Acta Biomaterialia 8 (2012) 16611669

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Acta Biomaterialia
journal homepage: www.elsevier.com/locate/actabiomat

Review

A new look at biomedical Ti-based shape memory alloys

Arne Biesiekierski a, James Wang a, Mohamed Abdel-Hady Gepreel b, Cuie Wen a,
a b

Faculty of Engineering and Industrial Science, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia Department of Materials Science and Engineering, EgyptJapan University of Science and Technology, Borg El Arab City, Alexandria 21934, Egypt

a r t i c l e

i n f o

a b s t r a c t
Shape memory alloys (SMAs) are materials that exhibit a distinct thermomechanical coupling, one that gives rise to a wide variety of applications across a broad range of elds. One of the most successful roles is in the construction of novel medical implants. Unfortunately, concerns have been raised about the biocompatibility of the most popular SMA, nitinol (NiTi), due to the known toxic, allergenic and carcinogenic properties of nickel. Given the unique capabilities of SMAs, it is apparent that there is a need for a new class of alloys alloys that exhibit the full range of shape memory abilities yet are also free of any undesirable side effects. This article reviews the literature surrounding SMAs and identies the metals Ti, Au, Sn, Ta, Nb, Ru and Zr as candidates for the production of thoroughly biocompatible SMAs. Hf and Re are also promising, though more research is necessary before a denitive statement can be made. Further, the Ti(Ta,Nb)(Zr,Hf) alloy system is particularly suited for orthopaedic implants due to a reduced Youngs modulus. However, concerns over this systems shape memory properties exist, and should be taken into consideration. Alternate alloy systems that demonstrate higher bulk moduli may still be considered, however, if they are formed into a porous structure. Due to the nature of the alloying components, blended elemental powder metallurgy is recommended for the manufacture of these alloys, particularly due to the ease with which it may be adapted to the formation of porous alloys. Crown Copyright 2012 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. All rights reserved.

Article history: Received 26 October 2011 Received in revised form 10 January 2012 Accepted 16 January 2012 Available online 28 January 2012 Keywords: Mechanical properties Titanium Shape memory Biocompatibility Superelasticity

1. Introduction Since the discovery of their unique properties, SMAs have been the focus of signicant interest for a wide variety of applications. With the discovery of nitinol (NiTi), a mechanically impressive titanium alloy that exhibits a large shape memory effect (SME), these applications have sky-rocketed. Ranging from the prosaic, for use in mobile phone antennae and eyeglass frames, to cutting-edge roles in actuation and noise control, the mechanical abilities rising from the SME are undeniably useful. Of particular interest is the role SMAs may play in biomedical implants, as a number of useful items have already been produced, including orthodontic implants, stents (as shown in Fig. 1), orthopaedic staples and even occluding structures to heal congenital heart defects [1,2]. While alternatives to many of these items existed in some form prior to the use of SMAs, the thermo-elastic transition of the SME has allowed for signicant improvements. Unfortunately, concerns have been raised about the composition of nitinol, specically with the presence of nickel, a known allergenic carcinogen that exhibits one of the highest sensitivities

Corresponding author. Tel.: +61 3 92145651; fax: +61 3 92145050.

E-mail address: cwen@swin.edu.au (C. Wen).

in metallic allergen tests [3]. While techniques such as surface modication have been researched in an attempt to mitigate this, there is nevertheless an incentive to produce a completely biocompatible implant material still capable of exhibiting the desired SME. A number of authors have attempted the production of natively biocompatible SMAs; for example, extensive work on TiNb and the related TiNbX system (where X = Zr, Ta, Au, O) has yielded alloys with superelastic strains as high as 4.2%, sufcient for most applications [46] without sacricing biocompatibility. However, while these are extremely promising, there is another concern beyond the biochemical effects of the alloy: the Youngs modulus of equiatomic NiTi is signicantly higher than human bone [7,8]. Though a high Youngs modulus is acceptable for a number of implantation roles, the high stiffness can lead to problems when utilized in orthopaedic implants [9]. Herein lies a problem; although higher than that of bone, the elastic modulus of NiTi is still lower than that of many other alloys. As obtaining still lower moduli requires a dedicated effort during the design process, it is clear that the reduction of modulus most be considered concurrently with the thermoelastic behavior of the alloy. To that end, this article will review the literature concerning the eld of biomedical SMAs and seek to outline and address the primary concerns associated with designing an SMA without sacricing bio- or osteocompatibility.

1742-7061/$ - see front matter Crown Copyright 2012 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. All rights reserved. doi:10.1016/j.actbio.2012.01.018

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2. Design considerations for novel SMAs for biomedical applications In order to identify promising new alloy systems, it is benecial to dene precisely where existing alloys are lacking, and what features would yield the most satisfactory alloy for biomedical roles. First and foremost of these features is the biological compatibility of the alloy, followed by its mechanical properties. Also of note is the extent of the SME each alloy exhibits; both the degree of recoverable strain and the temperatures at which the alloy undergoes its characteristic transformation can have a huge effect on the applicability of the alloy to a biomedical role. 2.1. Biological considerations Interactions in the biological environment are extremely complex, and so terms such as biocompatibility are difcult to pin down. A materials biocompatibility may change depending purely on where in the body it is utilized, and the role it is expected to perform. In this review, the primary concerns are whether the element is known for adverse effects to the biological process; whether the metal is carcinogenic (cancer causing), mutagenic (mutation causing), genotoxic (DNA damaging) or cytotoxic (cell destructing/killing); whether it incites an allergic response; and whether it can resist the corrosive biological environment. While an individual metals answers cannot conclusively determine the nal alloys biocompatibility, answering these questions can at least allow reasonable predictions to be made. Bearing this in mind, it is rst necessary to address the failings of the current alloying element, nickel. 2.1.1. Biological impact of nickel As mentioned previously, nickel (Ni) is known to be extremely poor in terms of biocompatibility, showing negative impacts virtually across the board in a range of bioassays. Issues include susceptibility to corrosion via biological uids, a high relative cytotoxicity [10,11] and haemolytic behaviour in particulate form [12]. In addition to this, concerns over its genotoxicity [13], carcinogenicity [14,15] and potential mutagenicity [16,17] abound. Nis cytotoxicity and susceptibility to corrosion are undesirable, but are at least somewhat mitigated by the formation of a stable TiO2 layer. Far more concerning, however, are the reports of mutagenicity, genotoxicity and carcinogenicity. Whereas cytotoxicity is a concentration-dependent phenomenon, carcinogenicity is stochastic, and even a single cancerous cell can ultimately lead to a fatal tumour. Given this, it is apparent that any new alloy must not contain elements that exhibit carcinogenicity, and ideally should also be nongenotoxic and non-mutagenic, as these can lead to carcinogenicity. A high resistance to corrosion and a low level of cytotoxicity are also desirable. 2.1.2. Biological impact of the 3d transition metals The 3d transition metals are titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu) and the aforementioned Ni. The majority of these metals are used in existing biomedical alloys approved for human implantation, and thus this group serves as an appropriate starting point for analysis. As a result of their roles, the majority are well understood in terms of biocompatibility. Unfortunately, however, with the exception of Ti, all of them exhibit some degree of negative biological impact. Cu, Fe and Mn, while not classied as carcinogenic (with the exception of certain iron carbohydrate complexes [18]), are demonstrably cytotoxic and highly prone to corrosion [10]. In addition to this, a review by Lima et al. [19] has identied evidence for the genotoxicity of both Fe and Mn. There is also evidence to suggest that

prolonged low-level exposure to Cu can act to suppress cell viability [20]. Another 3d transition metal, Cr, has excellent corrosion resistance and extremely low cytotoxicity, but there are concerns over its genotoxicity; while traditionally only Cr6+ (which is not formed via corrosion) was considered carcinogenic [14,21], research has indicated Cr3+ may be genotoxic as a free ion [22], and carcinogenic in certain complexes [23]. Despite their roles in implant materials, Co and V are considered carcinogenic and highly cytotoxic, with varying evidence of genotoxicity and mutagenicity in the existing literature [14,16,24,25]. Furthermore, Co and CoCr metal particulates (such as might be produced from abrasion of metal implants) demonstrate high levels of haemolysis [12]. Finally, Ti is extremely well studied, and has been shown to demonstrate excellent biocompatibility and corrosion resistance, with a moderate to low cytotoxicity [10,24,26]. With the exception of the titanocene organic complex, it is also considered non-carcinogenic [18]. 2.1.3. Biological impact of the 4d transition metals The 4d transition metals are zirconium (Zr), niobium (Nb), molybdenum (Mo), technetium (Tc), ruthenium (Ru), rhodium (Rh), palladium (Pd) and silver (Ag). Relative to the 3d metals, these have not been quite so widely used in implant materials, though several have been used in dental alloys. Pd, a noble metal that has found use in dental alloys, is unfortunately also known to be both a carcinogen and an allergen [11]. Likewise, a second dental metal, Ag, has also proven to be a poor candidate for implantation. While it has a long history of use in antibacterial roles [27], the metal ion is highly cytotoxic in vitro [10,24], though this may be moderated somewhat by metallothione in complexes in vivo [27]. In implantation into living muscle tissue, Ag demonstrated signicantly worse biocompatibility than either 316L stainless steel or Ti [28], and evidence exists for the metal being an allergen [11,27]. Furthermore, the very antibacterial role of the metal has been known to cause clusters of calcareous bacterial/fungal infections that resist both immunological and antibiotic attack [27]. A component of 316L steel, Mo is not considered cytotoxic [25,29]. However, it has been shown to have extremely deleterious effects on the rate of cell proliferation, mitochondrial activity and the volume of the cells cultured on it [30]. Furthermore, it has also been linked to occurrences of in-stent restenosis due to allergenic effects [3]. Tc can be disregarded completely, as it has no known stable isotopes [31]. Rh, another noble metal, exhibits some degree of carcinogenicity in mice, and is also considered to be mutagenic and genotoxic [11,32,33]. Ru has not been as widely studied, but has found some application in dental alloys. Ru3+, the most common oxide, demonstrates low cytotoxicity [10] and is not known to be mutagenic, carcinogenic or allergenic [11,16], though a tetroxide form is notable for being highly toxic and potentially explosive [34]. This is unlikely to be an issue, however, as Ru is known to enhance the corrosion resistance of titanium by several orders of magnitude with even a 0.1% addition [34]. The last two 4d transition metals, Zr and Nb, are extremely promising, as both are extremely biocompatible, exhibiting low ionic cytotoxicity in vitro, excellent biocompatibility in vivo, no evidence of mutagenicity or carcinogenicity, a good resistance to corrosion, and osteocompatibility equalling or exceeding that of Ti [10,11,26,29,30,35]. 2.1.4. Biological impact of the 5d transition metals The 5d transition elements are hafnium (Hf), tantalum (Ta), tungsten (W), rhenium (Re), osmium (Os), iridium (Ir), platinum (Pt) and gold (Au). This group of metals is also promising; though, once again, the majority are unsuitable, several elements nevertheless demonstrate excellent biocompatibility. Due to the formation of highly toxic, highly volatile oxides and a poor corrosion resistance, Os can be considered unsuitable for implants [34]. W has

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Fig. 1. From the top: two expanded NiTi stents, a stent introducer containing compressed stent and a stent removal set. Reproduced from Song et al. [2].

exceeds that of hexavalent chromium in mammalian ovary cells [48], and a relatively high cytotoxicity [10]. It should be noted, however, that the stannous (Sn2+) state is rapidly oxidized to the stannic (Sn4+) state, which is also the ion produced by oxygen attack. This alternate ion species, by comparison, demonstrates a good corrosion resistance along with exceptionally low cytotoxicity and no evidence of genotoxicity or mutagenicity [10,16,48]. As such, Al and Zn can be regarded as unsuitable for implantation, while Sn can be considered suitable. Having briey reviewed the common alloying elements, a summary of which is presented in Table 1, it can be seen that Ti, Au, Sn, Ta, Nb, Ru and Zr can be classed as highly biocompatible. Hf and Re hold promise for further research, but must be treated with caution at present. All other elements reviewed are considered less satisfactory. 2.2. Mechanical considerations

also been proven to be unsuitable; while only moderately cytotoxic [10], the metal is extremely prone to corrosion [36], and recent evidence has demonstrated genotoxicity due to tungsten microparticles [37]. Furthermore, concerns have been raised about a possible carcinogenic link, with high levels of W in solution possibly leading to an increase in leukaemia in children [38]. Pt is mutagenic in the form of metal salts, and some organic platinum compounds may exhibit carcinogenicity, though these effects are greatly mitigated by its excellent corrosion resistance [11,18]. Ir has been used in oxide form in the production of neural electrodes due to its excellent electrochemical properties and satisfactory biocompatibility [39,40]. However, the majority of biocompatibility studies have focused on the interaction of Ir with neuronal cells, which have only limited relevance to the current study. Further, other studies have identied both mutagenicity and a relatively high cytotoxicity [10,16]. The biocompatibility of Hf and Re have been poorly studied[34], though work by Matsuno et al. [26] suggests excellent bioand osteocompatibility, with no evidence of ion release after 4 weeks in vivo. Au is another commonly used biomedical metal. While it exhibits a relatively high cytotoxicity as Au3+ [10,11], the metals excellent corrosion resistance greatly mitigates this. Studies on the carcinogenicity are somewhat mixed; while thin foils and disks of implanted Au have been reported to produce local sarcomas, there is doubt as to whether sarcomas can be considered an adequate means of assessment [41,42]. Sarcoma response is near universal regardless of the implanted material, whereas a separate study involving colloidal gold nanoparticles produced no cancer [43]. Given the huge increase in reactivity associated with nanoparticles, this is strongly dismissive of a chemical cause for the cancers. Ta demonstrates excellent corrosion resistance, low cytotoxicity, and good osteocompatibility [10,26,30], though it also exhibits sarcomas due to the implantation of thin foils [44,45]. Given the nature of the studies, this article chooses to disregard the claim of sarcoma-related carcinogenicity in Ta and Au foils at this time. 2.1.5. Biological impact of selected other metals While a further row of transition metals exist, these can be disregarded due to the lack of stable isotopes. That said, metals outside the transition elements are commonly utilized in alloys, specically zinc (Zn), aluminium (Al) and tin (Sn). Zn, an important dietary element, also exhibits an extremely high cytotoxicity [11,24], and elevated levels of Zn have been shown to cause corresponding decreases in Fe and Cu uptake [46]. Al is already utilized in an existing biomedical alloy, Ti6Al4V, but links to neurodegenerative disease, genotoxicity and possible necrosis have been reported in the literature [19,30,47]. Finally, Sn, in the form of SnCl2, has demonstrated a pronounced genotoxic effect that

In addition to the biocompatibility of any potential alloying element, it is also necessary to consider the mechanical environment in which the alloy will be utilized. For biological systems, this means implants will need to perform for long periods in a warm, corrosive environment, in close contact with comparatively soft organic tissue. As a result, considerations about the mechanical nature of the implant must be made; foremost of these is that of the effects of the implant contacting the surrounding tissue. 2.2.1. Implants and stress shielding In soft tissue, such as with a stent, this is less of a concern; the tissue is not load-bearing, and can adapt to accommodate the implant. Indeed, in stenting applications, a high Youngs modulus is necessary to provide suitable resistance to collapse [49]. However, problems can arise if the implant is inserted into a load-bearing bone, as might be the case with a hip implant or orthopaedic staple. If the implant exhibits a substantially higher elastic modulus than the surrounding bone, a phenomenon known as stress shielding can occur [9,50] whereby applied stresses are taken up by the implant rather than by the bone. This leads to resorption of the bone by the body, which may in turn lead to complications such as bone fracture and loosening of the implant [50]. The Youngs modulus of cortical (dense) bone has been found to range from 6.0 to 26.6 GPa [8,51] and, while reports for NiTi are varied, the literature lists values of 4855 GPa as the lower bound for Youngs moduli of bulk NiTi [7,52,53], which exceeds that of bone. Despite this, NiTi still exhibits a far lower Youngs modulus than the other common biomedical alloys (commercially pure (CP) Ti, CoCr, 316L stainless steel and Ti6Al4V) [52], further underlining the need for low-modulus alloys. 2.2.2. The relationship between alloy composition and crystal phase In most titanium alloys, the alloy exists in one of two major phases, or a combination thereof: a high temperature austenitic phase and lower temperature martensitic phase. While a number of different phases and transitions are possible, the higher temperature state is often a b-phase, a body-centred cubic (bcc) structure, while the lower temperature phase exhibits a hexagonal closepacked (a) martensitic phase. This distinction is important; while pure a-phase (e.g. CP Ti) and mixed a + b-phase (e.g. Ti6Al4V) alloys have excellent strength and creep resistance, b alloys have the advantages of better fatigue resistance and a lower Youngs modulus [30,54,55]. b-phase alloys are thus preferable; the advantages of the a-phase yield little benet at the comparatively low temperatures and stresses associated with implantation roles. By contrast, the lower Youngs modulus of the b-phase is particularly benecial for orthopaedic implants, and a high fatigue resistance is desirable for any long term implant.

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Table 1 Biological impact: Red indicates a serious concern; Yellow indicates a moderate concern; Green indicates minimal/no concern [1048].

Other: Refers to issues beyond those already listed. For example; haemolysis, neurological effects, etc. For more detail, refer to the relevant element in text.

Table 2 Selected Ti alloying elements grouped by stabilizing effect [55,59]. Element V Nb Mo Ta Re Cr Mn Fe Co Ni Cu Type b-Isomorphous b-Isomorphous b-Isomorphous b-Isomorphous b-Isomorphous b-Eutectoid b-Eutectoid b-Eutectoid b-Eutectoid b-Eutectoid b-Eutectoid Element Pd Ag W Pt Au Hf Zr Sn Al O N Type b-Eutectoid b-Eutectoid b-Eutectoid b-Eutectoid b-Eutectoid Neutral/b-Iso Neutral/b-Iso Neutral/b-Eut

a a a

Given this, it is necessary to select an alloy composition that will exist in the b-phase at the ambient temperatures. Early attempts to develop novel b alloys (and thus SMAs) used a somewhat trial-and-error approach; alloying elements were classied by their general effect as either b-stabilizing elements that lowered the transition temperature, a-stabilizers that raised the temperature or neutral elements that had no signicant effect on the transition temperature. While this was ne for binary alloys, more complicated systems did not always behave exactly as expected. A short list of alloying elements grouped by their stabilizing effect is presented in Table 2. The work by Morinaga et al. [56,57] has greatly simplied the process. By identifying the relationship between phase, bond order (the covalent bond strength between Ti and the alloying element, Bo) and the metal d-orbital energy level (Md), a map of the phase composition can be produced (see Fig. 2). As a result, the formulation of a novel alloy with a desired phase is as simple as choosing a point within the region associated with desired phase and noting the Bo and Md values associated with it. As the alloy bond order

Fig. 2. Alloying vectors for a selection of elements with bcc Ti. The units of Md are eV.

and d-orbital energy levels (Bo , M d ) are merely the compositional averages of those of the component elements, e.g.

Bo

X i Bo i X Md X i M d i

1 2

where Xi represents the atomic fraction of a given element, it is a relatively simple affair to calculate the necessary ratios. Bo and Md values for a selection of elements are provided in Table 3, and the alloying vectors associated with the binary alloys of each element are presented in Fig. 2. An extended phase map, showing the phase behaviour for higher BoMd values, is given in Fig. 3.

A. Biesiekierski et al. / Acta Biomaterialia 8 (2012) 16611669 Table 3 List of Bo and Md values for selected elements alloying with bcc Ti [57]. Element Ti Ni Zr Nb Ru Hf Ta Re Ir Au Sn Bo 2.790 2.412 3.086 3.099 2.704 3.110 3.144 3.061 3.168 1.953 2.283 Md (eV) 2.447 0.724 2.934 2.424 0.859 2.975 2.531 1.490 0.677 0.258 2.100

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general categories: b-isomorphous and b-eutectoid [55,59]. A b-isomorphous stabilizer (such as Zr, Hf, Nb, Ta or Re) is one in which each of the alloying species is completely soluble in the other and they share the same crystal phase. As a result, the metal typically exhibits an extremely simple phase diagram, and on cooling to ambient temperature will yield purely b- and/or a-phase. This contrasts to a b-eutectoid stabilizer (e.g. Ni, Fe, Au, Cr or Pt), where the alloying species is not perfectly soluble in the bulk Ti. This results in a eutectoid phase system, with the cooling alloy liable to form a mixture of additional phases that depends on the specic atomic species present. This, in turn, leads to difculty in manufacturing the desired SMA as the formation of additional phases can act to leach alloying elements away from the chosen ratio, changing the shape memory and material properties. The eutectoid effects can be mitigated somewhat via sufcient addition of isomorphous stabilizers [59], so it is still possible to at least partially utilize b-eutectoid stabilizers. However, to avoid incurring a pronounced eutectoid response, the use of b-eutectoid stabilizers should be minimized, and binary alloys with eutectoid stabilizers avoided. 2.2.5. The relationship between porosity and youngs modulus Along with controlling the composition, a second approach to reducing the observed stiffness exists, one that allows the use of a far wider range of alloy compositions: casting or otherwise forming the metal into a porous, sponge-like structure has been shown to effectively reduce the observed Youngs modulus according to the literature [50,53,6064]. The relationship has been formalized in work by Gibson and Ashby [65], who established a theoretical model that links an elastic modulus with the density of the material. This can be expressed as

Ep =Es Cqp =qs 2

Fig. 3. Extended phase diagram for bcc Ti. The values in parenthesis are the approximate Youngs moduli in GPa; values of Md are in eV.

2.2.3. The relationship between phase stability and elastic properties However, while b-phase alloys exhibit lower Youngs moduli in general, care must still be taken in selecting precisely the right composition; the b-phase alloys studied work by Abdel-Hady et al. [57] exhibit a wide range of moduli in alloys differing compositionally by only a few percent. This paper is of note, however, because of the relationship observed between an alloys location on the Bo M d plot and its Youngs modulus. Specically, the moduli of alloys existing near the transus line were seen to decrease as both Bo and M d increased. The modulus was also dependent on the proximity to the transus line; alloys closest to the transus exhibited the lowest moduli. Extrapolating this observation beyond the range investigated suggests that a fertile region for investigation lies in the neighbourhood of Bo 2:96 eV; M d 2:65 eV, which is easily reachable, given the alloying vectors of Ta, Nb, Zr and Hf. This also supports the theoretical modelling of Song et al. [58], which identify Ta, Nb and Zr as acting to lower the elastic modulus of b titanium, while concurrently increasing the strength. 2.2.4. Eutectoid vs. isomorphous stabilizers Another brief consideration for the choice of b-stabilizing elements is the category of stabilizer used. b-stabilizers fall into two

where Ep is the modulus of the porous sample, Es the modulus of the solid sample, C a constant depending on pore structure, and qp and qs are respectively the densities of the porous and solid samples. This method has numerous advantages; rst and foremost, it allows for the design of a far wider range of alloys, able to avoid stress shielding, than a purely compositional approach. Additionally, the implant displays an interconnected porous architecture that allows new bone tissue in growth and transport of body uid, and therefore leads to greatly improved osteoinduction [50]. While there are inarguable benets, there are also downsides to this method. Research by Wolfarth and Ducheyne [66] has shown that mixed porous/solid materials demonstrate a maximum fatigue strength one-third that of a fully solid sample, while a comparison between porous and bulk Ti alloys indicates a similar or worse reduction for fully porous samples [50,67,68]. Porous samples also generally exhibit greatly increased corrosion rates. This is attributed to both the increase in surface area and (particularly in samples with small, sparsely interconnected pores) the inhibiting effect on the formation of passivation layers [50,69]. These corrosion effects can be further increased due to applied stresses, such as would be experienced in orthopaedic implantation roles [50]. Therefore, while porous implants hold signicant promise, care must be taken in their implementation. 2.3. Shape memory considerations Up to this point, this article has predominantly addressed concerns general to the majority of biomaterials, issues relating to the effect of the implant on the body. While this is vitally important, another consideration exists: namely, the particulars of the shape memory transition.

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2.3.1. Selection of transition temperatures The importance of phases was discussed previously with an emphasis on the resulting mechanical properties. However, the transition between varying phases is important for another reason: it is the transformation between these phases that gives rise to the SME. The temperature above which an alloy exists entirely in the high-temperature phase is known as the b-transus temperature, which in SMAs is also known as the austenite nish temperature (Af). This makes up, along with As (the temperature at which the austenitic phase starts to form on heating), Ms (at which the martensitic phase starts to form on cooling) and Mf (at which the sample is completely martensitic), the four characteristic temperatures that dene the SME. These can be controlled via the concentration of the alloying elements, with the exact effect being a function of the alloying elements electronic properties, as discussed earlier. Ideally, the alloy should be designed to exhibit the characteristic transition temperatures in a region at or near room temperature. This can be seen for a number of reasons: rst, if the Af is too far above the ambient temperature, the applied stress necessary to induce the transformation may be greater than the plastic deformation limit of the b-phase, resulting in unrecoverable deformation. Further, if the Af is at room temperature, then the sample will exist fully in the high-temperature phase at body temperature a requirement for the highly desirable superelasticity. Finally, if the Mf is near room temperature, the sample can be easily cooled into a martensitic form to suppress the superelasticity. Uses of this include allowing a compressed implant to be delivered to the desired location and then deployed in situ as the body warms the implant [1]. Conveniently, the requirements for a near-room-temperature transition and in vivo superelasticity are much the same as those for a low Youngs modulus: a composition such that the alloy exists just above the b-transus. As might be expected from consideration of the action of b-stabilizers, the proximity of an alloy to the transus line relates to the transition temperature. As the b-transus represents the point at which the material exists entirely in the b-phase, it is equivalent to Af; it follows that the further above the transus an alloys composition sits, the higher its transition temperature; likewise, the lower the transition temperature, the further below the transus it sits. 2.3.2. Relationship between transition and recoverable strain In addition to the transition temperature, it is also necessary to consider the recoverable strain that the SMA can achieve. Part of nitinols success is due to the large recoverable strain demonstrated in the martensite to austenite transition, on the order of 10.5% for the monoclinic B19 martensite to cubic B2 austenite [70]. In other SMAs the phases, and hence the degree of recoverable strain, are different. In general, more highly recoverable strains up to 5% are associated with orthorhombic (a00 , as distinct from the hexagonal a and a0 ) or monoclinic martensite, and minimal strains with the uncommon trigonal (e.g. R-phase) and tetragonal systems [70,71]. Another martensite phase, the hexagonal x, may also contribute to the thermo-elastic behaviour of Ti-based alloys. While unequivocal evidence for the SME is scarce in the literature, it has been proposed as the mechanism for a TiMo SMA demonstrating 3.0% recoverable strain [72], and possibly as contributing to the impressive deformation capabilities of gum metal [72,73]. Unfortunately, precipitation of x-phase is also noted to greatly increase brittleness [74], and there are conicting reports on whether the phase can act to inhibit the more desirable ba00 transition [73,75,76]. The x-phase predominantly forms in one of three ways: in low solute alloys, such that the alloy is only just able to retain some b-phase at room temperature, rapid quenching will yield some degree of x-phase as well; as the degree of b

stabilization increases, x-phase will cease to form during quenching, only arising after ageing at temperatures up to 500 C, and fully reverting to a on further ageing; and nally, it is also possible to form the x-phase through deformation at room temperature [55,74,75]. Of these causes, the rst is mostly irrelevant; any alloy sufciently stabilized to lie above the b-transus is by denition stabilized enough that quenching should not form the x-phase. The second method is more concerning; ageing is often a vital step for the renement of the SME, with training of SMAs involving repeated heating up to temperatures of 500 C. Further, those alloys that are predicted to yield the lowest modulus also correspond to alloys at which the isothermal x-phase is more stable than the a-phase [57]. It is thus likely that those alloys are also the most susceptible to undesirable x-phase precipitation. Finally, the formation of x-phase during room temperature deformation is also troublesome; much of the value of an SMA lies in its response to deformation. As the Ti(Nb,Ta)Zr alloy system has demonstrated stress-induced x precipitation before [7779], it is probable that a high M d will also cause such precipitation. Given the disagreement over the inuence of x-phase on SMAs, this does not rule out this particular system as unsuitable, though it does raise concerns. 2.4. Manufacturing methods Having selected for the biomedical, mechanical and thermoelastic properties of the material, it is then necessary to determine the method of production. In this regard, a number of options are possible. These are outlined briey below. 2.4.1. Traditional manufacturing methods Perhaps the most simple, conceptually, is a homogeneous sample of the desired alloy composition, which may be formed via a complete melt of all the components. The resulting alloy can then be either cast directly into the desired shape, or wrought and machined from a more generic billet or ingot. Unfortunately there are several issues with this method, foremost of which is the high melting point of Ti and those elements suitable for alloying; for example, Ti melts at 1668 C, Ta at 3017 C, Nb at 2477 C and Ru at 2334 C [34]. The cost associated with assuring a complete melt is substantial, and is further compounded by the process of forming the desired shape; due to a range of factors, including the reactivity of Ti when hot, the poor heat conduction and the low modulus, the machining of the various grades of titanium is significantly more difcult than of most steels. Attempting to avoid excessive machining via a near-net-shape method (i.e. a method by which the nal product requires only minimal additional modication from the process product) such as casting is somewhat successful, though again the reactivity of the alloy leads to some difculties [55]. This method is also unsuitable for the formation of porous alloys, again due to the high temperature and reactivity of the molten Ti [50,80]. These problems serve to prevent the use of self-foaming or gas-injection methods that have been successful in other metals such as Mg, Zn and Al [50]. 2.4.2. Powder metallurgy methods Powder metallurgy (PM) is another mature production method, and yields a number of signicant advantages over the more traditional methods. To an even greater degree than casting, PM is a near-net-shape process, reducing the need for expensive machining and nishing [55]. Broadly speaking, PM falls into two main categories, the rst of which, blended elemental (BE) PM, utilizes pure powders of the component elements. These are cold pressed (CP) either mechanically or isostatically via gas/uid pressure into the desired shape, this green shape being vacuum sintered to

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produce an end product with a density that is 9599% of that of the cast metal. This method is cheap, simple and versatile, with sintering temperatures being far lower than the melting points of the constituent elements. A prime example is the successful formation of a porous TiTaSn alloy via BE PM, which was sintered at 1200 C, less than half the melting point of Ta by Li et al. [81]. The second category utilizes pre-alloyed (PA) powders, which are produced already exhibiting the desired composition. PA PM is predominantly employed for critical roles with higher mechanical requirements then BE, and as such tends to eschew basic CP techniques for processes like vacuum hot pressing (VHP), hot isostatic pressing (HIP) or a combination of CP and HIP (CHIP). Of the two, BE products tend to exhibit good tensile strengths and fracture toughness, and inhibited fatigue crack propagation, albeit with a reduction in fatigue strength. By comparison, PA PM yields an end product with near full density, and mechanical properties equal to or exceeding those of an equivalent wrought sample, including fatigue strength [55]. Another advantage of the PM methods is the numerous options for producing highly porous samples. While most metallurgical applications target relatively high densities, porosities as high as 50% are theoretically achievable simply through the careful control of powder morphologies and the degree of compaction, with porosities commonly ranging from 5% to 37% [50,69]. However, due to the relatively low degree of compression, the inter-particle connectivity is poor. Therefore, sintered metal powders tend to exhibit poor mechanical properties, lacking toughness, being brittle and being prone to fatigue crack propagation at low stresses [50]. Improved mechanical properties can be obtained by mixing the BE or PA powders with space-holding particles that can later be removed. This is known to produce samples with porosities that can exceed 70%, and can be undertaken with minimal changes to the manufacturing infrastructure beyond standard BE powder processing. This yields a simple and cost-effective method for producing high-quality, highly interconnected porous metals, so long as suitable care is paid to ensuring the complete evaporation of the space-lling element. While a range of llers may be used, those that decompose (such as NH4HCO3) or evaporate (for example, metallic Mg) easily are preferable [50,62,81,82]. Fig. 4 shows a porous Ti sample produced using an NH4HCO3 ller. A third method, gas entrapment, is also possible. In this method, the powder is loaded into a can (often of the same material as the powder), which is subsequently lled with an inert gas under 3 5 atm pressure and subjected to HIP. During post-pressing annealing, the gas expands outward, yielding an up to 50% porous sample sandwiched between solid skins. Despite using much of the same equipment as existing methods, this particular method is poorly suited for biomedical implants; the process is relatively expensive and the solid outer layer prevents osseointegration, one of the primary benets of porous biomaterials [80,82]. Machining this outer layer is possible, but will lead to an increase in cost.

A nal PM method that demonstrably yields highly porous samples is combustion synthesis. In this method, a mixture of metal powders is allowed to react in an exothermic manner. This reaction can be induced by either uniformly heating the can until the bulk of the powder reacts simultaneously, or igniting a specic point with the resulting reaction propagating through the powder. This is also called self-propagating high-temperature synthesis. The release of adsorbed gases along with the evaporation or melting of impurity phases often leads to a violent expulsion of impurities. As a result, combustion PM can produce extremely pure porous alloys, and has successfully done so in intermetallic alloys such as TiAl, TiNi and NbAl [83,84]. However, this method is poorly suited for alloying refractory elements such as Ta, Nb, Hf or Zr with Ti. These metals all commonly act as reducing agents in the reaction, and hence have an insufcient reaction enthalpy to allow practical application of combustion synthesis. 2.4.3. Spray forming methods The spray forming has seen widespread application. This involves the formation of a desired shape by the successive spray deposition of a powder or molten mist. This broad denition can be broken down into a number of ner distinctions, with methods such as plasma spraying being well suited to the deposition of porous materials onto a solid substrate, demonstrating an ability to yield samples with graded porosities and mechanical properties approaching that of PM products [50,55,67,85]. Despite this, a number of issues remain to be addressed. Contamination is common, with oxygen or other impurity phases greatly degrading the mechanical properties of the material. The pores are closed cell, and there are concerns that the method cannot yield complex shapes with uniform mechanical properties both within and between production runs. Due to losses during spraying, machining and sample testing, the process also suffers from a large degree of material wastage. While these issues may eventually be overcome, at present spray forming is unable to match the benets of PM [50,55,85]. 3. Conclusion This review has sought to identify suitable materials for a novel biocompatible SMA. While further testing will always be necessary, the elements titanium, gold, tin, tantalum, niobium, ruthenium and zirconium all display excellent biocompatibility. Hafnium and rhenium have also displayed suitable properties, but it is felt that, due to the relatively limited degree of research on their biological effect, further assessment of their in vivo behaviour is necessary before they can be condently labelled biocompatible. Of those elements deemed biocompatible or potentially so, tantalum, niobium, zirconium, hafnium and rhenium represent the bulk of any alloying species beyond titanium, due to their isomorphous alloying behaviour. These elements are also considered particularly appropriate to yielding an alloy that is well suited to orthopaedic implantation: an alloy system of the form Ti (Ta,Nb)(Zr,Hf), with a high Zr or Hf content as well as suitable Ta or Nb such that the alloy exists near the b-transus, should exhibit an extremely low Youngs modulus. This will hopefully approach that of cortical bone, thereby negating the issue of stress shielding. However, there is some degree of concern over this systems susceptibility to x-phase precipitation, which may have adverse effects on both the Youngs modulus and the shape memory properties. While other alloy systems may be selected to reduce the likelihood of x-phase, these are likely to exhibit a higher modulus. This can be overcome, however, by forming the alloy into a porous structure; while it can adversely affect fatigue life and passivation

Fig. 4. Porous Ti foam via the space-holder method.

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