, which is necessary to

promote the growth of natural tissue. However, metal-based implants have the beneficial

mechanical properties of strength and corrosion resistance. Hydroxyapatite (HA) is a bioceramic

material with poor mechanical properties, especially for load-bearing applications. However, HA

has a similar structure to bones and can promote the growth of natural tissues. Combining a

titanium alloy with HA creates a new biomaterial with excellent mechanical and biological

properties. Thus, research on this material and its preparation process has been conducted [6-10].

2
This paper aims to review the interaction between titanium alloys and HA as a medical implant

composite. Common methods of combining HA and titanium are also discussed.

2. Criteria for Biomaterials Applications

In the early period of implant material development, a material was considered suitable to

replace natural tissue when it had minimal or zero toxicity [11]. Later on, the ability to promote

natural tissue growth was considered. Several studies have been conducted to achieve this goal in

terms of the processing route, design and material modification [12-18]. Biomaterials for

implants should not be cytotoxic. Cytotoxicity is caused by increased metallic ion content in the

blood. Thus, biocompatibility itself can be translated simply as “do no harm” to the body and due

to encourage healing [19]. The roughness of an implant surface is conducive to the bonding

between implant materials and tissues [20]. Porous structures and rough surfaces are necessary

for facilitating bone ingrowth and osteointegration [11, 21-23]. Rough surfaces and porous

structure able to control by its processing condition [24-29].

Stress shielding is a common problem of biomaterials [30, 31]. This phenomenon arises

when the Young’s moduli of bones (Fig.1) and the implant material are different, which causes

bone resorption. Most biomaterials based on metals and ceramics have higher Young’s moduli

than cortical and trabecular bones [32, 33] (Table 1). Material selection and manufacturing

processes have been performed to address this problem. Titanium alloys are potential implant

materials because their Young’s moduli are closer to that of bone (10–30GPa) compared to other

metal implants [34]. Another approach involves controlling the Young’s modulus of bone by

modifying its porosity [35].

3
 (Insert Fig. 1. Stress shielding mechanism [36])

3. Titanium and Titanium Alloys

Since the mid-1940s, titanium and its alloys have been widely used for medical applications,

aerospace structures, and chemical industries [37, 38]. Many researchers continue to develop

titanium alloys for medical applications because of their unique properties, such as high specific

strength, lightweightness and bioinertness [1, 39-41]. Titanium and its alloys are classified as

light materials with adequately high specific strength in engineering structures (Fig. 1). Titanium

has a density of 4.5 g/cm3 and a melting point of 1668 °C. Titanium alloy has a tensile strength

of approximately 1400 MPa at room temperature. At high temperatures, titanium becomes

reactive with other materials. Meanwhile, titanium alloys have high corrosion resistance at room

temperature because of the good biocompatibility and stable passivity of their surface oxide

films [6]. Titanium alloys can be divided into α-, (α + β)-, and β-type alloys. β-type alloys have

the lowest Young’s modulus (Table1), which is closest to the Young’s modulus of bone (10–30

GPa) [42].

(Insert Fig. 2. Density of selected materials [43].)

(Insert Table 1. Comparison of the mechanical properties of implant materials [43])

4. Hydroxyapatite

Hydroxyapatite theoretically exists as the hydroxyl end-member of apatite, which was suggested

in 1912 [44]. Hydroxyapatite is one of the apatite structures that were observed in rock, the

4
apatite structure has the basic formula Ca10(PO4)6X2. X in the formula is the representation group

member of apatite and refers to a hydroxyl (OH) group for hydroxyapatite, a fluoride (F) group

for fluorapatite, and a chloride (Cl) group for chlorapatite [45]. Synthetic HA is widely applied

as a substitute for the hard tissues of the human body damaged by disease or accident. HA as an

implant can bond and promote natural tissue growth because of its chemical similarity to bone

mineral [46-49]. At high temperatures, HA undergoes decomposition, which starts with

dehydroxylation at approximately 900°C in air and at 850°C in a water-free atmosphere. The

next stage is decomposition, which produces tetra calcium phosphate (TTCP) and tri calcium

phosphate (TCP). TCP consists of β-TCP at <1200 °C and α-TCP at >1200 °C. HA loses many

hydroxyl groups above 1300 °C and thus loses significant weight [45]. Other studies have

revealed that at >1350 °C, the strength of HA drastically decreases [46].

5. Porous Structure

A porous structure in an implant material has the function not only to decreasing the Young’s

modulus of the material implant [50] but also of facilitating osteointegration. Moreover,

characteristics of the porous structure play an essential role in the regeneration of bone [51-53].

Porous structures can be divided into open or closed cells. In an open cell condition, each cell in

the structure has a connection. In a closed cell, no connection exists between cells on the

structure [54]. The interconnection of each cell is critical for allowing blood and nutrition into

the structure to encourage bone ingrowth and osteointegration. The pore size depends on the

application and thus has no standard size. For bone ingrowth, the minimum pore size is 50 µm.

Large pores tend to be drained of blood and nutrient more than small pores. Thus, the pore size

5
must be considered when examining the mechanical properties of an implant [51, 55]. Powder

metallurgy (PM) processes can be used to produce combined small and large pores by adjusting

the powder size, pressure, sintering temperature, and method of adding the powder to the space

holder [35, 50, 56-58].

6. Interaction of Titanium Alloys and Hydroxyapatite

The interaction between titanium alloys and hydroxyapatite has been studied by several

researchers [6, 35, 59-65]. Thermal stability has been observed to affect the synthesis of HA

[45], such that in the thermal processing of a HA/Ti system, TCP and TTCP are commonly

produced after dehydroxylation and decomposition [66].

6.1 Argon environment

As previously discussed, dehydroxylation begins at approximately 900 °C in air and at 850 °C in

a water-free atmosphere. Pure HA is stable up to 1200 °C under an argon atmosphere. However,

in HA/Ti composites, Ti ions react with the dehydrated water of HA to yield titanium oxide,

thereby accelerating the dehydroxylation and decomposition of HA at approximately 800 °C.

CaO and TTCP are the main products of HA decomposition in a Ti/HA system with increased

sintering temperature. TTCP then decomposes to CaO at >1200 °C such that only two phases are

formed, namely, CaO and an amorphous phase [64]. Balbinotti et al. reported that at

approximately 1026 °C under an argon atmosphere, calcium titanate, TixPy, and TCP phases are

the decomposition products, as observed in the XRD result in Fig. 3 [65]. These phases are

formed at the boundary that covers the titanium particles.

6
 (Insert Fig. 3. XRD pattern of Ti/10%HA composite at 1200oC for 2 hour under argon
condition [65])

6.2 Air environment

Egorov et al investigated and characterized the interactions within Ti/HA composites in air at

700–1200 °C and observed that titanium is oxidized (Fig. 4) [59]. This result is supported by

other studies on extreme oxidation at 1100 °C.

(Insert Fig .4. XRD pattern of HA composite under an air environment[59])

TiO2 is produced at 800 °C, and only two crystalline phases exist: TiO2 and calcium titanate

(CaTiO3). CaTiO3 is produced by the interaction between titanium and HA [59]. Berezhnaya et

al. compared annealing results in air and argon [62]. Specimens annealed in argon have a smooth

surface, and those annealed in air have a surface covered with titanium oxide. Moreover,

Berezhnaya et al. revealed that annealing in air reduces the biocompatibility because the

optimum Ca/P ratio is not reached [45, 62]. The optimum biocompatibility of HA is achieved at

approximately 1.5–1.7Ca/P.

6.3 Vacuum environment

Yang et al. studied HA/Ti composites in a vacuum at 1100 °C, and observed the formation of

TCP, TTCP, and calcium titanium oxide (Ca2Ti2 O5) [60]. Fractured surface analysis revealed

three types of surface morphologies of the HA/Ti composite, as shown in Fig. 5. Granular

7
aggregation (calcium phosphate and Ca2Ti2O5), a porous structure, and a glassy phase are

observed in HA, and α-TCP and TTCP are present in the composite. This morphology is caused

by the unequal melting points of the two materials as well as by the fusion between HA and

molten Ti

(Insert Fig 5. Scanning electron micrograph of the fracture morphology of Ti/HA composite in a
vacuum: (a) 80% HA (1500× original magnification) and (b) 90% HA (1200× original
magnification). (A) Granular aggregation, (B) porous area, and (C) glassy phase.[60])

There is a possibility of reactions between hydroxyapatite and Ti under vacuum condition [60].

In the first stage, hydroxyapatite loses a hydroxyl chain in the following reaction:

Ca10(PO4)6(OH)2 ----(in vacuum, >800 oC)--
Ca10(PO4)6(OH)2-2x Ox+xH2O (gas)….. (1)

H2O oxidized titanium became titanium oxide (TiO2)

Ti+2H2O (gas) -
TiO2+2H2.…. (2)

CaTi2O5 was resulted from the reaction hydroxyapatite with TiO2

Ca10(PO4)6(OH)2 +2 TiO2 ---
3Ca3(PO4)2 + CaTi2O5 + H2O …. (3)

Under elevated temperature α-TCP and TTCP

Ca10(PO4)6(OH)2 ----(in vacuum, >800 oC)--
Ca4P2O9 + 2Ca3(PO4)2+ H2O …(4)

6.4 Nitrogen environment

The fabrication of a HA/Ti system in a nitrogen environment has been reported by several

researchers [67, 68]

8
 (Insert Fig. 6. XRD spectra of HA-20vol%Ti in a nitrogen environment for 60 min at (a)
1000 and (b) 1100 °C[67])

Fig. 6 shows that at 1000 °C, only a small quantities of α-Ca3(PO4)2,(α-TCP), and Ca4O(PO4)2

were detected. The decomposition phase of Ti/HA composites increase with increased sintering

temperature, and no reaction occurs between HA and titanium [67]. TCP in HA/Ti composites

degrades faster than HA, promoting new natural tissues and leading to unstable mechanical

properties of the implant for natural tissue growth [8, 67].

6.5 Diffusion mechanism between HA and Ti

At the HA/Ti interface, the Ti atoms at elevated temperature tend to oxidize to become TiO2, and

normally, the TiO2 position on top of the titanium surface; however, parameter processing tends

to alter the formation passivation of TiO2. In this situation, Ti atoms from the metallic bulk

move and inter-diffuse on the film while oxygen atoms migrate to the titanium bulk [69, 70]. The

result of this simultaneous process is titanium oxide in amorphous or crystalline form. The

oxidation kinetics of titanium is determined by the adsorption rate of oxygen, oxygen as an

interstitial atom diffuses to the Ti lattice until reaching a saturation level, followed by oxidation

of titanium. The diffusion rate of oxygen will decelerate when TiO2 occur [71]. Ye et al. and Chu

et al. also reported that dehydroxylation of hydroxyapatite would be accelerated by the presence

of Ti atoms, under this condition, oxygen diffuses to the Ti metallic bulk to form titanium oxides

[64, 67]. Furthermore, calcium and phosphorous ions diffuse into the Ti substrate to affect the

Ca/P ratio of apatite. The phosphorous ion has the ability to migrate rapidly into the Ti substrate

due to its smaller radii and lower activation energy. Other authors reported that Ca, P and Ti

have been detected on some regions but other phase that are common results of the reaction

9
between HA and TiO2 were not observed. The presence of Ca, P and Ti atoms demonstrated that

interdiffusion occurred in the HA / Ti composite [62, 70].

(Insert Fig 7. SEM image of the polished surface of a HA/Ti composite (a) polished area and

(b)EDS line scan analysis [65])

Balbinotti et al. performed EDS line scans on the polished part of a HA/Ti composite; titanium

and a small amount of calcium were detected on the polished area [65]. It was believed that the

titanium formation phase Titanium and calcium tend to be fragile and are partially lost because

of the polishing mechanism. At the HA/Ti interface, titanium and phosphorous were detected, as

observed in Fig 7. The vertical arrow indicates the area where phosphorus was detected; under

this condition, Ti and P were detected in the formation TixPy phase which demonstrates that the

phosphorus ion has diffused to the titanium ion during sintering. Commonly, differences in the

thermal expansion of ceramic will lead to cracking due to non uniform of residual stresses in the

material [72]. Cracks have also been observed in HA / Ti composites that will degrade their

mechanical properties. Shi et al. observed micro cracks in the HA/Ti composites, which were

thought to be due to differences in the thermal expansion of Ti and HA [69]. Moreover, in

addition, micro cracks were also found in the results using MIM products as reported by Thian et

al. [63].

10
7. Nanostructure of HA/Ti system

Nanomaterials are known as great potential candidates for implant material application [73];

Webster at al , reported that nanostructure materials (with grain sizes less than 100 nm ) have the

ability to increase function osteoblast adhesion, which supports the next stage of tissue growth

[27, 29, 74], as shown on the Fig.8. Others researchers also reported that nanoscale topography

played a critical role in increasing cell activity, which rapidly encouraged tissue growth

compared with conventional materials [75-77]. The fabrication of HA/Ti composites on the

nanoscale have the advantage of increasing consolidation between Ti and HA such as the

hardness value, young’s modulus and corrosion resistance [14, 78]. The combination of

mechanical alloying and the powder metallurgical process has been proposed by Niespodziana et

al. in the fabrication of nanostructure HA/Ti [78]. A unique method has been proposed by

Farnoush et al, these researchers have combined friction stir processing and electrophoretic

deposition to fabricate nanostructure HA/Ti [79].

(Insert Fig. 8. Nanophase materials promote greater amounts of protein adsorption and
encourage additional new bone formation compared with conventional materials [73].)

8. in vitro and in vivo Test

Tests of biological properties are important in the manufacture of implant materials [8]. These

tests determine the suitability of an implant material. In vivo and in vitro tests are extensively

used for biological evaluation. In vivo or “in the living organism” tests are performed inside the

body of a living organism, and in vitro or “in glass” tests are performed in inanimate laboratory

equipment[80]. The biocompatibility of a material is tested in vitro by immersing a specimen for

a few weeks in simulated body fluid (SBF) whose conditions are similar to those in human blood

11
plasma [81]. The ion concentrations in SBF and human blood plasma are listed in Table 2. Thian

et al. reported that HA/Ti composites are tested through immersion in SBF solution to induce

complete dissolution of the secondary phase after 2 weeks [8, 81]. Complete dissolution of the

calcium phosphate phase occurs during the initial stage of immersion, which results in the

deterioration of the mechanical properties of the specimen. In the next stage, the mechanical

properties of the HA/Ti composites significantly increases because of the precipitation of the

apatite layer [8]. The combination of titanium and HA promotes apatite nucleation. In the

secondary phase, Ti2O helps generate apatite on the composite surface [82, 83]. In addition, the

dissolution of CaO encourages a constructive location for apatite nucleation and growth [82].

(Insert Table.2. Concentration of ion Simulated body fluid (SBF) and human blood plasma
[81])

In vivo tests of a HA/Ti composite have been conducted by Chu et al.[66, 68]. using New

Zealand white rabbits. These researchers cut the implant model into rectangular shapes 3.3 mm

wide, 3.3 mm thick, and 5–6 mm long rectangular shapes, as illustrated in Fig. 9.

(Insert Fig. 9. Implant model of a HA/Ti composite: a) rectangular specimen and b) cross-
sectional view of specimen (DB = defective bone region; region for bone healing area) [66])

In vivo tests revealed that the HA/Ti composite has excellent biocompatibility that enables it to

integrate with bone, which increases osteointegration and bonding strength with time after the

initial stage of implantation [66, 68, 84]. According to Congqin Ning and Yu Zhou, HA/Ti

composites produce a bone-bonding interface with bone through an apatite layer. The bioactivity

12
value of HA/Ti compositesis determined by increasing the titanium content in a HA/Ti system

[85]. These researchers also revealed that the in vivo and in vitro tests have similar results as

confirmed by in vivo and in vitroinvestigations performed on other materials [86].

9. Powder Metallurgy

PM is a manufacturing method in which powder metals are compressed with or without other

materials, and then heated without a melting stage for solidification and strengthening [87]. PM

produces excellent microstructures and compositions for manufacturing near-net-shaped

products [88]. Several methods have been proposed to produce HA/Ti composites, such as

conventional PM [61, 65, 89], non-conventional PM [90], and plasma spraying [91-93]. The

conventional method or “pressing and sintering process” usually consists of mixing the powder,

compacting the powder in a desired mold, and sintering [94]. Occasionally, during the

compaction step, the mold temperature is raised to high temperatures and is classified as hot

pressing [66, 68]. Non-conventional processes include powder injection molding (PIM) and

isostatic pressing, which can be further divided into hot and cold processes [94].

9.1 Pressing and sintering

Mixing is commonly required in PM and involves mixing the powder with other powders as well

as with a binder. Failure in mixing irreversibly affects the next step. The mixing stage involves

numerous parameters such as mixing time, mixing temperature, powder size, and powder shape,

composition of powder, and composition of the binder [95]. Thian et al. proposed the ceramic

slurry approach for applying PIM and hot/cold isostatic pressure. Ti6Al4V and HA powder were

mixed with polyvinyl alcohol (PVA) as a binder for a certain time [96]. To remove the binder,

the Ti6Al4V slurry was heated at 450 °C in air and the consolidation stage was performed at

13
higher temperatures (~600–700 °C). Using this method, HA can be coated around the titanium

core as shown in Fig. 10.

(Insert Fig. 10. Scanning electron micrograph of HA/Ti6Al4V composite powder using the
ceramic slurry approach [96])

In conventional PM, uniaxial pressure is applied when the pressing powder is contained in a die.

Removal of powder from the die can only be performed through the in-line movement of a punch

from a no-cross-equipment mechanism [94]. Therefore, a complex geometry cannot be produced

using this method. Moreover, the density of green compacts through conventional PM varies.

However, despite these limitations, PM has numerous advantages such as low manufacturing

cost, high tolerance, and minimal secondary machining process requirements.

9.2 Isostatic pressing

Isostatic pressing is one well-known near-net-shape methods to produce parts with highly

complex shapes [97]. Unlike conventional PM which uses uniaxial pressure, isostatic pressing

powder makes use of a flexible mold “enveloped”-contained powder with applied pressure

through hydraulic pressure from all directions as shown in Fig.11 [98]. Isostatic pressing can be

divided into hot and cold types, wherein cold isostatic pressing operates at room temperature

using water and oil as the fluid pressure. In contrast, hot isostatic pressing operates at elevated

temperature [94].

(Insert Fig.11. Illustration of flexible mold movement in the isostatic pressing process[98])

14
Isostatic pressing is performed to induce maximum density [99]. In hot isostatic pressing, some

parameters such as the sintering temperature and pressure can be controlled to produce

interconnected porosity, good mechanical properties, and high permeability [100]. The resulting

complete diffusion bond is one of the main advantages of this method. The complexity of the

inner and outer surfaces of the product must be overcome to avoid the negative effects of the

large product size [97]. Under correct design and control, the mechanical properties of the

product of hot isostatic pressing, i.e.,near-wrought materials, significantly improve [97, 101].

Hot isostatic pressing requires necessary precision control for every stage to achieve optimum

results. Therange time per cycle is counted in hours to produce a specific component. However,

producing many parts in one batch can decrease the running cycle. Sometimes, a product

requires a high cooling rate to change its microstructure and mechanical properties. Thus,

conventional hot isostatic pressing is the common option [97]. At high temperatures, HA

decomposes into a secondary phase [45], especially when the plasma-spraying method is used.

Onoki and Hashida proposed a route to avoid this problem. These researchers used hot isostatic

pressing to coat HA on titanium bars at low temperatures through the double-layered capsule

hydrothermal hot-pressing method under hydrothermal isostatic pressure (Fig. 12) [102]. They

successfully coated HA on titanium bars at 135 °C .

(Insert Fig. 12. Cross section of the double layered capsule hydrothermal hot-pressing method
[102])

15
9.3 Plasma spray

Surface modification through plasma spraying may improve the biocompatibility and mechanical

properties of metal implants [93]. Plasma spraying coats a material with other materials

possessing specific properties (Fig.13). For example, HA is used as a coating material and

titanium alloy is used as a substrate. Metal implants with low biocompatibility are usually coated

with a material of higher biocompatibility [91].

(Insert Fig. 13. Illustration of plasma spray process [103])

The structural integrity of bonds between a substrate and coating under fatigue is determined by

the suitability of the chemical and thermal properties. To avoid mismatches between a substrate

and coating, an intermediate layer is used between them [104, 105]. The mechanism of bonding

between HA and titanium through plasma spraying that utilizes CaTiO3as a bond layer is

stronger than the bonding mechanism through mechanical interlocking. HA reacts with TiO2 at

800–1000°C on the Ti surface, where CaTiO3 and TCP are present as secondary phases [91].

Forming composite coatings with Ti increases the strength of the adhesive bonding coating.

Consequently, Ti and HA can uniformly spread on the surface. A SBF testing also indicates no

reduction in the bioactivity of a material [106]. The plasma-spraying method is known as an

easy and safe method to coat HA onto Ti alloys. However, in biomedical applications, problems

involving residual stress, a low level of crystallinity, a low level of porosity, and non-uniform

distribution porosity are encountered [107, 108] Microporosity includes sizes of approximately

10–300 nm caused by a significant decrease in the mechanical properties of a material [109].

Combining plasma spraying and isostatic pressing has been proposed by certain researchers to

16
address this problem. Satisfactory results have been obtained in decreasing the microporosity and

improving the mechanical properties of a material [109, 110].

9.4 Metal injection molding

MIM is commonly used after modification and innovation at each stage of PIM [111], as shown

in Fig. 14. PIM itself is a combination of two methods: plastic injection molding and PM [95]. In

MIM, the volume fraction of plastic for PIM is substituted by metal powder, which is mixed with

plastic into pasta (feedstock). The feedstock is injected into the molding machine (green part),

followed by an extraction binder and finally by sintering [112] If a material used is ceramic, it

is called ceramic injection molding, whereas MIM denotes covering materials and ceramics

[95]. The metal injection process offers reduced production costs, especially in producing

complex components in large quantities [113, 114]. In titanium processing using MIM, the small

and complex products are contaminated by carbon, oxygen, and nitrogen, which affects the other

processes [115]. Contamination occurs in oxide form at the interface of a particle that initiates

cracking. The contamination level of a material contributes to the fatigue properties of a product

[116].

(Insert Fig.14. Stages of the metal injection process [111])

MIM is used to fabricate biomaterial components [8, 12, 113, 117]. Developing composite

structures containing titanium alloys and HA for medical applications using MIM has been

extensively studied by Thian et al. [8, 63, 90, 118]. HA/ Ti composite powder is prepared

through the ceramic slurry approach with PVA as a binder. PVA is removed from the

homogenized composite powder by heating. The powder is then crushed into small particles

17
using a mortar and pestle [119]. The composite powder is mixed with commercial a multi-

component binder system consisting of natural wax, fatty acid wax, stearic acid, poly-oxi-

alkylen-ether, and olefin-hydrocarbons. A sigma blade mixer is used to mix feedstock consisting

of HA/Ti6Al4V composite powder and binder at a mixing temperature of 90 °C until

homogeneity is achieved. The mixing temperature is determined by differential scanning

calorimetry [118]. For 50 wt% Ti6Al4V and 50 wt% HA, Thian et al. found that a powder

loading of 60 vol% is the most suitable for yielding homogeneous and moldable feedstock [90].

The effects of the sintering temperature, heating rate, and cooling rate on the density and

porosity are determined. At a sintering temperature of 1100 °C, the density, hardness, flexural

strength, and flexural modulus increase at heating rate of 7.5 °C/min and cooling rate of 5

°C/min with a high flexural strength and modulus at 1150 °C [63].

At high sintering temperatures, a HA/Ti system decomposes at 800 °C [46, 60]. Ye et al [64]

found that the presence of titanium in HA accelerates the dehydroxylation and decomposition of

HA. The decomposition of HA increases with increased sintering temperature, and significant

decomposition begins after the specimens are sintered above 1100 °C [63]. In vitro experiments

on HA/Ti specimens have revealed their chemical content and surface morphology after

immersion in SBF. After 2 weeks, the dissolution of secondary phases such as TCP, TTCP, and

CaO is complete. At 2–4 weeks, the mechanical properties of the specimens decrease because of

the dissolution of calcium phosphate layers. Afterwards, the mechanical properties are recovered

by the precipitation of the apatite layer[8]. Some methods of fabricating HA/Ti composites that

approach the mechanical properties of bone and have Young’s modules ranging from 10 GPa to

30 GPa have been proposed, as shown in (Table 3). However, the manufacturing cost, size, and

geometry of the products must still be considered.

18
 (Insert Table.3 Mechanical properties of HA/Ti composites based on various processes)

In the early weeks of in vitro tests, the dissolution of HA/Ti composites generally produce

secondary phases such as TCP, TTCP, and CaO. The mechanical properties of implants

significantly decrease and the mechanical properties increase to achieve the near-initial value

after the next stage [8].

10. Conclusions

Issues concerning the material processing and metallurgy characteristics have been reviewed and

discussed to meet the requirements for medical implant applications using existing

manufacturing process. The composition of titanium and HA determines the effectiveness of the

mechanical properties and biocompatibility of HA/Ti composites. Moreover, the sintering

parameters are critical factors in determining the phase of two materials formed during the

diffusion process. In particular, the sintering temperature plays a dominant role in the fabrication

of HA/Ti composites because this parameter affects the thermal stability of HA. Generally,

HA/Ti composites produce TCP, TTCP, and CaO in air, with the main phases being TiO2 and

calcium titanate. in vivo and in vitro tests validate the ability of HA/Ti composites to form bonds

with natural tissues, especially at the early stages of implantation. In conclusion, optimization of

process parameters especially during sintering parameters (temperature, heating rate, time, gas

condition) should be further investigated to determine a better working processing window for

the manufacturing of HA/Ti composites.

19
Acknowledgements

This work was supported by grant No. UKM-DLP-2012-027 from the Universiti Kebangsaan

Malaysia’s Research University Grant and FRGS/1/2011/TK/UKM/02/20 from the Malaysia

Ministry of Higher Education (MOHE).

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List of Table

Table 1. Comparison of the mechanical properties of implant materials [43]

Table. 2. Concentration of ion Simulated body fluid (SBF) and human blood plasma [81]

Table. 3 Mechanical properties of HA/Ti composites based on various processes

Figure Caption

Fig. 1. Stress shielding mechanism [36]

Fig. 2. Density of selected materials [43].

Fig. 3. XRD pattern of Ti/10%HA composite at 1200oC for 2 hour under argon condition [65]

Fig .4. XRD pattern of HA composite under an air environment [59]

Fig. 5. Scanning electron micrograph of the fracture morphology of Ti/HA composite in a

vacuum: (a) 80% HA (1500× original magnification) and (b) 90% HA (1200× original
magnification). (A) Granular aggregation, (B) porous area, and (C) glassy phase.[60]
26
Fig. 6. XRD spectra of HA-20vol%Ti in a nitrogen environment for 60 min at (a) 1000 and (b)
1100 °C [67]

Fig 7. SEM image of the polished surface of a HA/Ti composite (a) polished area and (b)EDS
line scan analysis [65]

Fig. 8. Nanophase materials promote greater amounts of protein adsorption and encourage
additional new bone formation compared with conventional materials [73].

Fig. 9. Implant model of a HA/Ti composite: a) rectangular specimen and b) cross-sectional view
of specimen (DB = defective bone region; region for bone healing area) [66]

Fig. 10. Scanning electron micrograph of HA/Ti6Al4V composite powder using the ceramic
slurry approach [96]

Fig.11. Illustration of flexible mold movement in the isostatic pressing process [98]

Fig. 12. Cross section of the double layered capsule hydrothermal hot-pressing method [102]

Fig. 13. Illustration of plasma spray process [103]

Fig.14. Stages of the metal injection process [111]

27
Fig. 1. Stress shielding mechanism [36]

Fig. 2. Density of selected materials [43].

28
Fig. 3. XRD pattern of Ti/10%HA composite at 1200oC for 2 hour under argon condition [65]

Fig .4. XRD pattern of HA composite under an air environment [59]

29
Fig. 5. Scanning electron micrograph of the fracture morphology of Ti/HA composite in a
vacuum: (a) 80% HA (1500× original magnification) and (b) 90% HA (1200× original
magnification). (A) Granular aggregation, (B) porous area, and (C) glassy phase.[60]

Fig. 6. XRD spectra of HA-20vol%Ti in a nitrogen environment for 60 min at (a) 1000 and (b)
1100 °C [67]

30
Fig 7. SEM image of the polished surface of a HA/Ti composite (a) polished area and (b)EDS
line scan analysis [65]

Fig. 8. Nanophase materials promote greater amounts of protein adsorption and encourage
additional new bone formation compared with conventional materials [73].

31
Fig. 9. Implant model of a HA/Ti composite: a) rectangular specimen and b) cross-sectional view
of specimen (DB = defective bone region; region for bone healing area) [66]

Fig. 10. Scanning electron micrograph of HA/Ti6Al4V composite powder using the ceramic
slurry approach [96]

32
Fig.11. Illustration of flexible mold movement in the isostatic pressing process [98]

Fig. 12. Cross section of the double layered capsule hydrothermal hot-pressing method [102]

33
Fig. 13. Illustration of plasma spray process [103]

34
Fig.14. Stages of the metal injection process [111]

35
Table 1. Comparison of the mechanical properties of implant materials [43]

E(GPa) YS (MPa) σf(MPa) %EL BF.10-3

FeCrNiMo (316L) 210 450 250 40 1.2
CoCr (as cast) 200 500 300 8 1.5
CoNiCr (as wrought) 220 850 500 20 2.3
TiAl6VA 105 900 550 13 5.2
TiAl5Fe2.5 105 900 550 15 5.2
cp-Ti 100 300 200 40 1.8
cp-Ta 200 300 200 40 1.3
cp-Nb 120 250 150 70 1.3
YS= Yield strength, E= Young’s modulus, σf =Fatigue strength, BF=Biofunctionality = σf/E, %EL= Elongation

Table. 2. Concentration of ion Simulated body fluid (SBF) and human blood plasma [81]

Species Ion concentration (mmol/l)

Blood plasma SBF
Ca2+ 2.5 2.2
HPO2-4 1.0 0.8
Na+ 142.0 140.3
Cl- 148.8 148.0
Mg2+ 1.5 1.3
K+ 5.0 5.3
SO2-4 0.5 0.5
HCO-3 4.2 4.0

36
Table.3 Mechanical properties of HA/Ti composites based on various processes

Process Sintering Composition E(GPa) HV σ(MPa)

Temp (oC)
Press and 1300 HA (BHA & EHA) + ~22-30 GPa 166.4- 50.47-53.29 [57]
Sinter Process Ti ( 5-10 wt %) 235.44
Hot-pressing 1100 Ti-20 vol% HA 102.6 3.41 GPa 170.1 [62]
Hot-pressing 1100 HA-20 vol%Ti 75.91 3.13 GPa 78.59 [63]
Hot-pressing 1100 HA-40 vo%Ti 79.31 2.94 GPa 92.1 [64]
Plasma-spray - HA & Ti - 384 28.6[88]

Plasma-spray - 50 wt% HA/50 wt% ~37 ~310 [76]

(after in vitro (after In
test) vitro test)
Metal Injection 1050-1150 50 wt% HA/50 wt% ~22.5 GPa ~1.20- ~15.9 [59]
Molding 1.26 GPa

Metal Injection 1050-1150 50 wt% HA/50 wt% ~ 17.7-20 - 23.5-25.8 (after

Molding GPa (after In in vitro test)[8]
vitro test)
E= Young’s modulus, σ = Bending strength, HV =Vickers hardness

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Highlights

• Review on physical and chemical interaction of Ti-HA at processing steps.

• Critical criteria to be biomaterial are been summarized.
• Critical issues in fabrication methods of Ti-HA composites.
• Advantages and disadvantages of those fabrication methods.

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