J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/jmbbm

Research paper

Ti–Nb–Sn–hydroxyapatite composites synthesized bymechanical alloying and high frequency induction heatedsintering

Wang Xiaopenga,∗, Chen Yuyonga, Xu LiJuana, Xiao Shulonga, Kong Fantaoa,Kee Do Woob

aNational Key Laboratory of Science and Technology on Precision Heat Processing of Metals, Harbin Institute of Technology,Harbin 150001, ChinabDivision of Advanced Material Engineering and Research Center of Advanced Materials Technology, Chonbuk National University,Chonbuk 561-756, Republic of Korea

A R T I C L E I N F O

Article history:

Received 30 April 2011

Received in revised form

8 July 2011

Accepted 10 July 2011

Published online 21 July 2011

Keywords:

Microstructure

Compression properties

Ti-based composite

Mechanical milling

Cell culture

A B S T R A C T

A β-type Ti-based composite, Ti–35Nb–2.5Sn–15–hydroxyapatite (HA), has been synthesized

by mechanical alloying and powder metallurgy. The effects of milling time on

microstructure, mechanical properties and biocompatibility of the sintered composites

were investigated by scanning electronic microscopy (SEM), X-ray diffraction (XRD),

microhardness tests, compression tests and cells culture. The results revealed whenmilling

time increased, the homogeneity and relative density of the sintered composite increased,

but the finished sintering temperature decreased. The compression Young’s modulus of

sintered composite from 12 h milled powders was about 22 GPa and its compression

strength was 877 MPa. The cell culture results indicated cell viability for these sintered

composites was very good. These results revealed the Ti–35Nb–2.5Sn–15HA composite

could be useful for medical implants.c⃝ 2011 Elsevier Ltd. All rights reserved.

2

d

1. Introduction

Ti and Ti-based alloys such as Ti–6Al–4V have been widelyused for biomaterials because of their better mechanicalproperties and corrosion resistance compared with stain-less steels and Co–Cr alloys (Long and Rack, 1998; Taddeiet al., 2004). But the Young’s modulus of Ti–6Al–4V ELI al-loys (110 GPa) was much higher than that of human bone(10–30 GPa). The Young’s modulus mismatch would cause

∗ Corresponding author. Tel.: +86 451 86418802; fax: +86 451 8641880E-mail address: hitwangmiles@gmail.com (X. Wang).

1751-6161/$ - see front matter c⃝ 2011 Elsevier Ltd. All rights reservedoi:10.1016/j.jmbbm.2011.07.006

.

bone loss, implant loosening and premature failure of theartificial hip (Zhou et al., 2004; Zhu et al., 2008; Niinomi,2008). Therefore, an important requirement of biomaterialsis a modulus close to that of natural bones. Steinemann andKawahara studied the cytotoxicity and biocompatibility ofpure metals and some metallic biomedical alloys. Accord-ing to their reports elements such as nickel, chromium andcobalt which may cause allergic problems should be avoidedin biomaterials, and candidates for alloying include Nb, Zr,

.

J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0 2075

Ta, Mo and Sn (Steinemann, 1996; Kawahara, 1992; Geethaet al., 2001). The low Young’s modulus β-type Ti-based al-loys containing the suitable elements (Nb, Zr, Ta, Mo and Sn)are the most promising materials for biomedical applications(Delvat et al., 2008). Recently new β-type Ti–Nb–Sn based al-loys have been developed (Matsumoto et al., 2007; Matusmotoet al., 2005; Ozaki et al., 2004). Nb is a typical β-stabilizer andSn can increase the strength of Ti-based alloys. Moreover, Snadded into Ti–Nb alloys can stabilize β-phase too (Takahashiet al., 2002). Metastable β-type Ti-based alloys can be obtainedwith reduced content of expensive Nb when an appropriateamount of Sn is added. Some papers report that the Young’smodulus of β-type Ti–Nb–Sn alloys at room temperature candecrease to about 40 GPa with high strength by optimizing al-loy composition (Hanada et al., 2005). This data is very closeto the Young’s modulus of human bones. However, almost allmetallic biomaterials, including Ti-based alloys, are bioinert:these biomaterials cannot effectively interact with the sur-rounding tissues while they are implanted. Ti-based alloyshave poorer bioactivity compared with bioceramic.

Hydroxyapatite (Ca10(PO4)6(OH)2,HA) is one of the mostattractive bioceramic materials for human hard tissueimplants. HA has a similar chemical component and crystalstructure to the natural bone apatite mineral. Many studieshave indicated that HA is biocompatible with hard tissuesof human and has good bioactivity. But poor mechanicalproperties limit HA in load-bearing applications (Edwardset al., 1997; Yamasaki, 1992). Traditionally, HA is coated on theTi-based alloys to improve the biocompatibility of the alloysby many methods (Yu et al., 2003; Choi et al., 2000), but thedifferences in the physical and thermal properties betweenTi-based alloys and HA would cause many serious problems.Recently some studies reported that some excellent Ti–HAbio-composites could be fabricated by the powder metallurgy(PM) technology (Ning and Zhou, 2004; Bishop et al., 1993).

Mechanical alloying (MA) is a solid-state powder met-allurgy process in which all the elemental powdersare alloyed by repeated deformation–cold welding–fracturemechanisms under frequent mechanical impacts. It involvesdiffusion at the atomic level and allows production of variousnon-equilibrium phases such as supersaturated solid solu-tions, nanocrystalline and/or amorphous phases with uniquecharacteristics. MA can synthesize Ti-based alloys with spe-cific microstructures and improved mechanical properties(Zhang, 2004; Fogagnolo et al., 2003; Wen et al., 2006). So syn-thesizing Ti-based alloys and composites by MA becomes afocusable field. The milling time which is the most impor-tant parameter of MA, is responsible for the final structureof powders, microstructure and mechanical properties of sin-tered alloys.

In general, high frequency induction heated sintering(HFIHS) is a rapid sintering method and the sinteringprocess just lasts 1–2 min. HFIHS can inhibit graingrowth and contamination caused by long time and hightemperature in conventional sintering methods (Khaliland Kim, 2007; Kim et al., 2008). In present study,the Ti–35Nb–2.5Sn–15HA bio-composites were fabricated byHFIHS from different ball milling time powders. The sinteredbio-composites were expected to combine the bioactivity ofHA with the mechanical properties of Ti–Nb–Sn alloys. The

Table 1 – Characteristics of Ti, Nb, Sn and HA powderused in MA.

Powder Purity (%) Powder size

Ti 99.5 100 meshNb 99.8 325 meshSn 99.8 325 meshHA – 10 µm

effects of milling time on the microstructure, mechanicalproperties and biocompatibility of sintered bio-compositeswere investigated.

2. Experimental methods

The characteristics of the pure initial Ti, Nb, Sn and HApowders for the synthesis are presented in Table 1. In thisstudy, Ti–35Nb–2.5Sn–15HA (wt%) composites were sinteredfrom 24 h mixed powders and different ball milled timepowders (4 h, 8 h and 12 h) respectively. The mixed powderswere blended for 24 h by a low speed milling machine ina plastic jar under alcohol atmosphere. The weight ratio ofZrO2 balls to powders was at 24:1. The ball milling powderswere conducted in a high energy mechanical milling machine(SPEX 8000 mill/mixer) with sealed stainless steel vial andballs under argon atmosphere at room temperature, and theweight ratio of balls to powder was at 4:1. In the millingprocess 3 wt% of Isopropyl alcohol was used as processcontrol agent (PCA) because it could not pollute the powdersat all. PCA can avoid cold welding between powders andisopropyl alcohol can avoid polluting the elemental powders.The powders were milled for different times from 4 h to 12 hrespectively.

The milled powders were compacted in a cylindricalgraphite die (outside diameter: 35 mm, inside diameter:10.5 mm and high: 40 mm) by a uniaxial cold press. Thegreen compacts were then sintered in a high vacuum furnaceat 1100 ◦C by HFIHS and cooled in air. During the sinteringprocess a uniaxial pressure of 60 MPa was applied.

The shrinkage displacement of composites during thesintering was obtained by measuring vertical displacementusing a linear gage. The phase analysis of the sinteredcomposites was investigated by X-ray diffraction (XRD) withCu Kα radiation. The microstructures of sintered compositeswere observed by scanning electron microscope (JSM-6400,SEM) with an electron dispersive spectroscopy (EDS). Therelative density was tested according to Archimedes principle.

The mechanical properties of the composites weremeasured by Vickers hardness and compression tests. TheVickers hardness was tested at a load of 1 kg for 15 s. For thecompression tests, the sintered composites weremachined toϕ2 × 3 mm.

Cell culture was tested on the sintered composites andpure Ti in 24-well culture plates. MC-3T3 osteoblast-likecells were seeded on the top surface of the samples. Thecells were cultured in Dulbecco’s Modified Eagle’s mediumsupplemented with 100 ml/L fetal bovine serum, 0.15%penicillin and streptomycin mixture at 37 ◦C in a 50 ml/L CO2humidified atmosphere. The cells were cultured for 10 days.

2076 J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0

Fig. 1 – DSC curves of 24 h mixed powders, 4 h milled and12 h milled powders.

The MTT assay was a rapid colorimetric method; it wasused for measuring cell viability and proliferation. After thecells cultured for 10 days the MTT solution was added and theplate with cells was incubated for 2 h. The samples were readin microplate reader by measuring absorbance at 490 nm.

3. Results and discussion

Fig. 1 shows the DSC curves of powders from different millingtime. No noticeable peaks were observed in the curves of 24 hmixed powders and 4 hmilled powders. An endothermal peak

appeared at 366.66 ◦C in the 12 h milled powders curve. Thispeak was obviously attributed to the phase transformationfrom the α-Ti phase to the β-Ti phase. This conformed tothe Ti–Nb phase diagram. The results can indicate that β-Ti powders can be obtained after 12 h ball milling. In theTi–Nb binary phase diagram the transformation temperatureof Ti–35Nb alloys from α-Ti phase to β-Ti phase was about420 ◦C, which is much higher than the temperature in thisstudy. That means the milling process could reduce thetransformation temperature from α-Ti phase to β-Ti phase.Moreover, the addition of Sn and HA could reduce thetransformation temperature too.

Fig. 2 shows the relationship between temperature, shrink-age displacement and time during the Ti–35Nb–2.5Sn–15HAcomposites were sintered by HFIHS. With the increase ofmilling time, the shrinkage displacement of composites grad-ually decreased. The finish time and temperature of sinter-ing also reduced. The shrinkage displacement of 12 h milledpowder did not change above 900 ◦C. This means the sinter-ing completely finished at 900 ◦C which was lower than thedecompose temperature of HA (Ning and Zhou, 2002). This isvery important to keep the biocompatibility of HA.

Fig. 3 shows the XRD patterns of Ti–35Nb–2.5Sn–15HAcomposites sintered from the powders milled for variousperiods. The XRD results show that α-Ti phase peaks stillexisted in the composites sintered from 24 h mixed powdersand 4 h ball milled powders but the α-Ti phase peaksof composites sintered from 4 h ball milled powders wasat a lower 2θ-angle. This phenomena indicates the latticeparameters of Ti increase because of the solid solution of

0.30

0.25

0.20

0.15

0.10

0.05

0.00

0 6 12 18 24

560

600

640

1.70

1.65

1.60

1.55

1.50

1.45

42 48 54 60

900

1000

1100

a

b

a b

Fig. 2 – Relationship of temperature and shrinkage with sintering time during HIFHS.

J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0 2077

d

c

b

a

Fig. 3 – X-ray diffraction patterns of composites sinteredfrom different powders: (a) 24 h mixed, (b) 4 h milled, (c) 8 hmilled and (d) 12 h milled.

Ti (Nb, Sn). The XRD patterns of the composites sinteredfrom 8 and 12 h milled powders show that the α-Ti phasepeaks almost disappear. It suggests that all α-Ti phasehas transformed into β-Ti phase. Because Nb is a β phasestabilizing element, it can form a homogeneous solid solutionin β-Ti phase even from a supersaturated solution (Elias et al.,2006). Also Sn can be soluble in Ti to form solid solution. Somepapers reported that the existence of Ti would reduce thedecomposition temperature of HA to 1000 ◦C below (Ning andZhou, 2004).

In this study, the sintering temperature of all compositeswas controlled at 1100 ◦C. And a peak correspondingto Ca3(PO4)2 (TCP) is still observed in all the sinteredcomposites. This phenomenon means that some HA wasdecomposed during the sintering. There are some new phasesformed in the sintered composites due to the reactionduring sintering, such as CaTiO3, Ti2O, TiO2 and TixPywhich are important to form bone-like apatite according tosome reports. The reaction in the sintering process could beexpressed as the following illustrative equation:

Ti + Ca10(PO4)6(OH) → Ti2O + CaTiO3 + TiO2 + TCP + TixPy.

Fig. 4 shows the scanning electronmicrograph (SEM) of theTi–35Nb–2.5Sn–15 HA composites sintered from 24 h mixedpowders and 4 h, 8 h, 12 h milled powders respectively.There are distinct gray regions and white regions in thecomposite sintered from 24 h mixed powders. Elements Tiand Nb are distributed in distinct regions in the compositesintered from 24 h mixed powders (Fig. 4(a)). According to theX-ray mapping analysis results (Fig. 5(a)), the gray regions areTi rich areas and the white regions are Nb rich areas. Thisindicates that mechanical alloying did not happen during the24 h mixing. The microstructure of the sintered compositefrom 4 h milled powders is shown in Fig. 4(b). There are stilldifferent component regions, but the region size is obviouslysmaller than that in Fig. 4(a). It means the MA process beganto work. Fig. 4(c) and (d) are microstructure of the compositessintered from 8 h and 12 h milled powders respectively.Compared with the composites sintered from 24 h mixed and4 h milled powders, ultra fine particles (PFG) could be foundin the composites sintered from 8 h milled and 12 h milledpowders. There are still some bigger particles in Fig. 4(c) and

Table 2 – Microhardness and relative density ofcomposites sintered from different milling timepowders.

Sinteredcomposites

Microhardness(HV)

Relative density(%)

0 h milled 528.19 94.224 h milled 948.30 95.558 h milled 1069.74 96.2312 h milled 1417.39 97.32

their shapes are not very regular. The microstructure of thecomposites sintered from 12 h milled powders shows theβ-phase grains exist as small particles. the average particlesize is about 100 nm and element distribution in the sinteredcomposites is very homogeneous (as shown in Fig. 5(c)).

Table 2 shows the Vickers microhardness and relativedensity of composites sintered from different powders. AsTable 2 shows, both Vickers microhardness and relativedensity increase with the milling time. The Vickersmicrohardness of the composites sintered from 12 h milledpowders is 1416 HV, which is much higher than the others.The hardness of sintered composites is influenced by manyfactors, among these factors the most important one ismilling time of powders. The grain refinement and thesupersaturated solid solution of Nb into Ti would improvewith the increase of milling time, then the microhardnessincreases. Mangal Roy found the presence of Ca3(PO4)2 inTi would increase the hardness too (Mangal et al., 2008).The milling time also can effect on the density of sinteredcomposites so the relative density of samples sintered from12 h milled powder increase to 97.32%.

The compression tests have been carried out on thecomposite samples sintered from 4 h milled and 12 hmilled powders respectively. Fig. 6 shows the compressionstrain–stress curves. The figure shows that two kind sinteredcomposite samples both have high compression strength.Mechanical properties values are summarized in Table 3.There is no yield band in the strain–stress curves and justthe elastic break-down behavior takes place in two compositesamples. The yield strength (σ0.2) of composite samplessintered from 12 h milled powder can be 870 MPa, which ismuch higher than nature bones’ (89–295 MPa) (Geetha et al.,2009). The compressibility of the composites is 5.7%. Thesupersaturation solid solution of Nb leads to an increase ofyield strength and elongation. The Young’s modulus of thetwo sintered composite samples sintered from 4 h milledand 12 h milled powders are 20 GPa and 22 GPa respectively,which approximate human bones. The Young’s modulus ofthese two composite samples is much lower compared withthose of pure Ti and Ti–6Al–4V alloys as references. It isreported that β-type Ti has a lower Young’smodulus; however,the foregoing XRD analyses indicate the composite samplessintered from 4 h milled powders is α + β phase Ti. So theYoung’s modulus of composite samples after sintering wouldbe affected by some other factors, such as relative density(Wang et al., 2009).

The MTT assay was used for measuring the cell viabilityand the proliferation of osteoblast-like cells (MC-3T3) on thesintered composites and pure Ti as reference. The optical

2078 J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0

a b

c d

50µm 50µm

5µm 5µm

Fig. 4 – SEM observations of composites sintered from different powders: (a) 24 h mixed, (b) 4 h milled, (c) 8 h milled and (d)12 h milled.

a b

c

Nb Nb

Ca

Ca

CaTi

Ti

Ti

Nb

Fig. 5 – X-ray mapping scanning analysis of composites sintered from different milled time powders: (a) 24 h mixed, (b) 4 hmilled, (c) 12 h milled.

Table 3 – Summary of mechanical properties of Ti35Nb2.5Sn15HA composites sintered from different powders.

Ti35Nb2.5Sn15HA Elastic modulus (MPa) Compressive strength (MPa) Yield strength (σ0.2, MPa) Elongation (%)

4 h milled 20 481.61 455.3 4.712 h milled 22 877.49 870.36 5.7Pure Ti 100 – – –Ti–6Al–4V 100–120 – – –

J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0 2079

12h milled

4h milled

Fig. 6 – Compression strain–stress curves of compositessintered from 4 h milled and 12 h milled powders.

Fig. 7 – Results of cell culture of Ti–Nb–Sn–15HAcomposites and pure Ti.

density (OD) value of MTT culture solution could indicate thecell viability and proliferation on the samples. Fig. 7 showsthe results of OD value of culture solution of different samplesafter cell culture for 10 days. It can be seen that the OD valueof all the sintered composites is higher than pure Ti. Thecomposites sintered from 12 h milled powders show highestOD value. This mainly results from good surface conditionand high contents of HA in Ti. The MTT results indicate thatthe composites sintered from 12 h milled powders are morebiocompatible.

4. Conclusions

In this study, the Ti–35Nb–2.5Sn–15HA bio-composites weresynthesized by HEMM and HFIHS. The microstructure,microhardness, relative density and compression propertieswere investigated. The conclusions are as follows:

The β-phase Ti-based powders were obtained after 12 hball milling, and the transform temperature decreased due tothe addition of Sn and Nb.

The homogeneous β-phase ultra fine grain Ti–35Nb–2.5Sn–15HA composites were synthesized by HFIHS in 60 sat 1100 ◦C. Some new phases appear in the sintered

Ti–35Nb–2.5Sn–15HA composites from 12 h milled powdersdue to the reaction of Ti and HA, such as Ti2O, TiO2,Ca3 (PO4)2, CaTiO3 and TixPy. Some of these phases are goodfor forming bone-like apatites.

The composites sintered from 4 h milled and 12 h milledpowders have a very low elastic modulus and the data are20 GPa and 22 GPa respectively which approximate naturalbones. The compression strength of composites sintered from12 hmilled powders is 877MPa. And the compressibility of thecomposite samples is 5.7%.

The osteoblast-like cells on the sintered compositesshow very good cell viability and the proliferation. Thecomposites sintered from 12 h milled powders have goodbiocompatibility.

Acknowledgments

The authors acknowledge the support from the NaturalScience Foundation of Heilongjiang Province Project (ZJY0605-02) China and the National Research Foundation of Korea(NRF) grant funded by the Korea Government (No. 310703002).

R E F E R E N C E S

Bishop, A., Lin, C.Y., Navaratnam, M., Rawlings, R.D., Mcshane,H.B., 1993. A functionally gradient material produced by apowder metallurgical process. J. Mater. Sci. Lett. 12, 1516–1518.

Choi, J.M., Kim, H.E., Lee, I.S., 2000. Ion-beam-assisted deposition(IBAD) of hydroxyapatite coating layer on Ti-based metalsubstrate. Biomaterials 21, 469–473.

Delvat, E., Gordin, D.M., Gloriant, T., Duval, J.L., Nagel, M.D., 2008.Microstructure, mechanical properties and cytocompatibilityof stable beta Ti–Mo–Ta sintered alloys. J. Mech. Behav. Biomed.Mater. 1, 345–351.

Edwards, J.T., Brunski, J.B., Higuchi, H.W., 1997. Mechanical andmorphologic investigation of the tensile strength of a bonehydroxyapatite interface. J. Biomed. Mater. Res. 36, 454–468.

Elias, L.M., Schneider, S.G., Schneider, S., Silva, H.M., Malvisi,F., 2006. Microstructural and mechanical characterizationof biomedical Ti–Nb–Zr(–Ta) alloys. Mater. Sci. Eng. A 432,108–112.

Fogagnolo, J.B., Velasco, F., Robert, M.H., Torralba, J.M., 2003. Effectof mechanical alloying on the morphology, microstructure andproperties of aluminium matrix composite powders. Mater.Sci. Eng. A 342, 131–143.

Geetha, M., Singh, A.K., Asokamani, R., Gogia, A.K., 2009. Ti basedbiomaterials, the ultimate choice for orthopaedic implants—areview. Prog. Mater. Sci. 54, 397–425.

Geetha, M., Singh, A.K., Muraleedharan, K., Gogia, A.K., Asoka-mani, R., 2001. Effect of thermomechanical processing on mi-crostructure of a Ti–13Nb–13Zr alloy. J. Alloys Compd. 329,264–271.

Hanada, S., Matsumoto, H., Watanabe, S., 2005. Mechanicalcompatibility of titanium implants in hard tissues. Int. Congr.Ser. 1284, 239–247.

Kawahara, H., 1992. Cytotoxicity of implantable metals and alloys.Bull. Japan Inst. Met. 31, 1033–1039.

Khalil, Abdel-razek K., Kim, S.W., 2007. High-frequency inductionheating sintering of hydroxyapatite-(Zro2+3%Mol Y2o3) bioce-ramics. Mater. Sci. Forum 534, 1033–1036.

Kim, H.C., Kim, D.K., Woo, K.D., Ko, I.Y., Shon, I.J., 2008.Consolidation of binderless WC-TiC by high frequencyinduction heating sintering. Int. J. Refract. Met. H 26, 48–54.

2080 J O U R N A L O F T H E M E C H A N I C A L B E H AV I O R O F B I O M E D I C A L M A T E R I A L S 4 ( 2 0 1 1 ) 2 0 7 4 – 2 0 8 0

Long, M., Rack, H.J., 1998. Titanium alloys in total hipreplacement-a materials science perspective. Biomater 19,1621–1639.

Mangal, R., Vamsi Krishna, B., Bandyopadhyay, A., Bose, S., 2008.Laser processing of bioactive tricalcium phosphate coatingon titanium for load-bearing implants. Acta. Biomater. 4,324–333.

Matsumoto, H., Watanabe, S., Hanada, S., 2007. Microstructuresand mechanical properties of metastable β TiNbSn alloys coldrolled and heat treated. J. Alloys Compd. 439, 146–155.

Matusmoto, H., Watanabe, S., Hanada, S., 2005. Beta TiNbSn alloyswith low Young’s modulus and high strength. Mater. Trans. 46,1070–1078.

Niinomi, M., 2008. Mechanical biocompatibilities of titaniumalloys for biomedical applications. J. Mech. Behav. Biomed.Mater. I, 30–42.

Ning, C.Q., Zhou, Y., 2004. On the microstructure of biocompositessintered from Ti, HA and bioactive glass. Biomaterials 25,3379–3387.

Ning, C.Q., Zhou, Y., 2002. In vitro bioactivity of a biocompositefabricated from HA and Ti powders by powder metallurgymethod. Biomaterials 23, 2909–2915.

Ozaki, T., Matsumoto, H., Watanabe, S., 2004. Beta Ti alloys withlow Young’s modulus. Mater. Trans. 45, 2776–2779.

Steinemann, S.G., 1996. Metal implants and surface reactions.Injury 27, SC16–SC22.

Taddei, E.B., Henriques, V.A.R., Silva, C.R.M., Cairo, C.A.A., 2004.Production of new titanium alloy for orthopedic implants.Mater. Sci. Eng. C24, 683–687.

Takahashi, E., Sakurai, T., Watanabe, S., Masahashi, N., Hanada,S., 2002. Effect of heat treatment and Sn content onsuperelasticity in biocompatible TiNbSn alloys. Mater. Trans.43, 2978–2983.

Wang, X.J., Li, Y.C., Xiong, J.Y., Hodgson, P.D., Wen, C.E., 2009.Porous TiNbZr alloy scaffolds for biomedical applications.Acta. Biomater. 5, 3616–3624.

Wen, C.E., Yamada, Y., Hodgson, P.D., 2006. Fabrication of novelTiZr alloy foams for bio-medical applications. Mater. Sci. Eng.C 26, 1439–1444.

Yamasaki, H., 1992. Osteogenic response to porous hydroxyapatiteceramic under the skin of dogs. Biomaterials 13, 308–314.

Yu, L.G., Khor, K.A., Li, H., Cheang, P., 2003. Effect of sparkplasma sintering on the microstructure and in vitro behaviorof plasma sprayed HA coatings. Biomaterials 24, 2695–2705.

Zhang, D.L., 2004. Processing of advanced materials using high-energy mechanical milling. Prog. Mater. Sci. 49, 537–560.

Zhou, Y.L., Niinomi, M., Akahori, T., 2004. Effects of Ta content onYoung’s modulus and tensile properties of binary Ti–Ta alloysfor biomedical applications. Mater. Sci. Eng. A 371, 283–290.

Zhu, S.L., Wang, X.M., Xie, G.Q., Qin, F.X., Yoshimura, M., 2008. A.Inoue. Formation of Ti-based bulk glassy alloy/hydroxyapatitecomposite. Scripta Mater. 58, 287–290.