J. Biomedical Science and Engineering, 2010, 3, 1161-1168
doi:10.4236/jbise.2010.312151 Published Online December 2010 (http://www.SciRP.org/journal/jbise/
JBiSE
).
Published Online December 2010 in SciRes. http://www.scirp.org/journal/JBiSE
Production of porous Ni-Ti alloy and test of its
biocompatibility under in-vivo conditions
Ali Kaya Gur1, Nuri Orhan1, Emine Unsaldı2, Ali Said Durmuş2, Neriman Çolakoğlu3
1Department of Metallurgy Education, Technical Education Faculty, Firat University, Elazig, Turkey;
2Department of Surgery, Faculty of Veterinary, Firat University, Elazig, Turkey;
3Histology and Embryology Department, Medical Faculty, Firat University, Elazig, Turkey.
Received 18 August 2010; revised 15 September 2010; accepted 19 September 2010
ABSTRACT
Biomaterials have been out of commonly used mate-
rials in biomedical applications in recent years. To-
day among the mostly-used biocompatible metals are
especially Ni-Ti alloys. For conducting this study,
having extensive usage area in biomedical applica-
tions, Ni and Ti materials were utilized for an alloy
production. Following being mixed using a suitable
mixer at 49Ni/51Ti %wt., the alloy was exposed to
cold pressure of 200 MPa and sintered in a mold. In
addition, the material gained porosity appearance
thanks to usage of the synthesized (SHS) method and
then the final shape of the specimen was taken using
the method of wire electro erosion discharge ma-
chining (WEDM). Afterwards, the specimen was
subjected to the biocompatibility test in in-viv o envi-
ronment by means of on a 3-year-old female dog.
Keywords: Biomaterials; NiTi; Igntion; Implant;
In-Vivo
1. INTRODUCTION
Biomaterials refer to materials which have ever-in-
creasing importance and application areas in every pass-
ing day and are biocompatible, safe and effective, and
also are either natural or artificial origin as well as im-
provement, increase or substitute for the organ, tissue or
body functions 1. Biomaterials science, one of the dis-
ciplines having had great progresses, has exhibited inten-
sive efforts in developing new materials with capability
of adjusting to biological systems when interacting with
the biomedical systems. Used in fulfilling or supporting
the functions of the living tissues belonging to the hu-
man body, biomaterials are either natural or synthetic
materials in contact with body fluids (e.g. blood) per-
manently or at certain intervals. For this reason, the fact
that the material to be implanted to the body fulfills par-
tially or completely the function of the replaced organ in
compliance with the body led to increase importance of
biomaterials and expand their field of study 2.
Because of not fulfilling their functions caused from
various reasons like disease, accidents and old age, some
organs such as kneecap joints, femur, femur head and
vertebrae are replaced with prosthetic materials, needed
to be used at a certain period of time or lifelong in hu-
man body. These prosthetic materials have been studied
by orthopedists [3,4]. Before being used on the body,
biocompatible materials are compared with mechanical
properties of that body part in terms of biomaterials’ raw
material. Compatibility between the problematic area
and the implant to be used is a must. 5.
The materials used as the biomaterial must be strong,
economical and compatible to human body. Depending
on disabilities and various losses of organs, different
materials are used in living organisms. For example,
used as a biomaterial, a synthetic material needs not to
affect the life system in any way in contact with the liv-
ing tissue 6.
Metals and their alloys bear excellent mechanical
properties thanks to their crystal structure and superior
metallic bindings and in return have a great significance
in field of biomaterials. They are utilized in various
fields such as maxillofacial surgery, dental implants, and
cardiovascular surgery as well as joint prostheses and
bone replacement materials in orthopedic applications.
In this respect, among the mostly emphasized issues
related to biomaterial, are the resistance strength, the
fatigue, the surface corrosion, and the allergic reaction
properties to tissues and the biological compatibility 7.
In orthopedic applications titanium is one of biomate-
rial utilized material by courtesy of its properties like
being inert, light-weight, and the ease to produce small
sized specimens besides having the nontoxic structure,

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1162
the antimagnetization, having better mechanical proper-
ties, high biocompatibility, corrosion resistance, and an
elasticity module closer to that of bone 8. NiTi alloys
have the capability of regain their initial shape upon be-
ing heated. This capability is accepted as the shape
memory property 3. Dental bridges, vascular connec-
tions within the skull, muscles for artificial hearts, and
orthopedic prostheses out of biomaterial applications are
benefited from this shape memory property. Because of
its biocompatibility to human body, the porous struc-
ture created in the Ni-Ti alloys with shape memory
property has had an important application area in bio-
medical applications. In case of surgical implantation of
hard tissues, artificial usage of the Ni-Ti alloy on human
body is in question 9.
“NiTi” refers to the alloy composed of Nickel and Ti-
tanium (49Ni/51Ti%) and showing the shape memory
property depending on temperature following occurrence
of deformation. The alloy has congruent compound
structure at 630℃ by 49/51% Ni ratio and turns to liquid
phase at 1310℃ 1 by same ratios. Comparison with
other known metallic materials of today shows that one
of leading alternative material to be used replacing with
natural bone is porous shape memory NiTi alloy [10,11].
Many different techniques are utilized in production of
the NiTi alloy, but the production method with powder
metallurgy out of these techniques comes into promi-
nence due to its favorable characteristics; for example
this method enables easy production for complex-shaped
parts, has controllable initial porosity ratio, lack of ma-
chining after production, display non-occurrence of seg-
regations unlike the products obtained by casting method
[12].
However, during sintering carried out at higher sin-
tering temperatures it is possible to observe anisotropic
changes similar to those occurred in casting method.
Accordingly, it is a necessity for sintering processing,
conducted in order to increase the amount of porosity, to
be performed in a controlled manner and at lower tem-
peratures; otherwise, formation of dimensional changes
is possible. The fact that NiTi based smart materials with
shape memory are benefited in biomedical areas requires
a porous structure derivation, but difficulties encoun-
tered in production of porous NiTi alloy restrict the re-
searches [13]. In terms of biomedical applications, other
important matters are to be capable of controlling the
amount of porosity during production, to obtain the con-
trolled channel widths, and produce more porous materi-
als in addition to identify porosity and channel direc-
tions. 14.
For this study, a porous Ni-Ti alloy was produced and
its usability as an implant material was tested in in-vivo
environment.
2. EXPERIMENTAL MATERIALS AND
METHODS
2.1. Production of Ni-Ti Alloy
In this study, Ni and Ti powders of which chemical
compositions are illustrated in Table 1 were used. The
high purity of the powders used in the study ensures
assurance in terms of biomedical applications and Ti’s
having lower specific gravity will make the implant to
be produced lighter.
Illustrated in Figure 1, Ni-Ti phase diagram is used
for calculation of alloy ratios of the experiment speci-
mens. Creating congruent compound structure at 630℃
by 49/51% Ni ratio, the alloy passes to liquid phase at
1310℃ 1 by same ratios.
Ni and Ti powders were set after having been weighed
at 49/51% Ni ratios on a Scaltec brand scale with 10–5
sensitivity. Following the weighing process, using an
apparatus designed and produced for the mixture process
the powders were mixed at 1500 circulation/min for 20
minutes till obtaining a homogeneous mixture. Figure 2
illustrates the apparatus used for mixture process. The
mixed powders were exposed to cold pressure of 200
MPa in a custom-made mold in Figure 3. Figure 4 il-
lustrates the digital image of the compacted Ni-Ti
specimen.
The pressed specimens were sintered at 250℃ for 30
minutes using a furnace oven with 2℃ temperature sen-
sitivity. Schematic view of the oven is presented in Fig-
ure 5.
In performing the combustion process after sintering,
one direction of the specimens was exposed to the cur-
rent. The combustion in specimens, to which current was
applied, continued to increase until the temperature
reached to the ignition point on the initial surface and
then continued throughout the specimen perpendicular to
the ignition point. The combustion process resulted in
the following exothermic reaction [11,15]:
Table 1. The chemical compositions of Ni and Ti powders.
Materials Purity (%) Powder Dimension (m) Melting Degree (℃) Specific Gravity ( gr/cm3) Alloys Ratio (% wt.)
Ti 98,0  150 1680 4,5 49
Ni 99,5 10 1453 8,9 51

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1163
Figure 1. Ni-Ti phase diagram.
Figure 2. The schematic illustration of apparatus mixing of
NiTi powders.
Ni + Ti  NiTi + 67 kJ/mol,
After the first combustion, the combustion process
continues to occur by itself on a regular basis in the
Figure 3. A Custom-made mold at compacted of the powders
Ni-Ti.
same direction as the initial one. Throughout the speci-
men to which the ignition was applied, the combustion
continued in the same direction and ratio. Figure 6 illus-
trates schematic view of porosity and channel formation

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1164
Figure 4. The digital picture of the compacted Ni-Ti specimen.
in the specimen to which ignition was applied.
The side and top views of the digital images of the
Ni-Ti powders after the ignition are seen in Figure 7.
The ignition occurred from point I to II without inter-
ruption. As seen after the combustion process, proceed-
ing direction of the channels is as parallel to each other
and from the center to outward.
Illustrated in Figure 8, the specimen was processed at
the Fine Sodick A320D – EX21 brand WEDM work-
bench and after having been processed, it was trans-
formed into the status in Figure 8. As seen in Figure 8,
the channels proceeded longitudinal and deeply in the
specimen.
In order to determine the alloy ratios of the produced
alloy, the surface of the material was polished and it was
etched with 10% HF, 5% HNO3 and H2O etchant. After
these process, the images and regional alloy values were
taken using scanning electron microscope (SEM) and
energy dispersive spectrometer (EDS), respectively. The
results of the SEM-EDS values of the produced speci-
men are presented in Figure 9. Upon analysis of the
EDS values and comparison of elementar percentages
with the ones in the literature [11,12], it is seen that the
Figure 5. The schematic illustration at furnace temperature of Ni-Ti powders.
Figure 6. The specimen of ignition applied is seen schematically.

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1165
Figure 7. The digital pictures after the ignition of NiTi.
Figure 8. The digital pictures after the WEDM of NiTi.
roduced specimen perfectly matches with the definition
d implant under
ith intramuscular Ketalar,
(K
f proximal tibias of the dogs were selected for
th
on the dog
and at the end of this duration, the dog was euthanized
p
of the mentioned Ni-Ti alloy.
2.2. Surgical Operations
The biocompatibility test of the produce
in-vivo conditions was performed using a three-year-old
healthy female dog. The experimental animal used in the
study was cared and feed by the European Convention
for the Protection of Vertebrate Animals used for Ex-
perimental and other Specific Purpose of 1996. Experi-
ment was conducted in the Animal Hospital of Veteri-
nary Faculty of the Firat University in Turkey in accor-
dance with general guidelines.
Anesthesia was performed w
etamin hydrochlorur, 50 mg/ml Davis, United King-
dom) injection at 15 mg/kg dose 10 minutes after intra-
muscular Rompun (Xylazine hydrochloride 23.32 mg/
ml, Bayer, Leverkusen/Germany) injection at 3.5 mg/10
kg dose.
Both o
e application, skin incision was performed on the
proximal medial surface of the tibia on the same line as
incision of subcutaneous fascia. A hole of 100 mm in
diameter and 18 mm in depth was drilled at the proximal
metaphysic of the revealed tibia. Figure 10 schemati-
cally illustrates this process. After the produced implant
was placed in this opened hole, the subcutaneous fascia
and the skin were closed with 2/0 number chromic cat-
gut, and 0 number silk thread, respectively.
Two-month clinical examination was made
Figure 9. The results SEM-EDS of NiTi.
Figure 10. The schematic illustration of operation.
applying high-dose intravenous sodium penta-barbita
ing the
plants were taken from the dog and placed in a 10 %
l.
For the histological analyses, bone samples includ
im
formalin solution.

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1166
3. RESULTS
3.1. Atomic Absorption Analysis Results
For atomic absorp
rums were taken f
tion analysis, 10-30-60 day blood se-
rom the dog two times; before the op-
ing these
and ¼
from
ical risk
lant material (Ni-Ti) was
i-Ti alloy is a new type of material in
ructure. As is seen, when
eration (control) and after the operation. Dur
periods, the Ni level was determined by the blood tests
since it is well known that Ni is very toxic in vivo. The
tests were conducted using Atomic Absorption Spec-
trometer (ATI929) device in The Faculty of Science at
Firat University, Department of Chemistry. Table 2 dis-
plays test results of atomic absorption analysis. As seen
in Table 2, the results of the obtained data indicate that
Ni was smaller than 1; that is to say Ni-Ti did not have a
toxic effect on the subject in present form.
3.2. Radiogram and Digitals-SEM Analysis
The radiographic views of the tibia of the subject two
months later after the placement are seen in ½
cross sections and Figure 11 illustrates radiograms
various durations on the tibia.
The test sample was divided into two and thus some
part of the test sample was revealed. This appearance is
presented in Figure 12. SEM images were taken from
the regions marked as 1-2-3-4 and 4-5 in Figure 12. It is
seen from images that each image was taken from dif-
ferent regions in Figure 12. As observed from these im-
ages, formation of a mechanical binding between the
bone tissue and NiTi occurred and no pathological case
was available at these points. Image 12-2 was taken from
the channel on NiTi and a firm bone tissue formation is
observed to have occurred on the tissue NiTi progressing
through the channel. Likewise, the same situation is ob-
served clearly in Figure 12(e).
SEM examinations revealed that bone tissue forma-
tion extended to the pores and the channels formed as a
result of the resorption of NiTi in the implant in the di-
rect proportion with 2-month time (Figure 12(d)). It was
seen that periosteum and bone tissue were formed on the
outer surface of the NiTi implant in the sample (Figures
12(a-d)). In this sample, apart from Havers channels and
lamellar structure, formation of blood vessels is also
seen from SEM images (Figures 12(a-d)). 16
3.3. Pathological Analysis
At the end of the analysis, no pathological cases were
found and also a formation having no patholog
between bone tissue and imp
determined. The endochondral ossification and trabecular
bone (arrow) between the bone tissue and the implant
are distinguished in Figure 13. Hematoxylen eosin x20
(Figure 13).
4. DISCUSSIONS
The Ni-Ti used in the study was produced combining a
bioinert metals (Ni-Ti) with a mechanical binding force
[11,15]. Porous N
terms of its pores’ linear st
Ni-Ti powders are carefully mixed and ignited at suit-
able environment and temperatures, quite symmetrical
structures are formed. When this alloy is used under
in-vivo conditions with its homogenous distribution and
open pore structure, the living tissue is provided to move
through open channels on the sample. Because of their
bioinert structures 11,12, it is possible for Ni-Ti alloys
to be used in in-vivo environment.
As a conclusion, since biomaterials are used on hu-
man body for a period of time or lifetime, properties of
these materials have always been a subject of research
conducted by many researchers. Today, one of the
mostly-studied subjects by modern medicine and bio-
medical engineering is to select, create, or optimize ap-
propriate materials used for treatment of diseases. It is
necessary that the relationship among used materials,
tissues carrying these materials, and the whole organism
be as compatible and healthy as possible. Another neces-
sity for these materials is to have properties to fulfill the
function of the organ which they replaced with as im-
plants. Therefore, considering the human body weight,
the material to be used must resist without losing its co-
ordination at 37℃ and 7.25 pH value, without presenting
an adverse reaction to the tissue in contact, and without
breaking and bending against mechanical forces. In ad-
dition, it is desirable that pores of samples produced as
implants must be interconnected with each other from
three dimensions, that’s to say they must have open po-
rous structures. Therefore, high open porosity lets not
Figure 11. ½ and ¼ cross sections and radiograms after the
placement in the tibia of NiTi sample.

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1167
Table 2. Atomic absorption analysis test result.
Results Sample Volume (ml) Oscillation Absorb Ni Sample Ni (mg/lt)
JBiSE
Before Operation, Control 0,76 1 4
10 Day, Control 0,95 1 3
30 Day, Control 0,86 1 6
60 Day, Control 0,79 1
‹ 0,5
7
Figure 12. The picture SEM of tissue-NiTi implant at inside tibia.
Figure 13. The picture of pathologicaly examination.
only the body fluid penetrate into the implant by making
the tissue move easily in the implant but also soft or hard
tissues penetrate into the implant material, and as a result,
a stable interface occurs. In our study, it was observed
that th
oved in the implant and no pathological cases occurred
between the bone tissue and NiTi sample. In addition,
the fact that Ni and Ti have low specific gravities sup-
ports our study in terms of mechanical aspect. In other
words, the produced implant (NiTi) will be capable of
resisting to mechanical forces without breaking and
bending.
This study indicates that when compared to othe
known metallic materials of today, porous NiTi alloy is
the most important alternative material to be used in-
stead of natural bone. However, in order to reach a con-
clusive result this study should be examined with similar
studies on different test subjects and in different periods,
because researchers are required to make further inves-
tigations on these subjects.
The following study should focus on a hybrid bioma-
terial (Ni-Ti and hydroxyapatite) production combining
the ignition mechanism and the sintering. Utilizing the
resulted reaction temperature and the temperature output
allows materials to be produced economically in powder
metallurgy based Ni-Ti-Cu or other alloys.
he studies related to biomaterial should be on re-
structuring the natural tissues by using the capacity of
healthy
the bio-
e tissue, in which this situation was provided, T
m
body’s renewing itself instead of replacing a
issue with the damaged tissue. For this reason, t
materials to provide restructuring the natural tissues re-
quire to be improved.
5. ACKNOWLEDGEMENTS
In this study was supported by TUBITAK research council (Project No.
r

A. K. Gur et al. / J. Biomedical Science and Engineering 3 (2010) 1161-1168 1168
TUBITAK 2002-K).
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