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Acta Biomaterialia 4 (2008) 447–467

www.elsevier.com/locate/actabiomat

Review

Critical overview of Nitinol surfaces and their modifications

for medical applications
S. Shabalovskaya a,b,*, J. Anderegg b, J. Van Humbeeck a
a
Katholieke Universiteit Leuven, MTM Kasteelpark Arenberg 44, B-3001 Leuven, Belgium
b
Ames Laboratory, Ames, IA 50011, USA

Received 18 July 2007; received in revised form 16 November 2007; accepted 10 January 2008
Available online 6 February 2008

Abstract

Nitinol, a group of nearly equiatomic shape memory and superelastic NiTi alloys, is being extensively explored for medical applica-
tions. Release of Ni in the human body, a potential problem with Nitinol implant devices, has stimulated a great deal of research on its
surface modifications and coatings. In order to use any of the developed surfaces in implant designs, it is important to understand
whether they really have advantages over bare Nitinol. This paper overviews the current situation, discusses the advantages and disad-
vantages of new surfaces as well as the limitations of the studies performed. It presents a comprehensive analysis of surface topography,
chemistry, corrosion behavior, nickel release and biological responses to Nitinol surfaces modified mechanically or using such methods as
etching in acids and alkaline solutions, electropolishing, heat and ion beam treatments, boiling in water and autoclaving, conventional
and ion plasma implantations, laser melting and bioactive coating deposition. The analysis demonstrates that the presently developed
surfaces vary in thickness from a few nanometers to micrometers, and that they can effectively prevent Ni release if the surface integrity
is maintained under strain and if no Ni-enriched sub-layers are present. Whether it is appropriate to use various low temperature pre-
treatment protocols (6160 °C) developed originally for pure titanium for Nitinol surface modifications and coatings is also discussed.
The importance of selection of original Nitinol surfaces with regard to the performance of coatings and comparative performance of
controls in the studies is emphasized. Considering the obvious advantages of bare Nitinol surfaces for superelastic implants, details
of their preparation are also outlined.
Ó 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords: Nitinol; Surface modifications; Biocompatibility; Corrosion; Ni release

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
2. Bare Nitinol surfaces and their modifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
2.1. Mechanically modified surfaces and biological responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
2.2. Chemically and electrochemically modified surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450
2.3. Heat-treated surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
2.4. Biological responses to bare Nitinol surfaces modified using heat treatments, chemical and electrochemical approaches 453
2.4.1. Endothelial and smooth muscle cell responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
2.4.2. Thrombogenic potential, protein adsorption and platelet adhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455

*
Corresponding author. Address: Ames Laboratory-DOE, Room 324, Wiehelm Hall, Ames, IA 50011, USA.
E-mail addresses: svetinol@yahoo.com, shabalóv@ameslab.gov (S. Shabalovskaya).

1742-7061/$ - see front matter Ó 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.actbio.2008.01.013
448 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467

3. Surface modifications with ion and energy sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457

3.1. Conventional ion implantation and electron beam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
3.2. Plasma immersion ion implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
3.2.1. Oxygen implantation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
3.2.2. Diamond-like carbon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459
3.2.3. Biological responses to plasma ion immersion implanted surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
3.3. Laser surface melting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
4. Other surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
4.1. Sol–gel and hydrogen peroxide surface treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
4.2. Bioactive surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
5. Nitinol surface under strain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
6. Conclusions and outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465

1. Introduction diffusion on the interfaces makes this situation even more

Surface modification and coating of Nitinol (an acro-
nym for NiTi Naval Ordnance Laboratory), a family of
nearly equiatomic NiTi alloys with shape memory and
superelastic properties, is a subject of numerous recent
studies directed at improving the material’s corrosion resis-
tance as well as its biocompatibility through elimination of
Ni from the surface. This chemical element is known to be
allergenic and toxic, though essential for the human body.
Although it has been shown that the amount of Ni recov-
ered in biological studies in vitro may be either very low
from the beginning or drop to undetectable levels after a
brief exposure to biological environments [1,2], ‘the nickel
case’ keeps reappearing. Thus, the recent results obtained
on commercial ready-to-use orthodontic wires showed that
the Ni release varied in a wide range from 0.2 to 7 lg cm2
[3]. Moreover, it has been reported that the Ni release can
actually significantly increase with time [4–7], maintaining
a high level up to 8 weeks and even for a few months
[6,7], indicating the need for better understanding of the
material/surface interface. Based on the number of pub-
lished papers on Nitinol surfaces, especially recently, one
might conclude that this issue indeed deserves serious
attention. Various techniques and protocols have been
used for surface treatments; among them mechanical and
electrochemical treatments, chemical etching, heat treat-
ments, conventional and plasma ion immersion implanta-
tion, laser and electron-beam irradiation, design of
bioactive surfaces, and a proper technique can easily be lost
in that jungle of publications. Some of the procedures that
were developed originally for pure Ti and their application
to NiTi not only may not bring any improvement but,
rather, can cause surface damage because of inevitable Ni
involvement. Mechanisms of oxide formation on NiTi sur-
faces vary, depending on media, temperature and irradia-
tion. The interpretations of the Ti and Ni elemental
depth profiles in Nitinol differ because of the possibility
of preferential sputtering of one of the alloy components
that depends on the angles and energies of sputtering ion
beams [8]. The absence of a precise description of atomic
complex.
An interesting development is that X-ray photoelectron
spectroscopy (XPS) and Auger spectroscopy have become
routine methods, and most of the recently published stud-
ies on Nitinol have been done with an impressive list of
techniques, including even energy dispersive X-ray spec-
troscopy (EDS) [3,9–11], unsuitable for surface analysis.
Despite a great number of new publications, some of which
include detailed XPS surface studies, their analyses are very
difficult especially when relevant to biological responses.
Thus, instead of providing absolute values of elemental
concentrations for Ni and Ti, various relative values are
presented that do not give objective information on Nitinol
surface chemistry. The important experimental details such
as the Ar ion sputtering rates, the electron escape angles
associated with a certain surface depth in XPS studies,
the scanning rates in cyclic potential polarization, etc. are
quite often missing. Because the selected scanning rates in
potentiodynamic (PD) cyclic potential polarization are
sometimes as much as 3–30 times higher [12–14] than those
recommended by the American Society for Testing and
Materials (ASTM) for testing medical devices [15], the
results obtained might easily be overrated, especially with
regard to localized corrosion resistance. Very little or no
attention has been paid thus far to the selection of the ori-
ginal NiTi surfaces subjected to modification. As a result,
the surfaces developed either did not perform in the way
in which they were expected to, or their performance was
overestimated because it was compared with the poorest
bare Nitinol surfaces. Sometimes surface modification
techniques are combined with procedures employed for
the design of optimal shape memory and superelasticity.
The consequence is that not only is the surface composition
modified, but so also is the bulk of Nitinol; as a result,
important parameters for medical applications such as
shape recovery temperatures and mechanical properties
are altered.
All the studies of surface modifications of Nitinol have
been aimed at improving its corrosion behavior. It has been
shown that localized corrosion resistance of bare Nitinol
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
may vary significantly, depending on its surface state [7,16–
18]. In PD and potentiostatic (PS) potential polarization,
Nitinol surfaces prepared appropriately do not break or
pit up to 800 mV and even 1300 mV applied potentials.
However, in scratch corrosion tests when surface damage
is caused mechanically, the repassivation ability of Nitinol
happens to be inferior to that of pure Ti, though compara-
ble with the scratch healing ability of stainless steel. The
pitting potentials of NiTi determined in scratch tests are
low (from 150 to 300 mV) compared with PD and PS
polarization, and this is the problem to be targeted in the
development of Nitinol surface modifications.
The present review analyzes the current situation with
Nitinol surface modifications and its progress during the
past 7 years. Earlier publications on this subject have
been covered in previous reviews [18,19], and more
detailed information on Nitinol biocompatibility is pre-
sented elsewhere [20]. The advantages and disadvantages
of the surfaces developed and the limitations of the stud-
ies conducted are discussed, and the surface performances
in Ni release, corrosion and biocompatibility are com-
pared. For the reasons mentioned above, when analyzing
the chemistry of bare Nitinol surfaces, the authors will
often refer to their own papers on XPS studies, which
were conducted at surface-sensitive angles and provided
the actual elemental concentrations pertinent to biological
responses.
2. Bare Nitinol surfaces and their modifications
2.1. Mechanically modified surfaces and biological responses
Traditional surface treatments for biomaterials include
mechanical polishing (Mp), electropolishing (Ep), chemical
etching (Ce) in acid solutions, heat treatments (Ht) under
various conditions, sandblasting and short pinning.
Because of its proprietary nature, information on Nitinol
surface treatments typically is not disclosed. It will be dem-
onstrated in the following sections that, in the absence of
standard surface treatment protocols for Nitinol, mechan-
ically ground or ‘polished-to-luster’ surfaces are often used
in biological studies as well as for coating substrates. These
surfaces, however, are known for their poor reproducibility
in corrosion resistance [16,21], and their biological perfor-
mance is inferior to that of the surfaces additionally treated
[22,23]. The elemental composition of Mp surfaces (1 lm
finish) depends on the sample polishing, cleaning and han-
dling procedures. The total concentration of surface con-
taminants such as Ca, Na, Mg, Si, P and Cl, originating
from polishing or cleaning solutions or from calcium pow-
dered gloves, varied from 1 to 8 at.%, thus affecting the
concentrations of metals on the surface. The Ni concentra-
tions in the 1–4 at.% and Ti in the 8–13 at.% ranges deter-
mined by XPS analysis at a 20° surface-sensitive angle are
reported in Refs. [24,25]. The rest are mostly carbon and
oxygen, the inevitable surface components. It follows from
the literature analysis that Mp surfaces with a contamina-
449
tion level significantly higher than that mentioned above
(30 at.%) are also used in the studies [2].
One of the reasons behind the inconsistent corrosion
performance of Mp surfaces could be the presence of resid-
ual defective surface layers induced, for instance, by elec-
tro-discharge machining (EDM). It was demonstrated
that EDM caused a 5–22-lm-thick melting zone, 50% of
which consisted of TiC [26]. The resulting internal stresses
generated cracks descending from the melting zone into the
depth, as well as propagating in the direction parallel to the
surface.
Additional factors contributing to the inconsistent cor-
rosion behavior of Mp surfaces could be the residual plas-
tic deformation associated with grinding, the inevitable
scratches left by hard inclusion particles emerging from
the Nitinol surface, as well as the chemical heterogeneity
of these surfaces inheriting all inclusions from the bulk of
the material. The biological performances of Mp surfaces
can also be compromised by alteration of surface topogra-
phy due to martensitic relief induced during grinding and
polishing (Fig. 1). Because of these and possibly other,
not yet understood, causes, visually smooth but intrinsi-
cally defective Nitinol surfaces prepared by mechanical
polishing may not be an optimal option either for controls
in the surface studies or for coating substrates.
Sandblasting, shot peening and grooving of NiTi sur-
faces were used to induce specific topography and rough-
ness in order to facilitate cell adhesion, proliferation and
migration [27–29]. Aiming at faster endothelialization of
endovascular prostheses and healing process after implan-
tation, the response of endothelial cells (EC) to surface
grooving was explored [29]. It was shown that grooved
Fig. 1 Topography of NiTi samples mechanically polished (1 lm finish) in
austenitic phase at room temperature as observed in atomic force
microscopy (AFM). Stress caused by mechanical polishing induced
martensitic transformation and surface relief. Four grains of different
orientation are visible as well as inclusions (with bright tips), some of
which are located near the grain boundaries.
450 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
NiTi surfaces promoted migration of EC, up to 64.6%
(p < 0.0001) when compared with smooth controls. The
cells aligned with the grooves elongated and became more
numerous on grooved surfaces. The almost doubled migra-
tion rates of EC upon NiTi surface grooving were observed
as compared with metallic surfaces ordinarily used for
endovascular stents and yet, the proliferative cell response,
equally important to the endothelialization, was not inves-
tigated. It was shown, however, that the ability of the
smooth electropolished NiTi surface and that of the
mechanically polished 600 grit finish (Mp600) to affect
EC were different [22]. The Mp600 surfaces noticeably sup-
pressed cells by 30%, compared with the smoothest elec-
tropolished surfaces and with the controls (as
demonstrated later in this review).
The performance of short peened surfaces was not sta-
tistically different (p < 0.05) from the surfaces polished to
a 1-lm finish in the cytotoxicity and hemolysis tests on
mouse fibroblast [28]. Using human gingival fibroblast cells
and rat calvaria osteoblasts, the authors of Ref. [27] evalu-
ated the effect of different surface roughness induced by
mechanical polishing (80, 400 and 2400 grit finish) on cel-
lular adhesion and maintenance of cellular functions. Inter-
estingly, these two types of cells revealed quite different
patterns in their response to roughness variation. While
the adhesion rates of osteoblasts were not affected by
roughness increase, fibroblast adhesion was reduced signif-
icantly (p > 0.05) on rough NiTi surface (400 grit finish).
The capability for normal growth and proliferation (viabil-
ity) of fibroblasts suffered owing to the effect of roughness
while, on the contrary, osteoblast viability was reduced on
the smoothest surface (2400 grit). As the authors of Ref.
[27] pointed out, the alteration of NiTi surface roughness
on a micron scale showed that there might be a roughness
threshold (between 0.08 and 1 lm) over which fibroblast
proliferation becomes difficult (Fig. 2). However, it is pos-
sible that there also may be a limitation of degree of surface
Fig. 2 Fibroblast and osteoblast viability determined based on MTT assay
(optical density) on 2, 4 and 7 days of culture incubation with NiTi samples
with 400 grit and 2400 grit surface finish. The figure was adapted and
reprinted from Ref. [27] with the permission of IOS Press and the authors.
smoothness, as osteoblast viability was dramatically inhib-
ited by the 2400 grit finish surfaces.
In the case of Nitinol, sandblasting is also employed for
the removal of black surface oxide resulting from the man-
ufacturing process, which involves multiple annealing in
air. This wire is further drawn to obtain a smooth surface
of a light gray color. The fine drawn wires made by this
manufacturing process showed inconsistent corrosion per-
formance [16,30–32], which was attributed to the fact that
the sandblasting was unable to eliminate completely the
original scale on a microscopic level, and also because
the new surface defects were formed during the following
fine drawing of sandblasted wires of irregular surface
topography. As far as the corrosion resistance of as-
received wires under strain is concerned, it did not deterio-
rate when a 4% strain in tension mode was applied [16].
2.2. Chemically and electrochemically modified surfaces
The electrochemistry of Nitinol is poorly explored. Until
recently, there have been no studies on electropolishing and
anodizing of this material. This situation is gradually
improving with the publications of papers on electropolish-
ing processes in various electrolytes [33–36], and anodizing
in various solutions and voltage regimes [14,36]. The effect
of chemical etching (passivation) in HF + HNO3 aqueous
solutions on Nitinol surface chemistry has also been stud-
ied [24,25]. The effect of boiling in water and treatments
in autoclave (hydrothermal treatment) on reducing the Ni
release from NiTi have been explored as well [24,25,37,38].
Electropolishing and chemical etching of Nitinol are
known to be efficient for the elimination of defective sur-
face layers and surface oxidizing. Owing to a gain in total
energy caused by the differences in the enthalpy of forma-
tion of Ti and Ni oxides [39], the preferential oxidation
of Ti on Nitinol surface always occurs. As a result, bare
Nitinol surfaces are built from Ti oxides with Ni concentra-
tions from 2 to 7 at.%, depending on the electrolytes and
regimes employed. Chemical etching and electropolishing
of NiTi can be used for surface structuring as well. As, in
general, Nitinol inclusions tend to be distributed relatively
uniformly in the bulk of the material, their removal during
chemical etching leaves a structured surface that may be
beneficial for cell attachment and locomotion (Fig. 3a).
This could be a better alternative to the grooved surfaces
discussed in the previous section. The electrolytic etching
explored in Ref. [40] induced highly porous NiTi surfaces
that might lead to enhanced Ni release. Surprisingly, elec-
tropolishing of Nitinol can also be used to cause a slight
structuring to promote cell attachment. Originally smooth
surfaces, mechanically polished in austenitic phase at room
temperature and then electropolished in martensite phase
at low temperatures, lose their smoothness and acquire a
step-like structure (Fig. 3d) upon martensitic transforma-
tion [40,41]. This new appearance, called ‘relief’, is due to
the shear nature of Nitinol phase transformation associ-
ated with a uniform shift of atomic planes.
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Fig. 3 SEM images of NiTi surfaces chemically etched in the HF + HNO3
aqueous solutions for (a) wire and (b) disk samples, and electropolished;
(c) Ep1 at room temperature in austenite; (d) Ep2 at low temperatures in
martensite phases. Carbide and oxide inclusion particles can be seen in a
black and white contrast, respectively.
Electropolished surfaces are more heterogeneous than
chemically etched ones because, similarly to Mp surfaces,
they retain all phases inherited from the alloy bulk.
Fig. 3 also illustrates the presence of carbide particles visi-
ble in a black contrast (c and d) and oxide inclusions in
white contrast (b and c). Higher chemical heterogeneity
of Ep surfaces in principle might cause their more inferior
corrosion performance compared with chemically etched
surfaces, especially in a long-term run. The breakdown
potentials reported for cyclically polarized [41,42], Ep, Ce
and CeWb surfaces [17,32,43–45] were in the range from
800 mV to 1400 mV versus SCE. The surface oxide films
obtained after chemical etching and Ep were only a few
nanometers thick [25,34], but most of the Ti was present
only in the oxidized +4 state, though Ni was found in both
oxidized +3 and elemental states [24,25,34]. Oxidation of
Ni and Ti on the surface can be promoted by boiling in
water (Wb) and by autoclaving in steam and water under
pressure [24]. This gentle treatment assisting atomic diffu-
sion, and Ni release into boiling water during treatment
itself, resulted in a thicker oxide film (10–20 nm), a more
stoichiometric oxide composition, a reduced Ni surface
concentration (0–1 at.%), and elimination of Ni release
[38]. An interesting aspect of Nitinol surfaces with thin
oxide layers is the combination of amorphous and nano-
crystalline phases [25,34,45]. The corrosion resistance of
electropolished, Ce and CeWb surfaces did not deteriorate
under the strains of up to 6–8% in tension mode [44,45].
The first evaluations of the anodizing process in Nitinol
indicated that it was different from that reported for pure
451
Ti [14,36]. Although anodizing was employed to generate
thicker oxide films and modify surface topography, no
thick films could be obtained on NiTi in acetic acid electro-
lyte, and in 0.1 M sulfuric acid, as well as in alkaline solu-
tions [14]. In the latter case, a continuous exfoliation of the
anodizing products from the surface occurred. However, in
the acetate and borate buffer solutions, the proper anodiz-
ing conditions were realized, as reported in Ref. [14]. The
resulting 5 lm oxide films had 2 at.% and 7 at.% of Ni on
the surface for the acetate and borate buffers, respectively,
and had amorphous structures. Unfortunately, the anodiz-
ing [14] did not reduce the Ni surface content, and also the
surfaces obtained using an optimized anodizing regime
were heavily cracked. In the PD cyclic potential polariza-
tion, the scanning rate employed was 5 mV s1, i.e., 30-fold
higher than recommended by ASTM standards
(0.167 mV s1) for testing medical devices [15]. As pit initi-
ation is a very slow process, those PD tests may not be sat-
isfactory for the evaluation of localized corrosion
resistance [19,30].
A 10-fold reduction in the Ni surface concentration
(from 3.48 to 0.36 at.%), a similar increase in polarization
resistance up to 3.6 MX, and an order of magnitude lower
current density were registered in the oxide films obtained
upon anodizing of 1 lm finish samples in acetic acid [36].
However, the authors reported on pits when oxide film
thickness reached 20–25 nm. Anodizing in a 0.9% saline
solution using a slow and repeated potential sweeping in
the voltage range of oxygen evolution dramatically
improved the corrosion resistance [41,42,45]. Similar
results were reported also on anodizing in a Na2SO4 solu-
tion [34]. A significant reduction in density of passive cur-
rent, nobler corrosion potentials, and a 10–20-fold increase
in polarization resistance up to 67 MX were observed in the
anodized Ce and CeWb samples. These latter surfaces also
did not exhibit any cracking upon 6% strain in corrosive
solution [45]. This improvement in corrosion performance
upon anodizing was attributed to complete oxidation of
Ni in the external surface layers and partial removal of
inclusions from the surface due to preferential dissolution
of material surrounding inclusions with modified chemical
composition.
2.3. Heat-treated surfaces
Heat treatments of Nitinol in air, argon and partially
reduced atmosphere have been explored again and again
for surface oxidation, aiming at prevention of Ni release
[23,25,34,37,46–49] in the biological environment. It is
important to understand that heat treatments of Nitinol
are also an essential part of alloy processing and device
manufacturing. Temperatures about 700 °C are employed
for wire annealing during its drawing; the temperatures in
a 450–550 °C interval are used to design optimal shape
memory and superelasticity, and for shape setting proce-
dure. Heat treatments at temperatures <300 °C are custom-
arily associated with the processes of modifications of
452 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467

Nitinol surface and are also sometimes employed in the

fabrication of stent grafts for attaching polyester fabric.
Not only may the above heat treatments modify the phase
composition of the bulk, but they also modify the Nitinol
tendencies in formation of either Ti- or Ni-rich surface
sub-layers. The coexistence of various chemical compounds
such as NixTiy with the binary and ternary metal oxides as
well as oxi-carbides in the NiTi surface layers may invite
galvanic corrosion. Ni-rich phases, Ni-enriched matrix
around Ti-based inclusions, as well as free metallic Ni serve
as reservoirs for potential Ni release, especially upon sur-
face damage. Differences in the history of material process-
ing cause both significant variations in Ni surface content
[25] and different patterns in Ni release, discussed in details
elsewhere [20]. Ni accumulated during material processing
in surface sub-layers causes Ni release that is increasing
with time of exposure to corrosive solutions [7], in contrast
to the well-known decrease reported, for instance, in [1,2].
The above-cited surface studies largely disagree as to
the composition of new phases formed during Ht in the
surface sub-layers, most probably because of a different
prehistory of material processing. However, to have a gen-
eral idea of the effect of Ht on Nitinol surface chemistry, it Fig. 4 Typical Ni 2p XPS spectra for NiTi collected at a 20° electron
is worthwhile to analyze at least some of the results. Thus, escape angle. (1) Mp; (2) MpHt (520 °C  20 min); (3) Ep1WbHt; (4)
after oxidation in air at 300–500 °C for only 30 min, TiO, CeWbHt (heat treatments in air); (5) annealed in argon (500 °C  20 min).
pure Ni and NiTi in B2 phase were detected in external Ni in elemental state (peaks at 853 eV and 870 eV) is obvious only for
surface layers at 1° glancing X-ray diffraction (GXRD) Mp surface. The rest of the peaks correspond to a Ni+3 oxidation state
[25].
angle [47]. After oxidation at 600 °C, different phases were
observed: TiO2, Ni and Ni3Ti. Beneath the Ni-rich Ni3Ti
layer, the austenitic B2 and martensitic NiTi phase were (a clear peak in the Ni depth profile) at the sputtering times
present simultaneously (10° GXRD angle) implying an higher than 16,000 s. The accumulation of Ni below the
alteration of shape recovery temperatures of the bulk surface after Ht, however, can be eliminated through preli-
material adjacent to the interface. In agreement with minary chemical etching. The resulting pre-treated surfaces
[47], some free Ni has been reported after Ht at tempera- had a very low Ni surface content <1 at.%; they were
tures of 300–500 °C [23]. Ni concentration increased with depleted of Ni to a depth of up to 90 nm [25], and dem-
the increase in Ht temperature from 300 to 400 °C, prob- onstrated a negligible Ni release [20,22]. The existence of Ni
ably because of the outward Ni diffusion and its accumu- depleted external surface layers was also reported after Ht
lation in the external surface sub-layers. The temperature of Nitinol in a partially reduced oxygen atmosphere
increase up to 600 °C [23] was accompanied by complete [37,48].
surface Ni oxidation (+3) and by a decrease in Ni surface Aiming at medical applications, thin films of NiTi
concentration. Simultaneously, the oxide thickness (10 nm1 lm) obtained by sputtering in amorphous form
increased 20-fold (0.53 lm) compared with the 400 °C and crystallized by annealing (500 °C in a vacuum of
treated samples (0.028 lm) [49]. Fig. 4 shows the degree 106 Torr) were evaluated in the biological assays [50],
of Ni oxidation depending on surface treatment [25]. which will be discussed in the next section.
One can see that Ni in the elemental, non-oxidized state It is appropriate to mention here the structural states of
(a 2p3/2 peak at 853 eV) is obvious only in the Mp sam- the external surface layers resulting from the chemical and
ples (curve 1). The total Ni content is minimal on the sur- heat treatments of Nitinol. The GXRD studies indicate
faces of CeWbHt and the samples annealed in argon that Ti-based oxides are present on Nitinol surfaces in var-
(curves 4,5). ious phase states, namely, amorphous, anatase, rutile and
Fig. 5 illustrates the elemental distribution into the brukite, as it was measured for CuKa radiation at a 0.4°
depth of NiTi surface after Ht at 500 °C and 600 °C in grazing angle [45]. While Ce surfaces are essentially amor-
air [47]; no sputtering rate was reported in the study, how- phous, the heat-treated ones are a mixture of various crys-
ever. It can be seen that the Ni concentration in the exter- tal structures. No attempts have yet been made to clarify
nal surface layers is 8 at.%, i.e., similar to that observed the conditions that would cause the formation of a prefer-
in MpHt samples [25]. The temperature increase up to ential oxide structure.
600 °C induced a Ti oxide film at least 5-fold thicker and The examination of surface topography of all Nitinol
caused accumulation of Ni on the interface with the bulk surfaces that participated in the studies [45,51] revealed a
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467 453

70 surface oxide thickness was in the interval 0.1–10 lm [52].

O1s
Ni2p3/2
However, the oxides with thickness out of this range pro-
60
vided good corrosion protection, though most of them still
cracked on being subjected to 3% deformation. The corro-
Concentration [at. %]

50
Ti2p sion resistance of Ce and Wb wires improved after heat
40 treatment at 500–520 °C for 15–20 min simulating shape
setting procedure. It can be seen from Fig. 7 that the cur-
30 rent density in a passive range of potentials is reduced by
almost two orders of magnitude. Both the increased thick-
20
ness of the oxide film and the elimination of Ni-rich surface
layers through a pre-treatment contributed to the dramatic
10 C1s
improvement observed in corrosion resistance. These sur-
0 faces, however, did not show stable corrosion performance
0 4000 8000 12000
under strain [45].
Sputtering time [s]

2.4. Biological responses to bare Nitinol surfaces modified

70
O1s using heat treatments, chemical and electrochemical
Ni2p3/2 approaches
60

The biocompatibility of porous and non-porous NiTi

Concentration [at. %]

50
Ti2p
for dental, maxillofacial and orthopedic applications is well
40 documented [18–20]. The recent observations related to the
ground and fine finished Nitinol surfaces mentioned in Sec-
30
tion 2.1 of the present review also supports this conclusion.
Thus fibroblastic and osteoblastic cells can adhere, live,
20
proliferate and differentiate themselves on NiTi surfaces
10 [27]. As far as the osteoconductivity of these surfaces is
C1s
concerned, it should be discussed in connection with hemo-
0 compatibility. Quoting from Ref. [53]:
0 10000 20000 30000

Sputtering time [s]
Fig. 5 XPS depth profiles of NiTi heat treated for 30 min in air at (a)
500 °C and (b) 600 °C. A clearly pronounced peak in the Ni depth profile
indicates accumulation of Ni in the internal surface layers [47]. There is
also a small Ni peak (8 at.%) detected in the external surface layers.
gradual increase in crystallinity with heat treatments
(Fig. 6). Thus the size of the nano-crystals increased from
2 nm (Ce and CeWb) to 20–30 nm upon heat treatment,
together with surface roughness [51]. In fact, the CeWb sur-
faces (Fig. 6b) look smoother than Ce (Fig. 6a) because of
uniform growth of nano-crystals filling all the surface cav-
ities. Except for occasional elevations and high frequency
noise, the Ce finish state did not show any crystalline
growth. The detected noise, however, was steady and per-
fectly reproducible. The authors believe that this signal dis-
turbance in the case of Ce surface was due to electrostatic
interaction between the negatively charged phosphorus
dipped tip and a Nitinol surface which is not sufficiently
passivated. Modification of the tip with non-ionic or posi-
tively charged elements (in progress) would help to verify
electrostatic nature of this interaction.
It should be emphasized that the effect of heat treat-
ments on Nitinol corrosion resistance depends on the state
of the original surface subjected to Ht and the thickness of
the resulting oxide films. For example, Ep wires exhibited
severe deterioration in corrosion resistance after Ht if their
The wound site is fist occupied by a blood clot. Connec-
tive tissue cells migrate through the remnants of the clot
still attached to the implant surface, which will have
been modified by both ion and protein exchange mech-
anisms as well as blood-borne cell activities, and the cel-
lular and humoral components of blood, such as
platelets and fibrinogen, will have been already inter-
acted with the implant surface before osteogenic cells
invade the wound site.
A lot of experience and knowledge have been accumu-
lated in the rapidly developing area of application of super-
elastic stents for treatment of diseased blood vessels.
The issues related to Nitinol stent biocompatibility and
their failures were discussed recently elsewhere [20]. Two
major clinical complications with endovascular stents and
stent grafts are subacute stent thrombosis and neointimal
proliferation, which lead to restenosis. Restenosis is defined
as a repeated narrowing of operated blood vessels with
>50% luminal closure. Based on clinical studies, restenosis
rates range from 8% to 10% for ideal lesions, and up to 30–
50% for complex conditions, or associated pathologies [54].
Although the exact mechanisms of thrombosis and resteno-
sis are still being investigated, both involve activation of a
blood coagulation cascade – that is, activation of platelets
and their aggregation through binding to fibrinogen
adsorbed to the implant surface. The activated platelets
release a growth factor (a potential stimulator of smooth
454 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Fig. 6 Topography of various NiTi surfaces: (a) chemically etched (Ce); (b) chemically etched and boiled in water for 20 min (CeWb); (c) additionally heat
treated at 500 °C for 20 min (CeWbHt). Adapted and reprinted from Ref. [51].
Fig. 7 PD cyclic polarization for CeWb (lower curve) and CeWbHt NiTi
disk samples. The drop in the current at the potentials >1.2 V is related to
oxygen evolution. SEM evaluation indicated no traces of pitting after
corrosion testing [41,45].
muscle cell (SMC) proliferation), which results in intimal
hyperplasia. From the objective of preventing extensive
proliferation of SMC, fast stent endothelialization is bene-
ficial [29].
2.4.1. Endothelial and smooth muscle cell responses
Bare Nitinol surfaces were evaluated in a number of
recent biocompatibility studies [22,23,28,50,55]. In order
to be able to compare the biological performances of differ-
ent surfaces, the inevitable subtle differences in sample
preparation and testing techniques should be avoided. This
can be done effectively only within a single study. The
responses of human vascular endothelial cells (HMVEC)
to the surfaces Ht at various temperatures (300, 400 and
600 °C  30 min) were compared with 1 lm finish surfaces
[23]. In turn, the performance of the latter surface was com-
pared with that of Ep, Ht (400 and 600 °C  30 min) and
shot peened in the studies on hemocompatibility [28].
And a more complete set of surfaces that included Mp,
Ce, CeWb, Ht, and surfaces electropolished, in austenite
and martensite phases, was investigated in [22]. All surfaces
evaluated in the latter study caused a very low Ni release
(0–11 ng ml1 per 1 cm2 of the sample surface area) into
the biological medium for human vascular EC and induced
no, or only a mild toxic, effect on these cells (Fig. 8).
The comparative proliferation and migration of
HMVEC and SMC on amorphous and crystalline surfaces
of Nitinol thin films was evaluated in another study [50].
The fact that EC and SMC attached to NiTi thin films
and proliferated in the absence of plasma proteins [50] is
also an indication of the absence of material toxicity. It
has also been shown that SMC proliferated significantly
more slowly than EC but migrated faster. Another interest-
ing observation from this study was that crystalline films
somehow promoted SMC migration compared with amor-
phous state. Comparing the cell proliferation rates, the
authors of Ref. [50] concluded that EC proliferated faster
on crystalline surfaces than on amorphous ones. However,
the corresponding standard deviations were overlapping,
and no statistical analysis was provided. It is worth men-
tioning that SMC attached and proliferated exclusively
along the expandable mesh of NiTi film with no contact
with smooth glass, thus pointing to the importance of
directing cell locomotion.
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467 455

140 400

Adsorbed fibrinogen (ng / cm2)

Relative toxicity, %

120 a
350 ab
100 300
80 bc
bc
250
60 c c
200 c c c
c
40
150
20
100
0
50
b

1
p

2
e

n
bH
eW

Ep
Ep
M

flo
eW

Te
C

0
C

t
00

Ti

ss
e

Au
μm
bH

N
pH
eW

Ep
Ep
C

la
p6
Fig. 8 Toxicity of Nitinol surfaces to the HMVEC based on mitochon-

p1
eW

G
C
M

M
C
drial succinic dehydrogenase (SDH) activity compared with negative Sample group
control Teflon. Surface designations: Mp, mechanically polished 600 grit
finish; Ce, etched in 1HF + 4HNO3 aqueous solution; CeWb, additionally Fig. 9 Fibrinogen adsorption to various NiTi surfaces compared with
boiled in distilled water for 30 min; CeWbHt, additional heat treatment at pure Ni and Ti, and with positive controls gold (Au) and glass. Only two
520 °C for 15 min, mimicking shape setting procedure; Ep1 and Ep2, distinct sample groups ‘a’ and ‘c’ can be selected (p < 0.05). The sample
electropolished in austenite phase at room temperature and in martensite groups labeled ‘ab’ and ‘bc’ can be equally assigned to either group [22,51].
at T = 45 °C. There is only a mild toxic effect observed on Mp (600 grit
finish) and Ce samples (p < 0.05) [22].
tion between increased crystallinity in the row of the Ce,
CeWb and CeWbHt surfaces depicted in Fig. 6 and adsorp-
In another study [23], it was shown that Mp and MpHt tion of fibrinogen (from 150 to 300 ng cm2) seems to be
surfaces (at 300, 400 and 600 °C) altered the patterns of evident. Also, a link between fibrinogen adsorption and
immunostaining and increased EC permeability, resulting Ti surface concentration was established (Fig. 10). For
in reduced epithelium inertness. The oxidative stress levels example, a NiTi surface with the maximal Ti content of
of EC varied with the least damage (170%) caused by 22 at.% adsorbed the highest fibrinogen amount, equal
MpHt (600 °C) samples, and the most damage (270%), to that of pure Ti. Further investigation into chemical
compared with control gelatine (100%), was caused by and electrochemical surface properties [20,45] suggested
Mp samples. that the amount of adsorbed fibrinogen is correlated with
open circuit potentials (OCP), and thus also with surface
2.4.2. Thrombogenic potential, protein adsorption and charge [58]. Thus, as the negative charge on a Nitinol sur-
platelet adhesion face increases (i.e., more negative OCP), fibrinogen adsorp-
Controversies exist in the literature regarding the throm- tion decreases proportionately. It is worthwhile mentioning
bogenic potential of bare Nitinol surfaces. One group of here the electrostatic disturbance detected on Ce samples
researchers provided data from an ex vivo study indicating (Fig. 6a), which also belong to group c (p < 0.05) of the
that Nitinol was significantly less thrombogenic than stain-
less steel [55], while another group found that stainless steel
has the lowest thrombogenicity among metals and alloys
[56]. These controversies may be related to differences in
Nitinol surface chemistry and topography that result from
various surface treatment protocols. It should be men-
tioned that in the study [55] aimed at clarifying this impor-
tant issue, the sterilization procedures employed for NiTi
and stainless steel were different: ethylene oxide and ‘c ster-
ilization’, respectively. It is known by now that the effect of
sterilization on Nitinol surface chemistry can be as power-
ful as that of surface treatment itself [19,24,57]; and for this
reason sterilization is, in fact, a final surface treatment.
In a study on serum protein adsorption [20,22], fibrino-
gen adsorption to Nitinol surfaces varied in a wide range
from 130 to 300 ng cm2 (Fig. 9), suggesting that Nitinol
may have variable thrombogenic potential. Albumin
adsorption was significantly lower. Interestingly, surfaces Fig. 10 Fibrinogen adsorption to various bare NiTi surfaces and OCP
Ep in different electrolytes differed by as much as twice in plotted vs Ti surface concentrations (Mp600 finish, 5.7; Mp1lm, 10;
albumin adsorption, which also suggests a possibility in Ep2, 13; Ep1 and Ce, 15, CeWb, 16.1; MpHt, 18.9; CeWbHt, 21.6 at.% Ti)
[22,51]. With the exception of highly defective surfaces (Mp600 grit finish),
the manipulation of Nitinol thrombogenicity. No obvious
fibrinogen amounts found on NiTi are in direct proportion to the Ti
correlations between protein adsorption and surface concentrations. A correlation between adsorbed fibrinogen and OCP
roughness or oxide thickness within the whole complex of indicates that a gradual alteration in surface charge governs fibrinogen
the studied surfaces were revealed. However, the connec- adsorption.
456 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Ó Wiley Periodicals, Inc 2003
Fig. 11 Percentage of platelets in the spread state on each type of NiTi
surfaces. POL, polished (1 lm finish); EP, electropolished; HT400,30 and
HT600,30, heat treated for 30 min at 400 and 600 °C, respectively; 316 L,
polished stainless steel; Ti, polished Ti; TCP, tissue culture plastic control.
The percentage of spread platelets varied significantly (p < 0.05) [28].
Reproduced by permission from the authors and publisher.
Nitinol surfaces with the lowest amount of fibrinogen
absorbed (Fig. 9).
Protein adsorption to NiTi alloys has also been studied
by Michiardi et al. [59], and it was deduced that albumin
adsorption was directly proportional to the polar compo-
nent of surface energy and inversely proportional to the
concentration of Ni in the bulk alloy. This latter varied
only within 1 at.% (49.5–50.5 at.% Ni), and it is not clear
for the moment how this very small difference in Ni con-
centration within the bulk of the alloys could affect the
Ni surface content.
It was previously hypothesized that the presence of Ni
on a surface may encourage adsorption of albumin to NiTi
[18,22], as albumin is known for its affinity to Ni [60]. The
results on albumin adsorption to Nitinol wires with vari-
able Ni surface concentrations [61] seem to support this
hypothesis.
In a study on NiTi hemocompatibility [28], Mp and Ep
surfaces revealed a twofold higher percentage of spread
platelets than MpHt samples heated at 400 °C (Fig. 11).
And the platelet spreading was completely eliminated after
Fig. 12 SEM images of human platelets adhered to NiTi surfaces [22]: (a) Ce; (b) CeWb; (c) CeWbHt. Sample designation the same as in Fig. 8. Secondary
platelets deposited on a thin base layer of fully spread platelets alter their morphology from (a) round to (b) spread dendritic. Finally, thrombus-like
structures were observed on CeWbHt surfaces when secondary platelets were trapped by the sticky patches of the base layer after Ht (c). (a) and (b) show
that human platelets can form a monolayer of fully spread cells on NiTi surfaces that is considered to be important for the clinical biocompatibility of
implants [62].
the Ht at 600 °C. The reduced platelet activation upon Ht
was attributed in that study to a lower Ni release due to the
binding of elemental Ni into compounds such as Ni(OH)2.
This assumption, nevertheless, needs to be proven through
the estimation of actual Ni release. Moreover, it is not
entirely clear at the moment whether a complete absence
of fully spread platelets is an advantage or disadvantage
of Ht surfaces, as the importance of a monolayer of fully
spread platelets for clinical compatibility of a biomaterial
has been shown [62].
In agreement with Armitage et al. [28], platelet spread-
ing and aggregation on Nitinol varied, depending on sur-
face treatments [20,22,51]. Thus, fully spread platelets
forming a base layer (Fig. 12) coexist with non-activated
round platelets in the case of Ce samples (a); with activated
platelets in a spread dendritic state for Ce and boiled in
water samples (CeWb) as well as EP samples (b); and with
platelets that aggregated in thrombi (c) after heat treatment
(CeWbHt). The Ni content in the above-mentioned
sequence of surfaces decreased from 7 to 2.2 at
0.9 at.%, pointing to a possible link between higher Ni sur-
face concentration and lower Nitinol thrombogenicity.
There is another important factor that must be consid-
ered in this discussion – an alteration in surface topogra-
phy. As one can see from Fig. 12, the major features of
the surface topography on a micron scale induced by chem-
ical etching (crater-like indentions) are preserved after boil-
ing in water and heat treatment. However, on the nano-
scale there are dramatic differences associated with the
growth and development of nano-crystal structure
(Fig. 6). The size of the nano-crystals is increased upon
heat treatment from 2 nm (Ce and CeWb) to 20–30 nm.
The growth of nano-crystals caused a gradual increase in
the surface area available for protein adsorption. This
topography alteration could not affect platelet adhesion
directly because the new surface features introduced were
of nano-scale and the platelets’s diameter in their resting
state is 3 lm. The increase in surface area (caused by
nano-crystalline growth) within the same original surface
topography (Ce) resulted in a gradual increase in fibrino-
gen adsorption in the sequence of the surfaces Ce, CeWb
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
and CeWbHt (Fig. 9) and subsequent platelet adhesion and
activation (Fig. 12). The activated platelets released cyto-
kines which, in turn, activated other platelets, which were
not directly in contact with the surface and caused cell
aggregation in thrombi (Fig. 12c). In agreement with these
observations on Nitinol, it was shown for pure Ti that
increasing complexity of the surface microstructure
enhanced platelet activation both at the implant surface
and in the bulk compartment (not directly on the surface)
[53]. It was also demonstrated that surface topography
had a greater impact than oxide thickness on most cellular
reactions involved with leukocyte adhesion [63], and the
conditions for healing or rejection of implants can be set
out during the first hours of implantation when leukocyte
adhesion to surfaces is increased.
Pure titanium and its alloys are widely used in the ortho-
pedic and dental industries as endosseous implants, which
achieve endosseous integration and enable load transfer
from implant to bone. The higher thrombogenicity of Ti-
based materials such as TiN and TiNbZr [64] compared
with stainless steel is regarded as their advantage because
of the important role that activated platelets play in early
wound healing events, recruiting other cells into healing
compartment through a variety of platelet derived cyto-
kines and intracellular signaling. These signals guide migra-
tion of osteogenic cells towards the implant surface,
improving osteointegration. Similar considerations are true
for Nitinol surfaces.
The whole spectrum of morphological shapes of plate-
lets observed on bare Nitinol surfaces, including round,
pseudopodial, platelet aggregation and also full spreading
provide surfaces that may be suitable for various needs,
from non-thrombogenic to high-thrombogenic. It is impor-
tant to note that while stent applications rely on the non-
thrombogenicity of Nitinol, its use for occlusion devices
requires, in fact, enhanced thrombogenicity [65], which is
achieved currently through the use of polyester textile fab-
ric incorporated into implant devices. It is clear from the
analysis that the selection of an appropriate surface treat-
ment for Nitinol could eliminate the use of fabric associ-
ated with chronic inflammation and also simplify implant
design.
Based on the presented analysis of in vitro studies, it is
obvious that the mentioned disagreements regarding the
thrombogenicity of Nitinol [55,56], are due to its variable
thrombogenic potential that depends on surface chemistry.
The in vivo results of recent animal and clinical studies
reviewed in Ref. [20] showed that the biological perfor-
mances of various bare Nitinol implant devices were simi-
lar to or better than that of stainless steel [65–67].
Concluding this section, it should be emphasized that
bare Nitinol surfaces can be designed with an impressive
array of topographies, desirable oxide thickness, various
chemistry and corrosion resistance, and biological proper-
ties suitable for all types of implantation. To improve both
the immediate response to Nitinol implantation and also
long-term implant performance, it is necessarily, however,
457
to understand its biological properties better, in particular
the specifics of the interactions of Nitinol surfaces with
plasma proteins and platelets. Deeper insight into the elec-
tronic structure of Nitinol surface oxides, their conductiv-
ity/reactivity, nano-structure and defects (oxygen
vacancies and Ti d-band occupancy), surface charge and
oxide stoichiometry is needed. It is also possible that the
catalytic nature of Nitinol surface elements, Ni and Ti,
and their oxides may contribute to the biological responses.
So far, there is ‘progress’ only in the evaluation of surface
compositions of Nitinol which, however, together with the
corresponding surface treatments, were not disclosed in
most of the available studies. In spite of this, there is real
progress because the important correlations between bio-
logical responses and surface energy, topography and elec-
trochemical properties were revealed. This first evidence
has already given important clues to understanding the
hemocompatibility and osteoconductivity of Nitinol
surfaces.
3. Surface modifications with ion and energy sources
3.1. Conventional ion implantation and electron beam
Conventional ion implantation is a line-of-sight process
in which ions are extracted from plasma, accelerated, and
bombarded into a device. In the case of a non-planar
device, manipulation is required to implant all its sides uni-
formly. This adds complexity, which is exacerbated by the
need to provide adequate heat sinks to limit the rise in tem-
perature during implantation [68].
A systematic study of the effects of the implantation of
ions of oxygen (O), carbon (C), copper (Cu), zinc (Zn), zir-
conium (Zr) and molybdenum (Mo), and of electron-beam
irradiation on Nitinol surface chemistry and its mechanical
and shape memory properties for medical applications was
conducted recently [69]. The pulsed electron-beam modi-
fied the surface as deep as 5 nm, exceeding the beam pen-
etration three to four times. The implantation of oxygen
and carbon altered the material to a depth of 20–30 nm.
The thickness of surface layers formed after implantation
of Cu, Ti, Zr and Mo ions also varied. Thus, the implanta-
tion of Zr resulted in 15% increase in Zr concentration at
a depth of 20 nm, as well as in a Ti depletion with its min-
imal concentration at 30 nm below the surface (Fig. 13). It
is interesting that, despite the relatively low implantation
temperatures (150–200 °C), the shapes of the Ti and Ni
depth profiles observed after Zr implantation were similar
to those obtained after heat treatments at 600 °C
(Fig. 5b). Both the electron-beam irradiation and the ion
implantation lead to a depletion of Ni at Nitinol surfaces.
The analysis of phase composition performed using
GIXRD revealed that the modified layers were the complex
composites of both carbides and oxides of implanted ions
and the secondary phases of Ni–Ti or Ni–Ti–Me. For
instance, the Ti implantation (1.4  1017 cm2 flux)
induced Ti-rich phases on the interface with the bulk at a
458 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Fig. 13 Elemental Auger depth profiles for NiTi surface implanted with
Zr. The distribution of Ti and Ni into surface depth is similar to that
observed on heat-treated samples in Fig. 5b. The peaks in the Zr (20 nm)
and Ni (33 nm) depth profiles indicate an accumulation of these elements
in the surface, and a minimum in the Ti depth profile (30 nm) implies
depletion. Adapted and reproduced by permission from the authors [70].
depth of 200–300 nm (70%NiTi(B2) + 20%(Ti2Ni and
Ti4Ni2O) + 10%TiC). The implantation of Zr, however,
induced additionally Ni-rich phases at a depth of
1–1.5 lm (40% NiTi(B2) + 20%(Ti2Ni + Ti4Ni2O) +
610%ZrO2 + 30%(Ni3Zr + Ni11Zr9) + 5%TiC). As one
can see, depending on the type of implanted ions, either
Ni- or Ti-rich phases can be formed in the surface depth.
Although the employed methods altered NiTi surface com-
position to a depth of 1.5 lm, they did not cause deteri-
oration of the shape memory effect, which could be
attributed to the samples being massive. However, the
mechanical properties, the regularities in accumulation
and recovery of martensitic (superelastic) and the plastic
deformations were affected. The shape recovery tempera-
tures were slightly shifted to lower temperatures by 10°
in the implanted alloy and by 30° in the electron-beam-
treated alloys. The corrosion performance of the modified
surfaces in the strain-free state improved, and Ni release
was significantly reduced as compared with the original
Ep state. However, the relaxation of internal stresses
induced, for example, by electron-beam irradiation, pro-
ceeded through surface cracking when loads within elastic
limits (<1%) were applied.
The study discussed [69] did not explore the issue on sur-
face amorphization pertinent to surface hardening and fric-
tion coefficient lowering (i.e., higher resistance to wear).
From the earlier studies aimed at biomedical applications
[70], it followed, however, that the nitrogen implantation
with the doses in excess of 1015 ions cm2 induced amor-
phous regions within both martensitic and austenitic sam-
ples. A similar amorphization effect was observed upon
short peening of the NiTi surface with no detectable influ-
ence on the transformation temperatures, as measured by
differential scanning calorimetry [70]. In both cases, amor-
phization was attributed to the introduction of lattice
defects due to either plastic deformation (peening) or ion
displacement (implantation). No further development of
this issue in connection with medical applications was
undertaken.
3.2. Plasma immersion ion implantation
In plasma immersion ion implantation (PIII), a device is
placed directly in ion plasma and then pulse-biased to high
negative potentials. As a plasma sheath is formed around
the entire device, the ions bombard all sides of the device
uniformly, in contrast to conventional ion implantation.
However, at the high fluencies needed for most material
processing applications (1016–1017 atoms cm2), the com-
petition between ion implantation and sputtering limits
the maximum retained dose, especially in the case of
devices with curved surfaces [68]. A number of papers have
been published recently on the studies of PIII surfaces of
NiTi for medical applications.
3.2.1. Oxygen implantation
The effects of oxygen, nitrogen, argon ion and C2H2
plasmas on surface modification of Nitinol were explored
[71–79,81–84]. PIII carried out at the 20–50 kV target volt-
ages with the incident dose of 1016–1017 atoms cm2,
resulted in the alteration of the chemical composition of
Nitinol surfaces to a depth from a few hundred nanometers
to 2 lm. Although the researchers intended to develop Ni-
free surfaces, the surfaces that emerged from the implanta-
tion were actually enriched with Ni, even though the aver-
age Ni concentration in the external surface layers was 5–
7 at.%. The latter is higher than could be obtained after tra-
ditional surface treatments such as Ce or Ep combined with
a treatment in water or Ht, as shown in Sections 2.2 and
2.3.
The distributions of elements in the surface layers
observed in various studies [71–74] were quite different.
For example, Ni could be accumulated either in external
(15 nm [74] and 80 nm [72]) or in internal surface layers
>1000 nm [71]. The differences in the NiTi substrates used
in the studies (Ar+ sputtered, HF pickled, heat treated, Mp
to luster or ‘shiny’) make the analysis difficult. Some
authors employed heat treatments before implantation
[71], others afterwards [74].
It is appropriate to discuss here the Ar ion sputtering
rates used in the elemental depth profiles. The information
on elemental distribution in external surface layers that is
important for understanding of biological responses is lost
when high sputtering rates P20–30 nm min1 [71,74] are
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
employed in surface studies. This factor has been com-
pletely ignored, however. In most papers, the employed
sputtering rates are not even listed [47,72,73,76,77,79].
Non-destructive XPS depth profiles obtained by means of
variation of electron escape angles in a 15–85° range better
represent the elemental distribution in the external surface
layers 610 nm, because they do not involve preferential ion
sputtering. Additionally, they do not require a calibration
of sputtering rates that would need to adhere to appropri-
ate standards not readily available. To avoid a loss of
information on the external surface layers while studying
thick surfaces, combinations of different sputtering rates
or a combination of non-destructive depth profiling with
Ar ion sputtering can be used.
The analysis of chemical species showed that Ti and Ni
were detected in all possible oxidation states before and
after oxygen implantation, and there was a significant dif-
ference in the depth of oxide location [71]. Thus, in the ori-
ginal CeMpHt state, for example, the oxides were detected
at a depth of 50 nm after implantation. The same oxides
could be found in the deeper surface layers: Ni oxides down
to 30–180 nm, and Ti oxides located even deeper (150–
800 nm). The degree of Ni oxidation also increased after
implantation. TEM studies of the PIII samples showed
that, despite the ‘low’ temperatures involved (Troom =
270 °C [71,73,78]), the phase composition of the material
adjacent to the surface was altered significantly. It was, in
fact, similar to that observed upon conventional implanta-
tion. For instance, in addition to a Ti3Ni4 phase in the ori-
ginal Ht samples, an external TiO2 layer of thickness
800 nm and an adjacent Ti4Ni2O layer of thickness
350 nm were found after PIII [71]. The situation was
quite different when NiTi was not Ht before PII implanta-
tion: instead of the Ti-enriched Ti4Ni2O phase, the Ni-rich
layers constituted from Ni4Ti3 and Ni2Ti phases were bur-
ied within the surface [72].
An important observation is that oxygen PIII might
result in surface damage when doses such as
3  1017 ion cm2 are used [12]. The major advantages of
oxygen implanted surfaces according to the authors
[12,71] were surface smoothing, slightly improved corro-
sion wear, decrease in passive current density and a ten-
dency to pitting. The authors would like to comment that
the conclusion on ‘general improvement of corrosion resis-
tant’ is questionable because the lowest current density in
the passivity region was still detected in untreated samples
[12]. Moreover, the fact that the PIII samples revealed very
low breakdown potentials (200 mV) similar to those of
untreated samples implies that a desirable surface improve-
ment aiming at medical applications was not achieved.
3.2.2. Diamond-like carbon
Due to such properties as extreme hardness, low friction
coefficient, chemical inertness, high corrosion resistance
and excellent biocompatibility, diamond-like carbon
(DLC) coatings are actively under development for various
applications, including prevention of Ni release from NiTi.
459
Various regimes and gases (acetylene C2H2 and benzene
C6H6) are used for PIII, as well as direct coating deposition
with no pulse-biased voltage [76–79,81–84]. It was reported
that direct coating deposition resulted in delamination of
implanted surface layers [81]. To improve DLC film adhe-
sion to metal surfaces, SiC as an interlayer, is used
[5,81,83]. PIII implantation of Nitinol with carbon or nitro-
gen, as well as direct C2H2 plasma deposition, decreased Ni
concentration to a depth of 10–50 nm, especially when
600 °C annealing followed implantation [76,77]. The PIII-
treated samples revealed surface sub-layers enriched with
carbon [76] or nitrogen [75] to a depth of 70–100 nm. As a
result, an undesirable twofold increase in hardness and sig-
nificant alteration in Young’s modulus were observed
[78,79,81]. The modified surfaces showed improved corro-
sion behavior in PD tests and did not breakdown up to
P1100 mV in simulated body fluid [77,78,81,84], while the
controls mechanically polished to mirror had very low Ebd
(230–272 mV). The authors of Ref. [76] pointed out that
‘the surfaces of original samples completely corroded
whereas only 25–30 lm size holes were formed on the
implanted samples’. Although those ‘holes’ cannot be com-
pared with the devastating corrosion demonstrated by the
original surfaces (related to poor surface quality), they still
indicate pitting of PIII-treated Nitinol. Furthermore, the
huge missing areas in the corroded control samples (Fig. 4
in Ref. [76]) point to a significant weight loss; one would
expect high Ti content in the corrosive solution, but it turned
out to be very low. Another important consideration is that
annealing at 600 °C for 5 h employed after PIII is, in fact, an
additional treatment for the bulk and surface of Nitinol. Its
effect should be evaluated separately from the PIII in order to
arrive at appropriate conclusions. The corrosion resistance
of bare Nitinol surfaces similar or better than that obtained
after PIII was reported in a number of studies
[17,32,34,43,85]. It is also questionable whether the
described modified surfaces will retain their stability and
integrity under strain in corrosive environments and whether
they will repassivate upon damage caused by a scratch.
As far as Ni release is concerned, DLC coatings of
1 lm thickness did in fact reduce the Ni release to an
almost undetectable level in the short-term studies [5],
and by a factor of 5 after 6 months. It is important to note,
however, that the Ni release from the original material,
orthodontic wires and cold rolled plates, increased during
a 2-week exposure [5,7,43], contrary to its decrease with
time of exposure reported in Refs. [1,2,45,86]. The different
patterns in the Ni release can be explained by the different
nature of the materials, lab-like alloys vs commercial heav-
ily processed alloys. Ni is always accumulated in the sur-
face sub-layers during Nitinol processing, owing to the
formation of thicker Ti surface oxides, and Ni diffusion
to the surface during those procedures at elevated temper-
atures. Since these Ni-enriched layers were not removed by
machining, etching, etc., they were eventually buried dur-
ing implantation. These buried layers present a potential
source of Ni release in a corrosive environment.
460 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
3.2.3. Biological responses to plasma ion immersion
implanted surfaces
Analysis of biological responses to the PIII-treated sur-
faces [72–79] led to the conclusion that the results are
ambiguous. Thus the total fibrinogen adsorption was
slightly reduced on the DLC and oxygen implanted sam-
ples, but the undesirable denaturated portion of fibrinogen
increased significantly (p < 0.05) compared with the
untreated state [73]. Surprisingly, the increase in the amount
of denaturated fibrinogen did not alter the platelet adhe-
sion. Platelet spreading was reduced on DLC-coated sur-
faces [84] compared with polished controls (1 lm finish),
though the origin of the platelets (human vs. animal) was
not specified. Although in Ref. [84] it was claimed that the
number of platelets adhering to DLC-coated NiTi was
reduced, a statistical analysis to support this conclusion
was not presented. In another study, the activity of alkaline
phosphate, a marker enzyme of mature bone-forming cells,
measured after 7 days exposure did not reveal any statisti-
cally significant differences between the implanted and
non-implanted samples [72]. Further, the evaluation of
death of bovine marrow cells based on LDH release [72]
showed that there was no statistically significant variation
among the following samples: PIII and non-implanted
NiTi, stainless steel (positive control) and pure Ni as nega-
tive control (see information on statistical analysis in the
paper itself [72]). The fact that this test did not distinguish
between the negative and positive controls is of concern.
It should also be admitted that the non-implanted NiTi
samples for biological studies [72] were subjected to a com-
plex protocol with no justifications or evaluation of the
resulting surface chemistry (Ar ion sputtered, sterilized in
steam, pickled in 0.1 M HCl and soaked in PBS).
The conclusion on the cytocompatibility of the PIII-
developed surfaces was based on a study on osteoblasts
[75,77,79]. The results [74,75] displayed in Fig. 14 indicate
that, by the eighth day, the number of viable osteoblasts
exposed to the samples implanted with oxygen was reduced
by 57% compared with the negative control, and the sam-
ples implanted with nitrogen and carbon suppressed osteo-
blast proliferation by 20–25%. In contrast, C2H2
deposition [77] caused 25–45% osteoblast stimulation,
indicating that the response might not be a neutral one.
A slightly better growth of human gingival fibroblasts
was detected on a 1-lm-thick DLC coating compared
with the control untreated orthodontic arch wires [83].
3.3. Laser surface melting
Laser surface melting (LSM) of Nitinol using either
argon or dry air as a shielding gas was explored in Ref.
[2]. Based on XRD measurements (not specified, either
bulk- or surface-sensitive), the authors reported that the
original Mp samples were ‘mainly’ composed of a single
B2 phase (austenite). After LSM in argon, Nitinol revealed
new phases, such as Ti2Ni, TiNi3 and martensite B190 . The
phase composition was different after LSM in dry air, when
30
Number of viable cells (X10000)
NiTi
25
NiTi-N
Ó Wiley Periodicals, Inc. 2005
NiTi-O
20 Empty-well
15
10
5
0
2 4 6 8
Day
Fig. 14 Osteoblast proliferation (p < 0.05) detected on 2, 4, 6 and 8 days
of exposure to NiTi samples (controls, polished to ‘shiny’; N and O
implanted) and ‘empty wells’ – cells with no samples [74,75]. Adapted from
Ref. [74] and reproduced with permission from the authors and publisher.
TiO2 and Ti4Ni2O phases were observed in internal surface
layers. Surprisingly enough, in spite of a surface oxide
thickness of 70 nm, Ni was detected only in the elemental
(non-oxidized) state, and Ti was present in all its chemical
varieties (+2, +3, +4 and 0), implying poor oxidation con-
ditions. The authors wonder whether this could be related
to the heavily contaminated surfaces displaying up to 30%
of Ca, Mg and P.
Despite a great difference in the Ni surface content
between the original (20 at.%) and treated (6 at.%)
states deduced from the depth profiles (Fig. 6 in Ref. [2]),
the difference in Ni release was significant only on the first
day of sample exposure to Hanks’ solution. It was also
shown that, after LSM, the corrosion current in the passiv-
ity region in PD tests could be reduced by two to three
orders of magnitude, similarly to the effect observed on
the heat-treated samples depicted in Fig. 7 in the present
paper. This dramatic improvement was ascribed to the
melting of inclusions, as it had been discussed in [41].
The presence of the B190 martensite after LSM is an indica-
tion of an alteration of chemical composition in the
surface.
4. Other surfaces
4.1. Sol–gel and hydrogen peroxide surface treatments
Attempts were made to form Ti-rich layers on NiTi
through deposition of Ti from various solutions or through
the chemical treatments developed originally for pure Ti
[87–92]. Thus, the sol–gel-derived NiTi surfaces explored
in two studies [88,92] exhibited a satisfactory corrosion
behavior and were depleted of Ni. However, their perfor-
mance was not better than that observed with bare Nitinol
surfaces prepared appropriately. The examination of ele-
mental depth profiles of NiTi [89] treated in 10 M NaOH
aqueous solution (60 °C  24 h) revealed that 30% of
Ni was present on the surface: the amount equal to that
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
of Ti. The Nitinol surfaces with the Ni concentration in this
range caused a toxic effect similar to that of pure Ni [38].
Long exposures of NiTi to temperatures of 60–160 °C in
various chemical environments [4,87,89,90] is fraught with
surface Ni enrichment. A possible alteration of Nitinol
shape recovery temperatures that must be attached to the
body temperature is another consideration.
Oxidation in hydrogen peroxide [90,91] was explored
again for NiTi surface treatments. As was found in [90],
boiling for 2 h in a 30% H2O2 solution resulted in forma-
tion of ‘titania scale relatively depleted in Ni with a
500 nm thickness and some micro-cracks; Ti was present
on the surface as a mixture of oxidation states; Ni oxide
peak could not be found’. The authors also claimed that
their treatment reduced the Ni surface content from 47.5
to 6.7 at.%. It is obvious that the oxide film obtained was
far too thick to keep surface integrity, even without exter-
nal stress applied, and extensive cracking resulted. It is
most surprising, however, that the Ni surface concentra-
tion of 47.5 at.% was reported for a nearly equiatomic
alloy. If it were true, it would be Nitinol with no surface
at all. If the electron escape angle, not specified in the study
performed using VG ESCALAB, were bulk – rather than
surface-sensitive, it could partially explain the striking Ni
surface concentration reported.
Powder immersion reaction assisted coating (PIRAC)
was used for design of a TiN coating [93]. A surface result-
ing from this procedure was composed of two layers, exter-
nal TiN (100–400 nm) and internal TiNi2 (600–1000 nm).
The thickness of these layers varied, depending on the tem-
perature of the PIRAC treatment and was efficient enough
to eliminate the Ni release. However, the PIRAC samples
with thinner coating that may be of interest did not repass-
ivate in cyclic potential polarization, implying a new prob-
lem induced by coating. Thicker coatings improved
localized corrosion performance but not to the level
reported for bare Nitinol with optimized surfaces [16,32].
4.2. Bioactive surfaces
There are continuing efforts in the development of new
NiTi surfaces to ensure their low thrombogenicity [94–96]
as well as the reliable performance of material in orthope-
dics [97–100]. Summarizing the results on the comparative
thrombogenicity study of coated NiTi stents [94], the
authors concluded:
Heparin coating and passivation in HNO3 did not cause
significant effect compared with Mp control stents; mild
reduction in thrombogenicity was observed with Ep,
sandblasted and ceramic coated stents; certain beneficial
effect in the case of polyurethane polymer; and for clin-
ical use, Nitinol stents should be at least electropolished.
In another study of bioactive surfaces [95], an uncoated
NiTi surface (the finish was not specified) performed better
than coated ones. It showed a higher EC coverage, impor-
461
tant for fast endothelialization, as compared with r-hirudin
and heparin-coated stent material. Heparin-coated surface
was unable to sustain EC adhesion even after 48 h of incu-
bation, though heparin immobilization is considered highly
desirable for improved thrombogenicity [101,102]. Here the
authors would like to make a comment regarding polymer
coatings. Despite a beneficial effect of polymer coating on
thrombogenicity observed in [102], and, as we believe, also
on mechanical compatibility with Nitinol superelasticity,
they do degrade in corrosive environments. Additionally,
polymer damage by scratch would uncover a substrate
material, create crevice conditions and thus aggravate cor-
rosion. Moreover, a polymer coating discussed in [94]
exhibits high porosity with the pore size up to 20 lm, per-
fect for crevice. As for the reduction in corrosion rate
claimed in that study, a 30-lm-thick polymer film did result
in its reduction from 275 lm yr1 (bare NiTi surface) to
13 lm yr1 (polymer coated). However, this comparison
with a highly defective 600 grit finish ground surface is
hardly justified. The corrosion rates for bare Nitinol
reported so far are in the range 0.1–2.26 lm yr1 [43,103],
much lower than that of a coated with polymer.
Bare Nitinol surfaces are known for their close appo-
sition to the bone and excellent biocompatibility
[18,19,86]. A Nitinol surface is capable of inducing CaP
layers just from physiological solutions such as Hanks’,
mimicking extracellular body fluids [1]. However, there
are single cases pointing to delayed bone formation,
abnormal bone remodeling, and a little bone/implant
contact even after a few months of NiTi implantation
[104,105]. Although those mentioned cases may be
related to specifics of the material used in those studies
(see discussion in Ref. [20]), there are ongoing studies
on the deposition of highly biocompatible CaP layers
on Nitinol.
Many techniques have been employed for CaP and
hydroxyapatite deposition onto metal surfaces: ion-beam
sputtering, chemical vapor deposition, sol–gel coatings,
electrophoresis, electrochemical deposition and plasma
spraying [82]. The most popular among these is the classi-
cal plasma-spray technique, resulting in NiTi surfaces con-
sisting of rough dense layers of globular particles. This
technique, however, involves thermal stress and is also
not suitable for implants with complex geometry. Chemical
methods such as the dip immersion technique, free of these
disadvantages, are also actively explored. To enhance CaP
deposition onto metal surfaces, preliminary treatments are
employed aiming at designing a TiO2 oxide surface layer.
These pre-treatments combine soaking or boiling in a
30% hydrogen peroxide solution with subsequent soaking
for many hours in KOH or Ca(OH)2 solutions at various
temperatures from room temperature to 160 °C. After this
pre-treatment, the article is soaked for many hours in over-
saturated calcium phosphate solutions, again at elevated
temperatures of up to 160 °C. The resulting precipitating
layers P1 lm thick typically consist of calcium phosphate
with some hydroxyapatite [97–99].
462 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
CaP coating on NiTi obtained using the dip immersion
technique [100] was extensively evaluated in the biological
studies [6]. The Ni release induced by the surfaces emerging
from these studies was very high and lasting, and the bio-
logical responses to those surfaces were rather negative
[6,100,106,107]. The designed surfaces caused activation
and spreading of PMN (polymorphonuclear neutrophile
granulocytes) lymphocyte cells, inhibited apoptosis of
granulocytes and increased expression of intracellular
adhesion molecule ICAM-1. They induced the enhanced
release of inflammatory cytokines (Fig. 15) by the periphe-
ral blood mononuclear cells PBMC (40-fold for TNFa) as
well as by PMN cells compared with an as-received NiTi
and plasma spray coated surface. Based on the results of
a comparative study on cytokine release caused by various
Ni concentrations in the model NiCl2 solutions, the
authors concluded that all the adverse biological responses
were due to specific sharp-edged plate morphology of the
obtained coating. In her dissertation, however, Bogdanski
[6] mentioned the possibility of Nitinol surface enrichment
with Ni, but this possibility was not explored. Since the Ni
release induced by Nitinol surfaces in the studies discussed
was three orders of magnitude higher than the natural Ni
level in the human basal serum, from 1 to 6 ng ml1
[108], we took the liberty of analyzing this case in more
detail.
In contrast to the well-known patterns of Ni release,
when it vanishes after a couple of weeks of exposure of
NiTi samples to biological environments [1,2,20,38,86],
the observed Ni release increased with time (Fig. 16). By
the end of the eighth week, it increased by 50% for both
pre-treated and finally CaP-coated samples. And a very low
Ni release was detected from the as-received samples,
pointing to the effect of the surface pre-treatments
employed in the study. As far as the absolute values are
concerned, the Ni release from the pre-treated NiTi sam-
ples (5000–9000 ng ml1) was at least three orders of
magnitude higher than those observed with bare NiTi sur-
8000
IL-1ra
7000
IL-2
6000 IL-6
IL-8
5000
IL-10
pg/ml
4000 TNF-α
GM-CSF
3000
IFN-γ
2000
1000
0
Control as-received CaP-coated
Fig. 15 Cytokine release by PBMC [106]. From left to right: control cells
alone (no metal samples); cells exposed to NiTi in as-received; and finally
CaP-coated states. Cytokine release for CaP-coated surface is significantly
(p < 0.05) higher than it was observed for the as-received state. Unfor-
tunately, cytokine release for pre-treated surfaces was not evaluated. It
could provide better insight into the nature of cytokine release. Adapted
from Ref. [6] and reproduced with the permission of Bogdanski.
10
9
8
7
Nickel mg/l
6
5
4
3
2
1
0
3 days 1 2 3 4 5 6 7 8
week weeks weeks weeks weeks weeks weeks weeks
Fig. 16 Ni release from NiTi samples into PBS at 7.4 pH measured using
atomic absorption spectroscopy (±1 ng ml1) [6]. From left to right:
etched in alkaline solution mentioned above (pre-treatment for CaP
deposition); finally CaP coated; and as-received states. The lowest Ni
release was detected for as-received samples; it dramatically increased after
surface pre-treatment and was reduced, but not to the original level, when
the CaP coating was deposited. It is obvious that the pre-treatment
protocol employed induced accumulation of Ni on the surface. Adapted
from Ref. [6] and reproduced with the permission of Bogdanski.
faces (0–11 ng ml1), and as much as five times higher than
that in pure Ni samples [22]. It is worth mentioning the
other studies where Ni release also increased with time.
For instance, the absolute values of Ni release detected
after one to a few months exposure [7,43] were at least
1000 times lower than those reported in [6].
The Ni concentrations in the 460–1000 ng ml1 range
induced by bare NiTi surfaces caused only a slight 30%
secretion of inflammatory cytokines interleukin IL 1b and
TNF-alpha by activated monocytes [109]. The Ni concen-
trations of 5000–9000 ng ml1 observed in Ref. [6] fall in
the range of lethal, as defined for the EC [109]. To under-
stand this dramatic Ni release and to demonstrate the chal-
lenge NiTi presents if it is not treat properly, the authors
prepared NiTi surfaces following the protocols for surface
pre-treatment [6,100] and examined the surfaces using
XPS, Auger and SEM, as described in Ref. [25].
The examination of surfaces in SEM revealed an exter-
nal flake-like layer <1 lm thick (Fig. 17a and b) and a
smooth internal layer. The latter became obvious only after
Ar ion sputtering (Fig. 17c). The external rather porous
layer was occasionally cracked, discontinuous and defec-
tive at surface indentions. The internal layer that partially
cleaved by sputtering along the grain boundaries looked
denser. After brief Ar ion etching for only 2 min, the chem-
ical composition averaged from three Auger spectra, such
as those presented in Fig. 18, was C35Ti20Ni12O33 for the
external flake-like surface layer (in agreement with XPS
results) and C8Ti11Ni58O22 for the internal denser layers.
The stoichiometric TiO2 (Ti11O22) composition of the bur-
ied surface sub-layer indicates that the goal of the pre-treat-
ment has been in fact achieved. However, this perfect
stoichiometry also implies that Ni (58 at.%) is present
in the elemental state. At a surface depth <10 nm, both
Ni and Ti were completely oxidized, as followed from
non-destructive XPS depth profiling. Elemental Ni from
the buried surface sub-layers can easily diffuse through
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Fig. 17 SEM images of NiTi surfaces pre-treated by boiling in 30% hydrogen peroxide for 1 h and etching in 4 M KOH at 120 °C for 30 min according to
[6,100]: (a) and (b) represent an external <1 lm Ti-enriched layer; (c) demonstrates splitting of Ni-enriched surface sub-layer after a brief Ar ion etching in
Auger spectrometer.
Fig. 18 Auger N(E) spectra of internal Ni-enriched (1) and external Ti-
based (2) surface sub-layers displayed in Fig. 17.
the external porous Ti-enriched and CaP layers, and release
into biological environments with all associated negative
consequences. The Ni/Ti ratio of 5 induced in the surface
depth of the samples prepared using this routine protocol
developed for pure Ti was twice as high as that detected
upon 22 h exposure to 30% hydrogen peroxide solution
at room temperature [24]. The latter surfaces caused only
a tenfold higher Ni release compared with the original
ones, but they were capable of killing all rat lymphocytes
[38]. Obviously, a very high content of Ni mostly in the ele-
mental state in the internal surface layers of Nitinol sam-
ples resulting from the pre-treatment protocol was
responsible for the enormous Ni release observed in the
study [6] and, at least partially, for the unusual biological
responses mentioned above.
This example demonstrates the importance to the out-
come of the whole coating procedure of the chemical treat-
ments to which NiTi is subjected. Formation of thick
Ti-based external surface layers on NiTi is inevitably
accompanied by Ni enrichment of the underlying sub-lay-
ers. For this reason, the NiTi surface should be either pre-
463
liminarily depleted of Ni, or the oxidation itself must be
less aggressive, allowing for simultaneous release of free
Ni atoms and oxidation of Ti rather than simultaneous oxi-
dation of both Ti and Ni. The temperatures in a 60–160 °C
interval that are employed in various pre-treatment proto-
cols for Ti and also adopted for Nitinol are not high, and
one does not expect significant atomic diffusion, particu-
larly Ni diffusion. Atomic diffusion in the solid state is acti-
vated by introducing vacancies, either through a significant
rise in temperature or due to radiation. In the case of sur-
face oxides, the situation is quite different. Thin Ti-based
oxide layers are forming spontaneously at room tempera-
ture, and Ni atoms are liberated from the Ni–Ti atomic
bonds. The elemental Ni is a lattice defect: an interstitial
atom in the Ti oxide structure. Owing to a smaller size of
Ni atoms compared with Ti and oxygen, Ni can easily dif-
fuse through an interstitial path. However, Ti oxides on
Nitinol surfaces are commonly non-stoichiometric because
of the shortage of oxygen. The sites of missing oxygen
atoms present structural vacancies. These oxygen vacancies
can also be used by Ni atoms to migrate through Ti oxides.
Thus, in the presence of ready-to-use vacancies, the diffu-
sion of Ni atoms occurs effectively, even at low
temperatures.
5. Nitinol surface under strain
Another important issue relevant to the design of Niti-
nol surfaces is the compatibility of new surfaces with the
superelasticity of the material. The strains that the Nitinol
superelastic implant devices are subjected to in the body
may easily reach 3–4% during a cyclic performance within
a superelastic plateau, and they can exceed the superelastic
limit P8% inside catheters during insertion [18]. As indi-
cated in previous sections, bare Nitinol surfaces retained
their integrity and corrosion resistance on being strained
at least to 4–6% [16,45,52], but the behavior of the strained
modified surfaces is still questionable. The mechanical and
corrosion performances of DLC-coated, nitrogen PII-
implanted and titanium-sputtered surfaces were compared
464 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
Fig. 19 SEM images of DLC (a and c) and nitrogen plasma implanted (b
and d) NiTi surfaces. The images (c) and (d) were acquired during
deformation in a tension mode to 3.2% and 5.6% local strains, respec-
tively. Adapted and reprinted from Ref. [44].
with non-coated electropolished NiTi [44,78]. Samples were
strained to 1%, 3% and 5.6% of the local strains in ten-
sion mode within the stress–strain plateau, and above the
plateau to 8%. In contrast to Ep substrate material that
retained an intact surface, the coated surfaces already
began cracking at very low strains (Fig. 19). The first
cracks were observed at 1% strain for nitrogen-implanted
(0.2 lm coating thickness), at 3% for DLC-coated
(0.85 lm) and Ti-sputtered (1.1 lm) surfaces. The evalua-
tion of corrosion resistance in this study showed that, in
contrast to the original bare surface, the coated or modified
NiTi surfaces, already in a strain-free state, might not have
passivity, and their corrosion resistance deteriorated dra-
matically under strain. Alteration of the surface topogra-
phy and heterogeneous distribution of local strains on the
substrate associated with the nature of martensitic phase
transformation (responsible for shape memory effect), as
well as NiTi surface particulates, undermine the adhesion
and cohesion of coatings and lead eventually to coating
disintegration at the strain levels within the superelastic
Nitinol plateau.
6. Conclusions and outlook
From the analysis presented in this review, it is clear that,
using the developed approaches, Nitinol surface can be
modified into various depths from nanometers to microme-
ters, and its coating thickness can be extended up to
30 lm. It is questionable, however, whether micrometer
dimensions are desirable, especially for the thin profile car-
diovascular implants devices where stent wall thickness, for
instance, is being reduced to 30–50 lm to obtain better com-
patibility. Another complication to do with Nitinol is that
certain designed surfaces did not comply with material
superelasticity. Thick surfaces built from native oxides or
resulting from surface modifications and coatings cracked
upon low strains (<1%), and their corrosion resistance dete-
riorated. It is obvious that a final conclusion regarding the
advantages of newly developed surfaces has to be made
based on corrosion tests performed under strain. Finally,
as far as the improvement in Nitinol corrosion resistance
is concerned, the conducted studies of newly developed sur-
faces in their vast majority did not use PS or scratch tests
pertinent to localized corrosion. For this reason, no conclu-
sion can be made on the effect of the analyzed surface mod-
ifications on the Nitinol’s localized corrosion resistance. It
seems at this point that the scratch-healing ability of Niti-
nol, inferior to that of Ti, depends on the nature of the
material, on the concentration, size and volume distribution
of inclusions rather than on the surface oxide.
The reviewed studies indicate that NiTi surfaces as
modified using various procedures that involve tempera-
tures from 160 to 600 °C (heat treatments, conventional
and plasma ion implantation as well as LSM) could be
either depleted of Ni or enriched with it, and, respectively,
surface sub-layers could be composed of either Ti or Ni-
based phases. Segregation of Ni in any form in NiTi sur-
face sub-layers caused by material processing and surface
treatments/pre-treatments or modification should be elim-
inated to ensure non-toxic implant behavior in the body.
The lasting Ni release increasing with time observed in
certain studies is an indication of a Ni enrichment of
the internal surface layers. It is obvious from the analysis
that the long-term exposures to low temperature protocols
(100–160 °C) developed originally for pure Ti are not
suitable for Nitinol because of the inevitable involvement
of Ni.
As follows from the present review, there is obviously a
lack of understanding of the importance of the quality of
the original surfaces subjected to modification. ‘Non-
defined’ NiTi surfaces cannot be used as controls in the
studies, because the meaning of a reference is lost. The
analysis presented does not allow for arriving at definite
conclusions regarding the biocompatibility of the reviewed
surfaces because the corresponding biological studies are
either not available for the moment or not conclusive. In
those cases when the corresponding data were available,
bare Nitinol surfaces seemed to perform better than or at
least similarly to the modified or coated surfaces both
in vitro and in vivo. Considering the important limitations
of artificial surfaces related to their incompatibility with
superelasticity and poor adjustment to various Nitinol sur-
face topographies, further studies into improvement and
optimization of bare surfaces are needed. Chemical and
electrochemical approaches combined with a hydrothermal
approach provided bare surfaces of various topographies
and thickness P20 nm, and resulted in a negligible Ni
release, stable corrosion performance and good/excellent
biological responses. It is obvious from the analysis that
the biological potential of bare Nitinol surfaces is not fully
exhausted. A new aspect of native Nitinol surfaces related
 S. Shabalovskaya et al. / Acta Biomaterialia 4 (2008) 447–467
to the possibility of manipulation with their thrombogenic-
ity pertinent to both cardiovascular and osseogenic implant
devices also merits a deeper insight. It seems at this point
that, for that purpose, many other surface properties
besides surface chemical composition, must be explored
systematically. Among these are: surface oxide hydration
degrees, types of conductivity, surface charge, structure
and possibly catalytic activity of Nitinol surfaces composed
of very well-known catalysts (Ti, Ni and their oxides),
structural defects caused by oxygen deficiency and their
effects on the electronic structure of Ti surface oxides mod-
ified by the presence of Ni.
Acknowledgments
The Research Fund of K.U. Leuven is acknowledged
for financial support. The authors also grateful to L. Meis-
ner, D. Bogdanski, K. Cheung, and C. Hebing, who gener-
ously contributed the materials for this review as well as to
G.K., who volunteered to edit this multidisciplinary ‘pro-
ject’. We also acknowledge the useful discussions with
G. Rondelli and his contribution to this review, as well as
B. Harmon for his constant interest and encouragements.
This manuscript was also authored by Iowa State Univer-
sity of Science and Technology under Contract No. DE-
AC02–07CH11358 with the US Department of Energy.
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