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Microwave Assisted Calcium Phosphate Coating of Biomedical Implant Materials

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A Thesis
entitled
Microwave Assisted Calcium Phosphate Coating of Biomedical Implant Materials
by
Anthony N. Passero
Submitted to the Graduate Faculty as partial fulfillment of the requirements for the
Master of Science Degree in
Mechanical Engineering
_________________________________________
Dr. Sarit Bhaduri, Committee Chair
_________________________________________
Dr. Hongyan Zhang, Committee Member
_________________________________________
Dr. Ioan Marinescu, Committee Member
_________________________________________
Dr. Patricia R. Komuniecki, Dean
College of Graduate Studies
The University of Toledo
May 2015
ProQuest Number: 10029017
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An Abstract of
Microwave Assisted Calcium Phosphate Coating of Biomedical Implant Materials
by
Anthony N. Passero
Submitted to the Graduate Faculty as partial fulfillment of the requirements for the
Master of Science Degree in
Mechanical Engineering
The University of Toledo
May 2015
This thesis investigates the feasibility of using a novel coating method to coat the
biomedical implant materials polyether ether ketone (PEEK) and nitinol. In the field of
orthopedics, many promising implant materials cannot easily bond directly to the
surrounding bone. PEEK is a polymer which exhibits favorable mechanical properties
and extreme chemical inertness. Nitinol is a nickel-titanium shape memory intermetallic
which can undergo deformation when heated. This allows fixation of surrounding bone
and tissues. While neither material is suitable to use as is, a coating of calcium phosphate
(the primary mineral component of bone) has been shown to promote bone attachment.
Many methods exist for depositing this coating, but the biomimetic method is attractive
for its simplicity and high degree of similarity to actual bone chemistry. A faster
formulation of the biomimetic method using microwave irradiation was used to coat
PEEK and nitinol substrates. This coating was examined using several characterization
methods, including scanning electron microscopy, energy dispersive spectroscopy, X-ray
diffraction, and water contact angle measurements. The coatings exhibited the desired
properties necessary for bone attachment, and warrant further clinical study.
iii
Acknowledgements
I would like to thank my advisor, Dr. Sarit Bhaduri for all his guidance during the
duration of this project. The time and energy he spent is much appreciated. I would also
like to thank my committee members Dr. Hongyan Zhang and Dr. Ioan Marinescu for
their input and participation in this process. I received much assistance from my
laboratory members: Dr. Huan Zhou, Maryam Nabiyouni, Yufu Ren, Elham Babaie,
Niloufar Rostami, Sameh Saleh, and Amitesh Das. Without their support and assistance,
this process would have been nearly impossible.
Last and most importantly, I would like to thank my friends, my family, and my
wife Mrs. Elizabeth Passero. I cannot imagine undertaking this without her support, and I
am truly grateful.
v
Table of Contents
Abstract .............................................................................................................................. iii
Acknowledgements ..............................................................................................................v
Table of Contents ............................................................................................................... vi
List of Tables .................................................................................................................. vii
List of Figures .................................................................................................................. viii
List of Abbreviations ......................................................................................................... ix
1
Introduction
.........................................................................................................1
2
PEEK ………….....................................................................................................22
2.1 Introduction .....................................................................................................22
2.2 Experimental Procedure ..................................................................................25
2.2.1 Material Preparation..........................................................................25
2.2.2 Microwave Assisted Coating ............................................................26
2.2.3 Characterization ................................................................................28
2.3 Results and Discussion ...................................................................................28
2.4 Conclusion ......................................................................................................33
3
Nitinol ………… ...................................................................................................34
3.1 Introduction .....................................................................................................34
3.2 Experimental Procedure ..................................................................................36
3.2.1 Material Preparation..........................................................................36
vi
3.2.2 Microwave Assisted Coating ............................................................37
3.2.3 Characterization ................................................................................38
3.3 Results and Discussion ...................................................................................39
3.4 Conclusion ......................................................................................................42
4
Conclusion…… .....................................................................................................44
References ..........................................................................................................................46
vii
List of Tables
1.1
Calcium Phosphate Coating Methods ......................................................................3
1.2
Alternate Coating Solution Compositions .............................................................15
1.3
Solution Concentration vs Soaking Time ..............................................................19
2.1
PEEK Coating Solution .........................................................................................27
3.1
Nitinol Coating Solution ........................................................................................38
viii
List of Figures
1-1
Plasma Spraying Diagram........................................................................................4
1-2
Dip Coating Diagram ...............................................................................................6
1-3
Sputter Coating Diagram .........................................................................................8
1-4
Electrophoretic Deposition Diagram .......................................................................9
1-5
Laser Ablation Coating Diagram ...........................................................................10
1-6
Sol-gel Deposition Flowchart ................................................................................12
1-7
Titanium Etching and Coating Formation .............................................................16
1-8
Coating formation on CaO-SiO2 Glass ..................................................................17
1-9
Microwave Coating Flowchart ..............................................................................20
2-1
PEEK Visual Comparison......................................................................................29
2-2
PEEK Water Contact Angle...................................................................................30
2-3
PEEK Visual Water Contact Angle Comparison...................................................31
2-4
PEEK XRD Patterns ..............................................................................................31
2-5
PEEK Low Magnification SEM ............................................................................32
2-6
PEEK EDS and High Magnification SEM ............................................................33
3-1
Nitinol Visual Comparison ....................................................................................40
3-2
Nitinol Low Magnification SEM ...........................................................................40
3-3
Nitinol High Magnification SEM ..........................................................................41
3-4
Nitinol Coating Structure and EDS........................................................................42
ix
List of Abbreviations
Ca-P............................Calcium Phosphate
EDS ............................Energy Dispersive Spectroscopy
HA ..............................Hydroxyapatite
PEEK..........................Polyether Ether Ketone
SEM ...........................Scanning Electron Microscopy
XRD ...........................X-ray Diffraction
x
Chapter 1
Introduction
Optimizing the performance of the bone-interface of biomedical implants has
become the subject of significant research, spurred on by the need for bone replacements.
Currently, more than 2 million fractures result from osteoporosis in the United States
alone, and cost more than $19 billion each year [1]. Typically, bone substitution
procedures utilize materials from the patient (autografts), or failing this, natural
substitutes (allografts). This eliminates the possibility of immune-based inflammation,
which can lead to failure of the procedure. Unfortunately, this is not always possible, and
thus the only alternative is to utilize artificial implants with favorable biological
responses. Coating the implant surface with appropriate materials increases the
bioactivity of such an implant, enhancing osseointegration (strong bone-interface).
Although many implant materials are biocompatible and cause no inflammatory
response, the body may recognize the implant as a foreign object and surround it with
fibrous tissues in order to isolate it [2]. This results in a nonmineralized layer between the
implant and surrounding bone, which may be insufficient to rigidly constrain the implant
[3]. It was found by Branemark et al. that careful surgical procedures can minimize the
thickness of this fibrous layer, which is essentially made of scar tissue [4]. When this is
1
achieved, the implant surface attaches directly to the surrounding bone with no
intervening tissues, leading to osseointegration. To anchor the implant even further, true
chemical bonding of bone to implant must be achieved by optimizing the surface
properties of the implant.
Direct bonding with bone can be achieved in the presence of a bioactive calcium
phosphate (Ca-P) coating on the implant surface. A coating is preferred over an implant
made entirely of Ca-P because the bulk mechanical properties of such materials are often
insufficient for typical loadings. Hydroxyapatite (HA), Ca10(PO4)6(OH)2, is the Ca-P
commonly chosen for this purpose because it is the primary mineral component in bone
[1,5-10]. A relatively thin layer of HA on an implant such as titanium thus provides
favorable surface conditions for biocompatibility between the implant and surrounding
tissues without sacrificing the excellent mechanical properties of titanium implants.
Many methods are currently available to provide this Ca-P coating.
Coating procedures may make use of either a physical or chemical process.
Physcial coating methods include Plasma Spraying [11,12], Dip Coating [13-15],
Sputtering [16-20], Electrophoretic Deposition [21-23] and Pulsed Laser Ablation
[24,25]. These and several other methods are shown in Table 1.1. Though very common
in industry, nearly all physical methods are line of sight processes, which can only be
used to coat implants of the simplest geometries. Most processes also utilize high
temperatures, which have been seen to cause thermal degradation of the coatings [2].
This can cause insufficient adhesion to the substrate as well as excessive dissolution, both
of which may lead to premature failure of the implant and the formation of particulate
debris. The generation of high temperatures may also prevent the incorporation of
2
Table 1.1: Various Ca-P coating techniques [26].
Technique
Thermal
spraying
Thickness
30 to 200 µm
Advantages
High deposition rates; low cost
Plasma spraying
30 to 200 µm
High deposition rates; improved wear
and corrosion resistance and
biocompatibility
Magnetron
sputtering
0.5 to 3 µm
Pulsed laser
deposition (laser
ablation)
Ion beam
deposition
Dynamic
mixing method
Dip and spin
coating
Sol-gel
technique
0.05 to 5 µm
Uniform coating thickness on flat
substrates; high purity and high
adhesion; dense pore-free coatings;
excellent coverage of steps and small
features; ability to coat heat-sensitive
substrates
Coatings with crystalline and
amorphous phases; dense and porous
coatings; high adhesive strength
Uniform coating thickness; high
adhesive strength
High adhesive strength
0.05 to 1 µm
0.05 to 1.3 µm
2 µm to 0.5 mm
< 1 µm
Electrophoretic
deposition
0.1 to 2.0 mm
Electrochemical
(cathodic)
deposition
0.05 to 0.5 mm
Biomimetic
process
< 30 µm
Hot isostatic
pressing
0.2 to 2.0 µm
Micro-arc
oxidation
3 to 20 µm
Inexpensive; coatings applied quickly;
can coat complex substrates
Can coat complex shapes; low
processing temperatures; thin coatings;
inexpensive process; can incorporate
biological molecules
Uniform coating thickness; rapid
deposition rates; can coat complex
substrates; can incorporate biological
molecules
Good shape conformity; room
temperature process; uniform coating
thickness; short processing times; can
incorporate biological molecules
Low processing temperatures; can form
bonelike apatite; can coat complex
shapes; can incorporate biological
molecules
Produces dense coatings
Simple, economical and
environmentally friendly coating
technique; suitable for coating of
complex geometries
Disadvantages
Line of sight technique; high temperatures
induce decomposition; rapid cooling produces
amorphous coatings; high temperatures prevent
from simultaneous incorporation of biological
agents
Line of sight technique; high temperatures
induce decomposition; rapid cooling produces
amorphous coatings; high temperatures prevent
from simultaneous incorporation of biological
agents
Line of sight technique; expensive; low
deposition rates; produces amorphous coatings;
high temperatures prevent from simultaneous
incorporation of biological agents
Line of sight technique; expensive; high
temperatures prevent from simultaneous
incorporation of biological agents
Line of sight technique; expensive; produces
amorphous coatings
Line of sight technique; expensive; produces
amorphous coatings
Requires high sintering temperatures; thermal
expansion mismatch
Some processes require controlled atmosphere
processing; expensive raw materials
Difficult to produce crack-free coatings; require
high sintering temperatures
Sometimes stressed coatings are produced,
leading to their poor adhesion with substrate;
requires good control of electrolyte parameters
Time consuming; requires replenishment and a
pH constancy of the simulating solutions
Cannot coat complex substrates; high
temperature required; thermal expansion
mismatch; elastic property differences;
expensive; removal/interaction of encapsulation
material; high temperatures prevent from
simultaneous incorporation of biological agents
Except of calcium orthophosphates, coatings
always contain admixture phases
biological agents into the coating, such as in drug delivery. Furthermore, many substrate
materials with lower melting points simply cannot be used in the presence of such high
temperatures, due to thermal degradation of the substrate itself. While somewhat limited
3
in efficacy by these shortcomings, physical coating processes are quite common and can
be useful in appropriate situations.
Of the processes listed in Table 1.1, plasma spraying is the most commonly
utilized coating process in industrial settings. This process is illustrated in Figure 1-1.
Commercially available plasma spraying equipment first became available as early as the
1960s, supplemented by the technology accompanying the famous “space race” [2]. This
equipment was most commonly used in the aerospace industry, with subsequent research
into its potential application in the biomedical field. The first patent for a plasma-sprayed
HA coating technique appeared in Japan in 1975, and since then the technology has
evolved and seen widespread application [27].
Figure 1-1: Common configuration of the plasma spraying coating methodology for
producing HA coatings [28].
4
The mechanism of plasma spraying first involves the creation of a plasma jet by ionizing
an inert gas (often argon). A powdered HA feed is provided to the system, which is then
melted by the superheated plasma and projected toward the substrate surface. While this
process is able to quickly deposit a very high volume of material, it suffers from
numerous drawbacks common to physical deposition processes, as noted in Table 1.1
[26]. These problems include line of sight deposition and issues related to the extremely
high temperatures used, such as delamination, decomposition, and the inability to
incorporate biological agents. As the core of the plasma jet can reach temperatures as
high as 12,000 K, these temperature-related problems are unavoidable and inherent to the
methodology itself. Nevertheless, plasma spraying provides an efficient means of quickly
producing coatings in certain situations.
Dip coating is another physical coating technique that is of significance. This
coating methodology entails submerging the implant into a sol containing Ca-P [29]. The
samples are then removed at a closely controlled rate, which is a key factor in
determining the coating thickness. This is followed by a heating step used to evaporate all
remaining solvent and further densify the coating. Coating thickness can be increased to
an arbitrary desired thickness by applying subsequent dip treatments over the previouslyformed coatings [13]. The underlying parameter behind this process that allows coating
in this manner is the viscosity of the coating fluid. This, along with the speed at which the
substrates are removed, controls the coating thickness. This process is illustrated in
Figure 1-2. There seems to be some confusion in the literature about the terminology for
dip coating. Perhaps because of its similarity to the biomimetic route of coating
(submersion of substrates into a coating solution), some biomimetic studies have been
5
Figure 1-2: General configuration illustrating the dip coating methodology [30].
labeled as “dip coating” [31]. However, these two coating processes rely on very
different underlying processes and should not be used interchangeably. In dip coating,
previously-formed HA in solution attaches to sample surfaces through physical, rather
than chemical, means. On the other hand, biomimetic coating involves a HA layer being
“built up” ion by ion on the surface of the implant, and is thus categorized as a chemical
method.
When speaking of dip coating, it is important to mention spin coating as well.
Spin coating utilizes a similar underlying mechanism, also employing a solution with
dissolved HA powder. However, instead of submerging substrates into this solution, the
sample (typically a flat disk) is spun at a specific speed and the coating solution is poured
6
onto it. The force of rotation directs the fluid radially outward, with rotation speed and
fluid viscosity determining the resulting thickness [15]. Controlling this rotation speed is
analogous to controlling the removal speed in dip coating. Because dip coating and spin
coating share the same underlying mechanism and are similar in operation, they are on
occasion used interchangeably to refer to one another. While dip/spin coating is quite
simple and inexpensive, it is similar to plasma spraying in that in entails excessively high
temperatures during the heating step following the dipping [14, 15]. These temperatures
are encountered after the coating solution has covered the substrate surface, and are
necessary to evaporate the solvent and densify the final coating. As with plasma spraying,
this can cause several problems, such as delamination, decomposition, and the inability to
incorporate biological molecules.
Sputter coating offers unique advantages in certain areas as compared to other
physical methods, yet still exhibits common problems. The coating process involves the
bombardment of a target with plasma under vacuum conditions. This target is a
compressed powder composed of the coating material [20]. An inert gas, such as argon, is
ionized using a large electric potential difference, and is accelerated to strike this target.
Such a collision scatters atoms of the target throughout the chamber, some of which come
into contact with the substrate and adhere to it. The general layout of the process is
shown in Figure 1-3. It is somewhat unusual among physical coating methods in that
even though it involves high temperatures because of the plasma, these temperatures are
not in direct contact with the substrate. The plasma only contacts the HA target, and
although this prevents incorporation of biological agents, substrates with lower melting
temperatures, such as polymers, can be used [32]. While this demonstrates an advantage
7
Figure 1-3: Illustration of sputtering used to produce thin film coatings [33].
over thermal spraying methods, deposition rates are low and the sputtering targets of
proper chemistry are expensive. Additionally, sputter coating is a line of sight process,
and cannot be used to coat complex geometries. Thus, while sputter coating of HA
remains useful for certain research applications, it is not suitable for widespread
commercial application.
Electrophoretic deposition provides another physical route for producing uniform
coatings on a variety of substrates, including complex substrates. A solution containing
dissolved HA is necessary, similar to that found in dip/spin coating. Two electrodes are
placed in the water, and one is connected to the substrate. This creates an electric
potential gradient in the coating solution, which draws particles to the substrate. This
8
Figure 1-4: Depiction of coating formation by electrophoretic deposition [34].
process is illustrated in Figure 1-4. This method is therefore not line of sight, and any
portion of the substrate that is exposed to the solution can be coated, allowing coating of
complex surfaces [23]. The resulting coating is also quite uniform, owing primarily to the
homogeneous nature of electrical field distribution near the surface of conductors. This is
typically followed by a high temperature sintering step, to further densify the coatings.
Because of this step, many problems common to the physical coating methods are
unfortunately present in electrophoretic coating as well, including the inability to coat
polymers with low melting temperatures. The primary means of controlling the
deposition process is variation of the electric potential between the electrodes, as well as
the particulars of the coating solution (composition, pH, etc.) [21,22]. Careful control of
these parameters allows the deposition of uniform coatings with relatively high purity,
but still suffer from high temperature complications and limitations.
9
Figure 1-5: Schematic of the pulsed laser ablation process [35].
Pulsed laser ablation is a coating method quite similar to sputtering, though
different in some significant ways. As in sputtering, materials are stripped off a target,
usually a flat disc, and travels through a vacuum chamber to nucleate on the substrate.
However, while sputtering distributes the target material throughout the chamber due to
the simple momentum of the collisions of gas ions with the target, the process in laser
ablation is far more complex. Each laser pulse vaporizes a portion of the surface, and the
intense electromagnetic fields of the laser quickly ionize the vaporized target atoms,
forming a plasma jet [36]. The laser ablation process is illustrated in Figure 1-5. Electrons
freed by this are accelerated by these electromagnetic fields and impact the target,
releasing more material. Control of gas pressure during deposition is essential, as once
deposition has begun the plasma jet created by the laser can sputter a portion of the
10
formed coating if the pressure is too low. This process is often referred to as “backsputtering.” Alternately, if the pressure is too high, transfer of the particles to the
substrate is hindered. However, fine tuning of pressure allows a greater rate of deposition
than back-sputtering removal, and net growth occurs [37]. Pulsed laser ablation is a
flexible process in that many different morphologies of coatings can be produced,
including crystalline and amorphous structures [24]. Additionally, it shares the attribute
of superior adhesion with the sputtering process, due to the similar nucleation conditions.
However, it is also quite expensive, is a line of sight process, and due to the high energy
of the laser and formation of a plasma jet, very high temperatures are involved, and
prohibit incorporation of biological molecules [24,25]. Due to these problems, pulsed
laser ablation while useful in some capacities suffers from many shortcomings common
to physical processes, and new coating approaches are needed.
It appears that all physical coating processes employ either a line of sight
deposition or involve high temperatures, and many feature both. To combat these issues,
chemical processes to produce HA coatings such as sol-gel [38-41] and biomimetic
coating [42-46] are used. These are often preceded by a separate chemical treatment to
etch the surface and create appropriate functional groups which induce apatite formation
on the surface. These treatments consist of either an acid [47,48], hydrogen peroxide [4952], anodic oxidation [53-55], or a strong base [56-58], and can even be used on their
own to improve bioactivity of the implant without a Ca-P coating.
Sol-gel deposition is a widely used chemical process for producing high quality
Ca-P coatings. Substrates surfaces are covered with a solution which evolves into a
colloidal gel. This solution usually contains chemicals which combine in solution to
11
Figure 1-6: Flowchart illustrating the various stages of sol-gel deposition [59].
create HA (such as triethyl phosphate and calcium nitrate), which constitutes the solid
phase of the gel [40, 41], but may also contain a powdered form of HA [38]. The solution
can be applied to substrates using principles of dip [40] or spin [41] coating. The sol-gel
process is illustrated in Figure 1-6. To form a coating from this configuration, the liquid
phase must be removed. This is usually accomplished through applying heat (often at 7080°C) and allowing the substrates to dry, leaving behind the solid phase of HA.
Following this, annealing is typically performed at temperatures up to 600°C to further
densify the coating [38, 40, 41]. While this temperature range is quite low when
compared to many physical methods, it is still high enough to preclude the use of several
polymer implant materials. Additionally, the sol-gel process utilizes costly materials, and
12
similar to sputtering deposition, may not always be economical. Nevertheless, sol-gel
deposition offers distinct advantages over many competing processes, such as lower
temperatures and the ability to coat complex substrates.
Many of the preceding coating methodologies offer unique advantages over others
and may be of scientific and, in some cases, industrial interest. However, each process
has associated problems that can be difficult to overcome, depending upon the specifics
of the application. All processes, excepting sputtering, involve temperatures too high to
permit many common polymer substrates, such as polyetheretherketone (PEEK), to be
used as implant substrates. Some of these same processes also involve even higher
temperatures which, in addition to preventing low melting point materials from being
used, also preclude biological molecules for controlled drug release from being used.
Sputtering, however, is not exempt from problems, as it and many other physical
processes are line of sight, and cannot coat complex surfaces. Because biomedical
implants may take on quite complicated shapes, the ability to coat complex surfaces is
highly sought after. Finally, several processes mentioned previously, including sol-gel
deposition and sputtering, either involve expensive materials or require expensive
processing, and for this reason may not be economically viable for industrial application.
Thus, a need exists for an inexpensive method capable of coating complex substrates at
low temperatures. Biomimetic coating provides such a method.
The biomimetic methodology, as the name suggests, seeks to mimic human
physiological conditions to maximize biocompatibility. While replicating every feature of
human physiology down to the cellular level is obviously impossible, selection of key
parameters yields a reasonable approximation. Reproducing the ionic concentrations of
13
human blood plasma, holding the solution at a neutral pH of 7.4, and fixing the
temperature at human body temperature (37°C) provides sufficient conditions for
bonelike HA to form. The coating solution was first introduced by Kokubo et al. and
contained ionic concentrations similar, but not identical, to human blood plasma [60].
These coating solutions are typically formulated so that HA does not spontaneously form
homogenously in solution, which would wastefully deplete the ions needed for coating.
Instead, the solution is constructed to be stable under physiological conditions, but able to
precipitate in very close proximity to the implant surface. Functional groups created by
either alkali treatment or glass particles, as in the original experiment of Kokubo et al.,
lower the solubility of HA in the immediate vicinity of the implant surface, allowing
coating formation [61].
Among the chemical methods, only the biomimetic route offers the attractive
feature of “bonelike” HA [62]. In natural bone, several ionic substitutions are made in the
Ca10(PO4)6(OH)2 structure of HA, often by the carbonate ion, although other substitutions
by magnesium and hydroxide ions can occur [63,64]. Biomimetic coating methods are
able to create HA that contains these substitutions, resulting in bonelike coatings. These
bonelike coatings have been found to exhibit superior biocompatibility with osteoblast
cells when compared to other common methods [46]. Biomimetic coating also features
the advantages of low cost and the ability to coat complex substrates, with the only
drawbacks being related to the extensive coating time required. Thus, coating via
biomimetic methods shows great promise for the future.
Because the coating solution was designed to emulate human body conditions, it
has been termed “simulated body fluid” (SBF). Since its initial formulation, many
14
Table 1.2: Ion concentrations found in several proposed SBF solutions compared with
those found in human blood plasma [65,66].
Concentration (mM)
Ion
Blood
c-SBF
r-SBF
i-SBF
m-SBF
t-SBF
Na+
142.0
142.0
142.0
142.0
142.0
142.0
Cl-
103.0
147.8
103.0
103.0
103.0
125.0
HCO3-
27.0
4.2
27.0
27.0
10.0
27.0
K+
5.0
5.0
5.0
5.0
5.0
5.0
Mg2+
1.5
1.5
1.5
1.0
1.5
1.5
Ca2+
2.5
2.5
2.5
1.6
2.5
2.5
HPO42-
1.0
1.0
1.0
1.0
1.0
1.0
SO42-
0.5
0.5
0.5
0.5
0.5
0.5
alternative solutions have been proposed to replace the original SBF (c-SBF), some again
by Kokubo (r-SBF, i-SBF, and m-SBF) [65] and others (t-SBF) [66]. The ionic
concentrations of these solutions, as well as those of human blood plasma, are shown in
Table 1.2. While all SBF solutions approximate ionic concentrations of blood plasma to a
certain degree, stability is an issue for both r-SBF and i-SBF. These were found to
display significant stability problems after 4 weeks storage at 5°C or 2 weeks storage at
36.5°C [65]. Additionally, Tas developed an SBF solution which more closely models the
Cl- and HCO3- content of blood plasma without sacrificing stability [66]. Higher HCO3-
15
Figure 1-7: HA formation on alkali pretreated Ti surfaces in SBF [4].
content is very important, as bonelike HA contains carbonate substitutions, and therefore
at the present time t-SBF is most attractive for biomimetic coatings.
The coating procedure itself typically consists of immersing alkali pre-treated
substrates in SBF until a coating of sufficient thickness has been formed [45]. Alkali pretreatment forms a hydrous layer on the substrate. For the case of a titanium substrate,
sodium (or potassium) titanate is formed, shown in Figure 1-7 [4]. This layer is necessary
for coating, as soaking in SBF causes the cations in the layer to exchange with H3O+ ions
in the solution, forming hydroxide groups on the surface of the substrate [67]. Originally,
instead of an alkali pre-treatment, Kokubo et al. utilized glass particles placed on the
substrate surface as the cation source, as illustrated in Figure 1-8, though this method has
largely been replaced with alkali pre-treatment [60]. These hydroxide groups increase the
ionic activity of HA in the localized region around the substrate, allowing coating
nucleation without general precipitation and associated loss of ions from solution. This
16
Figure 1-8: HA formation on the surface of CaO-SiO2 glasses in SBF [4].
nucleation is initially amorphous, with particles on the order of nanometers, and can grow
to form larger, crystalline structures after sufficient soaking time in SBF [68].
Biomimetic coating, when compared to more widespread coating methodologies
such as plasma spraying, is relatively new. The few biomimetic studies that have been
performed have indicated promising results. Barrere et al. observed that after
implantation into rats, carbonated apatite coated on titanium calcified into the
surrounding bone and showed no signs of toxicity [69]. This coating exhibited superior
behavior when compared to a biomimetic coating which was not carbonated. The unique
ability of the biomimetic approach to form bonelike, carbonated apatite thus enables
better implant behavior. Kokubo et al. also conducted a biomimetic in vivo study in both
rats and rabbits using the polymer polyethersulphone (PES) as a substrate [61]. All
17
coatings investigated degraded at an acceptable rate for bone growth to extend up to the
bare PES surface with no failures in fixation. Furthermore, by varying the SBF
composition, the crystallinity of the coating can be controlled, and it was seen that this
affects the degradation rate, with amorphous coatings degrading faster than highly
crystalline coatings. Thus, the biomimetic method enables a simple means of adjusting
composition and thereby coating degradation rate to a suitable level for a given
application. Biomimetic results in vivo have shown excellent biocompatibility and offer
unique benefits that other approaches do not, indicating great potential for further
application.
Although biomimetic coating offers many advantages over alternative methods, it
is time consuming, and recent work has focused on constructing timescales feasible for
industrial application. In its original implementation, the biomimetic method used by
Kokubo et al. required approximately 14 days to completely coat the substrate, which is
far too long to be appropriate for industry [60]. In order to decrease the time required for
coating, efforts have been made to increase the concentration of ions in the SBF. The
ionic concentration of each constituent in the SBF can be increased by a factor of five or
even ten, and the time required for coating has drastically been reduced [45, 70]. Table
1.3 shows the required soaking time for various concentrations of SBF. In this manner, it
has been possible to produce a 22 µm thick coating in as little as two hours. One
difficulty associated with increasing SBF concentration is the degree of supersaturation,
as SBF is supersaturated when operating at physiological pH [71]. This can be overcome
by using CO2 bubbling or other buffering agents to adjust the pH to values lower than the
physiological 7.4 when using concentrated forms. Thus, a departure from strictly
18
Table 1.3: Required soaking time to produce a biomimetic coating for various SBF
concentrations [45, 60, 72-75].
SBF Concentration
Required Soaking Time
1.5
14-20 days
4
7 days
5
1-2 days
10
2 hours
physiological conditions such as pH and ionic concentrations allows for a similar but
more practical coating approach.
Work done recently by Bhaduri et al. has modified the biomimetic process by
introducing microwave irradiation, drastically reducing coating times [76]. It was
previously found that in the presence of microwave radiation, amorphous Ca-P nuclei
will form spontaneously in SBF [77, 78]. These amorphous precursors are similar to
those found in the first stages of biomimetic coating. In this coating methodology,
amorphous precursors form throughout the SBF, and those that form on the surface of the
sample can act as nuclei for further crystal growth. The formation of a thin, amorphous
Ca-P coating in this manner is illustrated in Figure 1-9. Because the entire microwave
process takes only a few minutes to complete, it is possible to produce HA coated
substrates extremely quickly, compared to other biomimetic methods. In this way, an
extremely thin HA layer may be formed consisting entirely of amorphous nuclei, or these
nuclei can be used to grow crystals in SBF to any thickness desired. The as-formed
amorphous coating was seen to exhibit favorable biological properties via
19
Figure 1-9: Ca-P formation for conventional biomimetic coating and microwave assisted
biomimetic coating [76].
cytocompatibility tests [76]. Originally performed on titanium substrates, one of the
primary focuses of this work was to investigate the viability of the method for alternative
substrates, such as PEEK and a porous Ti-Ni alloy.
To meet the growing need for biomedical implants, biomimetic coating offers
several key advantages over comparable methods, and shows great promise for the future.
Its philosophy of emulating natural processes honed over countless years by evolution
produces the only coating methodology capable of forming bonelike apatite, by means of
the SBF solution. This variety of apatite has been seen to exhibit superior
biocompatibility, and can be coated onto complex surface geometries and incorporate
biological molecules for applications such as drug delivery. Furthermore, all materials
20
and equipment are very inexpensive, and the only drawback of the entire process is the
lengthy timeframe required for its completion. However, new advances in concentrated
SBF solutions have reduced this to hours, and microwave assisted studies have drastically
reduced even this to mere minutes. The subject of this work is to engineer this microwave
assisted process for other materials such as PEEK and a porous TiNi alloy. The eventual
outcome of this work may at last make the biomimetic process commercially viable for
the orthopedic industry.
21
Chapter 2
PEEK
2.1
Introduction
Calcium phosphate (Ca-P) coatings are often applied to biomedical implant
surfaces in order to allow direct bonding with bone [64]. Known as osseointegration, this
direct bond with no intervening soft tissues allows rigid mechanical fixation, forestalling
failure under loading [3]. While many methods of producing this coating exist, most have
serious drawbacks related to both extremely high temperatures and high cost. The
biomimetic approach overcomes these obstacles and also offers the unique advantage of
being able to produce a bone-like coating: hydroxyapatite (HA), Ca10(PO4)6(OH)2, which
contains various ionic substitutions such as the carbonate ion [67,79]. To achieve this, an
alkali pre-treatment involves submerging substrates, usually titanium, into an acid, base,
or hydrogen peroxide [51,80]. Cations from the particular alkali treatment used (for
example, Na+ in NaOH) form a titanate layer on the surface of the implant [4]. When
subsequently immersed in a simulated body fluid (SBF) this layer causes the formation of
amorphous Ca-P precursors in the immediate vicinity of the implant. These grow into
large crystals as Ca2+ and PO43- ions are consumed from the SBF solution over time [81].
22
The biomimetic coating methodology is thus an attractive means of altering the surface of
an implant to enhance osseointegration.
While biomimetic coating offers several unique advantages, it is a very slow
process in its original form. Recent advances have been able to reduce this timescale
from weeks to hours by increasing the solution concentration [45,60]. While this is a
considerable improvement, even shorter times are required for widespread use in
industry. To this end, Bhaduri et al. have investigated the effect of microwave irradiation
on SBF [77]. It was found that amorphous calcium phosphate (ACP) nanosphere
precursors were formed homogeneously in solution, without further crystal growth. This
precipitation is thought to occur because in SBF under microwave irradiation, ACP is
first to precipitate, followed sequentially by octacalcium phosphate and HA, as stated by
Lerner et al [82]. A bioactive substrate submerged in solution in such a situation will
form ACP precursors completely covering the surface, as performed by Bhaduri et al. on
Ti6Al4V substrates [76]. This microwave-assisted biomimetic coating methodology
allows complete coverage of the substrate by a thin ACP layer in mere minutes.
Polyether ether ketone (PEEK) biomedical implants are a growing class of
implant materials which provide advantages over more traditional materials, such as
titanium. PEEK is a highly inert polymer which was originally utilized in aircraft and
turbine blades due to its strength and high resistance to thermal and chemical degradation
[83]. Following this, it began to be considered for biomedical implant applications in the
late 1980s, for many of the same reasons [84]. In particular, controlling the polymer
fabrication process allows for the adjustment of the elastic modulus to a desired result.
Titanium, the most commonly used implant material, has an elastic modulus as high as
23
ten times that of human bone [85]. Because of this, the bone surrounding the titanium
implant experiences a much lower stress, while the implant experiences a high stress
state; this phenomenon is known as “stress shielding”. This situation is deleterious to the
bone tissue, which is accustomed to a certain level of stress and in the absence of it will
weaken, causing injury [86]. By adjusting the elastic modulus of PEEK to a value
approximately equal to that of bone, this stress shielding can be virtually eliminated.
Additionally, the chemical inertness of PEEK allows acceptance of the implant by the
body, causing no toxicity and minimal inflammation [83,84]. For these reasons, PEEK is
an excellent candidate for study as a biomedical implant material.
The present work aims to investigate the viability of the microwave-assisted
coating methodology for PEEK substrates. This material is extremely inert, and as such it
does not display toxicity, but unfortunately also results in no bioactivity. Thus, alkali
treatment allows for the necessary functional groups to form on the implant surface.
However, because PEEK is so inert, the etching process must be intensified and this work
employs microwave-assisted NaOH etching to this end. PEEK substrates were coated
using microwave-assisted biomimetic deposition, forming an ultra-thin ACP layer
covering the implant surface. If a thicker coating is desired, the as-deposited ACP layer
may be grown in concentrated SBF to the desired thickness, following more conventional
approaches. In this manner the production of bioactive calcium phosphate coatings on
PEEK for biomedical implant application is investigated.
24
2.2
Experimental Procedure
2.2.1 Material Preparation
Cylindrical PEEK rods with a 3/16 inch diameter were purchased from Precision
Punch & Plastics. These rods were cut into 1/10 inch disks in the Mechanical, Industrial,
and Manufacturing Engineering Department at the University of Toledo. The samples
were cleaned ultrasonically in acetone, 70% ethanol, and deionized water for 10 minutes
each, subsequently. Following this, samples were air-dried overnight. All chemicals were
purchased from Fisher Scientific.
An intense alkali pre-treatment is required to form the functional groups
necessary for apatite growth for a material as inert as PEEK. Pino et al. utilized a 48 hour
10 M NaOH treatment to this end, which was also adopted in this study [87,88]. This pretreatment was carried out in a tightly capped bottle stored at approximately 60°C. To
further intensify the etching, a NaOH microwave etching processes was utilized. This
involved subjecting the substrates, immersed in 10 M NaOH solution, to microwave
irradiation for a total of five minutes, on 60% maximum power in a 1200 W microwave
oven (Panasonic). During this process, it was necessary to exchange the samples and
solution between two different glass bottles approximately every 40 seconds, due to
extensive cracking of the glass from overheated evaporated NaOH. Because PEEK is
buoyant in 10 M NaOH, a thin piece of cheesecloth (HDX – Home Depot) was loosely
wrapped around the substrates and weighted down with a small piece of inert alumina
ceramic for both phases of the etching process. To maximize etching time, samples were
25
again stored in tightly capped 10 M NaOH solution at 60°C following microwave etching
until immediately prior to coating (typically fewer than 2 hours).
2.2.2 Microwave Assisted Coating
The coating solution is an SBF with ionic concentrations made to imitate human
blood plasma. However, in the interest of further optimizing coating processes, certain
concentrations have been modified in ways slightly deviating from physiological
conditions. To prepare the coating solution, the following chemicals were dissolved in
approximately 950mL of water in the following order: 1.135g KCl, 27.986g NaCl,
0.907g NaHCO3, 0.163g MgCl2∙6H2O, 1.47g CaCl2∙2H2O, 0.114g Na2SO4, and 0.545g
K2HPO4. The ionic concentration of each constituent of the SBF solution is shown in
Table 2.1. As can be seen, the solution represents a somewhat of a departure from
biological concentrations. This allows the coating process to be altered to facilitate
desirable coating formation while still utilizing the biomimetic process. To allow
sufficient time for dissolution, three minutes were elapsed for stirring prior to adding the
next chemical. This solution can be stored in a tightly capped bottle at room temperature
for several weeks without precipitation.
Immediately prior to coating, PEEK substrates were removed from the 10 M
NaOH solution and rinsed gently with DI water using a pipette. These were submerged
into 100 mL of SBF solution contained in a glass bottle. A piece of inert alumina ceramic
was placed over the opening of this bottle. This covered most of the area of the opening,
leaving a small portion of the opening exposed, which prevented pressure buildup within
the bottle while at the same time minimizing loss of heat and coating solution during
boiling. These were placed near the center of the 1200 W microwave oven and irradiated
26
Table 2.1: Ion concentrations of constituents of PEEK coating solution compared to
those of human blood plasma. [66]
Concentration (mM)
Ion
Human Blood Plasma
PEEK Coating Solution
Na+
142.0
490.9
Cl-
103.0
515.3
HCO3-
27.0
10.8
K+
5.0
21.5
Mg2+
1.5
0.8
Ca2+
2.5
10.0
HPO42-
1.0
3.1
SO42-
0.5
0.8
at full power for four minutes. Following this, the configuration was allowed to cool in
the microwave for one minute, before transferring the samples to another glass bottle
containing 100 mL of SBF solution. In this way, the samples were subjected to another
microwave coating procedure. This was done to ensure uniform coverage of the substrate
surface, as only surfaces exposed to the solution can nucleate the ACP precursors
necessary for coating formation. Following this second coating treatment, the PEEK
samples were gently rinsed with DI water and allowed to dry overnight in a furnace at
60°C.
27
2.2.3 Characterization
Hydrophilicity was assessed before and after coating of PEEK using a water
contact angle meter (Model CAM-MTCRO, Tantec), and subjected to a one-way
ANOVA analysis (n=4). Samples were examined using X-ray diffraction (XRD, Ultima
III, Rigaku) using monochromated Cu Kα radiation operated at a 40 kV voltage and 44
mA current. This was performed in parallel beam mode, due to the very thin SBF coating.
Visual features were investigated using scanning electron microscopy (SEM, S4800,
Hitachi) micrographs. Because moderate conductivity of samples is required for
successful use of SEM, the PEEK surface was further altered for visual clarity to this end.
This was achieved using a gold sputter coating (Cressington Sputter Coater 108 Auto) for
a duration of 30 seconds. With this treatment, samples were made sufficiently conductive
for successful SEM characterization. Elemental composition of the coatings was made
possible using the energy dispersive spectroscopy (EDS) attachment of the SEM. These
methods allowed a comprehensive examination of the coating formed by microwave
assisted biomimetic methods.
2.3
Results and Discussion
After both the etching and coating processes, the appearance of PEEK substrates
to the naked eye remains unchanged, as seen in Figure 2-1. This could potentially cause
problems if, before implantation, healthcare professionals wished to confirm the presence
of a coating. However, this problem can be quickly and inexpensively solved when
considering the extreme difference in hydrophilicity of coated and uncoated PEEK.
28
Figure 2-1: Visual comparison of uncoated (left), MW etched (center), and MW coated
(right) PEEK substrates.
Hydrophilicity is easily indicated by the water contact angle, with a lower angle
corresponding to a more hydrophilic surface. Water contact angle results can be seen in
Figure 2-2. Uncoated PEEK was found to have a water contact angle of 81 ± 4.1°, the
highest observed by a large margin. To illustrate the efficacy of the MW etching process,
the water contact angle was found to be 51.5 ± 4.4° for etched PEEK. After a microwave
assisted biomimetic coating procedure, this contact angle was drastically reduced to 8.7 ±
4.2°. Thus, hydrophilicity was found be very significantly affected by etching and coating
processes (p < 0.001).
It should be noted that while testing the coated sample, the water droplet
deposited on the surface spread over the entire top surface of the PEEK. This implies
that, given a larger surface area, an even lower contact angle would be observed, and
therefore even higher hydrophilicity is likely present in the coating. However, the
configuration of the water contact angle meter does not allow for a larger top surface, so
such a test cannot be done. However, the results obtained for coated PEEK can still be
29
100
Contact Angle (Degrees)
90
PEEK Water Contact Angle
80
70
60
Uncoated
50
MW Etched
40
MW Coated
30
20
10
0
Treatment Type
Figure 2-2: Water contact angle measurements conducted for PEEK with no prior
treatment (Uncoated), microwave assisted etching (MW Etched), and microwave assisted
biomimetic coating (MW Coated).
used as an upper bound for the contact angle, and as this angle is quite low, great
hydrophilicity is assured.
The very large difference in hydrophilicity between coated and uncoated PEEK
can easily solve the problem presented by the visual similarity of the two. If
confirmation, perhaps by a healthcare professional, of the presence of a coating is
desired, a micropipette can be used. After dropping an amount of water which is small
relative to the local surface of the implant, the droplet will form a tight bead on uncoated
PEEK, and spread out significantly on coated PEEK. The visual difference is instantly
recognizable, as seen in Figure 2-3. This provides an inexpensive and simple way to
reliably determine whether a particular implant is coated, though the two appear visually
identical. The patterns obtained from XRD analysis can be seen in Figure 2-4. As a
30
Figure 2-3: Visual illustration of differing hydrophilicity of uncoated (left), MW etched
(center), and MW coated (right) PEEK substrates.
semicrystalline polymer, the PEEK substrates incorporate an XRD signature that consists
of various peaks, labeled in Figure 2-4, as well as a broad region [89]. Both patterns
conform well to those expected for semicrystalline PEEK. However, as can be seen from
their identical shape, there is no evidence of a coating when examining XRD. This
suggests that the formed coating is amorphous. This confirms the previously mentioned
Figure 2-4: XRD patterns obtained for uncoated and coated PEEK.
31
Figure 2-5: SEM images at low magnification for uncoated (a) and coated (b) PEEK
substrates.
ACP formation mechanism, which predicts that a thin and amorphous coating will be
formed in the microwave environment. Thus, XRD analysis confirms the presence of an
amorphous coating devoid of any larger crystal structure.
Surface characteristics of both uncoated and coated PEEK samples at low
magnification can be seen in the SEM micrographs featured in Figure 2-5. The uncoated
surface is for the most part smooth and featureless, in sharp contrast to the coated surface,
where uniform coverage is seen to have occurred with no cracks present. In addition to
the base coating, several spherical Ca-P globules are seen to be present. These were likely
nucleated in solution and attached to the sample surface during the coating formation
process. Higher magnification images can be seen in Figure 2-6, along with the EDS
spectrum of the coating. The Ca/P ratio was determined to be 1.48, which is lower than
the stoichiometric hydroxyapatite Ca/P value of 1.67 [90]. This is most likely due to the
incorporation of substitutions in the HA structure by other ions, for example, CO32-. The
coating is seen to consist of many small Ca-P crystals which are needlelike in
32
Figure 2-6: High magnification SEM image (a) and EDS spectrum (b) of PEEK coating.
appearance. Additionally, the porosity is seen to be quite high. This small crystal size in
such a thin coating supports the amorphous determination made by XRD analysis.
2.4
Conclusion
To enhance the bioactivity of PEEK for application in biomedical implants, the
microwave coating process investigated offers several advantages. Contrary to all nonbiomimetic approaches, the resulting coating is bonelike, containing ionic substitutions
found in natural bone. This was confirmed by the relatively low Ca/P ratio seen in EDS
spectroscopy. Additionally, microwave coating takes places on very short time scales,
making it perfectly suitable for industrial application. The process is ideal for PEEK and
many other polymers because it takes place at the relatively low temperature of 100°C.
The results are promising and show great potential for the future of biomedical implants.
33
Chapter 3
Nitinol
3.1
Introduction
By coating the surface of an implant with a calcium phosphate (Ca-P) material,
surface bioactivity can be enhanced without sacrificing advantageous bulk properties of
the implant. The microwave assisted biomimetic methodology employed for polyether
ether ketone (PEEK) substrates described in Chapter 2 offers many advantages over
comparable approaches, including but not limited to fast coating time, bonelike
hydroxyapatite (HA), low temperatures, and low cost. The favorable results obtained for
titanium (Ti6Al4V) and PEEK with this approach provide justification for the
investigation of the method applied to new substrate materials [76]. One such material
that has recently garnered attention is nitinol, an intermetallic consisting of nickel and
titanium.
Nitinol is a promising candidate for use in orthopedic implants, due to its unique
shape memory properties. As a shape memory alloy, nitinol is able to recover to a
previously defined shape when heated above a specific temperature [91]. This property is
caused by a transition from the martensite phase present at low temperatures to the higher
34
temperature austenite phase [92]. In this manner, even fairly high strains of up to 6-8%
can be recovered. Application of this property allows nitinol to be used for biomedical
applications, such as bone clamps and sutures [93, 94]. When the devices have been
heated above the activation temperature, they exert a pressure on the clamped bone as
they begin to return to their previous shape. This heat activation can be achieved through
several means, including warm water, ambient body temperature, or an electric pulse [91,
93, 94]. The activation temperatures vary from roughly 30-60°C, and are able to fully
activate the nitinol component without undue irritation to the surrounding body tissue.
While nitinol is a unique material that may simplify and improve many medical
procedures, there are concerns regarding its usage. In a similar manner to PEEK, the
nitinol surface is not bioactive, and thus failure at the bone-implant interface is a
possibility. In addition to this, the nickel ion Ni3+ is known to be toxic, and its release
from the implant may cause health problems [95]. To prevent this, a coating procedure
that is able to deplete the surface of Ni3+ ions and also support a Ca-P outer layer is
necessary. This is easily obtainable by modestly adjusting the existing procedure used for
PEEK substrates in Chapter 2. Immersion in HNO3 prior to NaOH etching depletes the
surface of Ni3+ ions while also forming a TiO2 layer which will act against further
corrosion [96]. This is made possible due to the passivation of Ti in HNO3 alongside the
lack of passivation and subsequent release of Ni into the solution. By following this with
the standard procedures already implemented for PEEK, it is possible to create a nitinol
surface with both high bioactivity and low toxicity.
The elastic modulus of nitinol, which is greater than that of bone by more than a
factor of ten, takes on proportionally more of the load than the surrounding bone [85, 97].
35
This phenomenon, known as stress shielding, may pose problems for implants
constructed from solid nitinol in load-bearing applications. Underuse of bone causes a
decrease in the bone density, which can potentially lead to injury. Stress shielding is also
a problem for traditional titanium implants, and the situation has been remedied through
the construction of porous titanium implants [98, 99]. The increased porosity
compensates for the higher elastic modulus and can be used to construct an implant with
the desired stiffness. In addition, the higher surface area present in porous implants
provides more potential sites for bone attachment and a stronger bond at the interface.
For these reasons, a porous nitinol surface is a highly promising candidate for study.
3.2
Experimental Procedure
3.2.1 Material Preparation
Nitinol substrates were produced using metal 3-D printing techniques, and were
made to have a porous structure, in a grid-like pattern. The samples were cleaned in
acetone, 70% ethanol, and deionized water for 10 minutes each in an ultrasonic cleaner.
This was followed by air-drying overnight. All chemicals used were purchased from
Fisher Scientific.
To create the functional groups needed for biomimetic deposition, as well as to
limit the release of toxic Ni3+ ions into the surrounding tissues, it is necessary to perform
an alkali pre-treatment on the nitinol surface. The procedure followed by Liu et al.
incorporated a pre-treatment consisting of HNO3 followed by NaOH [96]. A similar
procedure was followed in this study, using 32.5% HNO3 to etch the surface at 60°C for
24 hours, followed by immersion in a 10 M NaOH solution at 60°C for 24 hours. For
36
each alkali treatment, specimens were submerged in the solution in a tightly capped bottle
within a furnace set to the defined temperature. Specimens were thoroughly rinsed with
deionized water between and after the treatments, and allowed to air dry overnight.
3.2.2 Microwave Assisted Coating
The coating procedure for the nitinol substrates is quite similar to the procedure
used for PEEK. However, slight modifications were made to the coating solution in the
interest of improving both coating formation and the simplicity of preparation. Due to
this, the solution departs somewhat from strict biological conditions, but contains the ions
necessary for the implementation of the biomimetic process. The solution was prepared
by dissolving the following chemicals, respectively, into 200 mL of water: 0.6612 g
Ca(NO3)2∙4H2O, 0.2016 g NaH2PO4, and 0.0672 g NaHCO3. Chemicals were stirred for
three minutes to ensure complete dissolution of each chemical before adding the next.
The ionic concentration of each constituent in the coating solution can be seen in
Table 3.1. This simpler composition eliminates chemicals not likely to be essential to the
biomimetic formation of calcium phosphate coating. Note that the HCO3- ion is still
present to allow the bonelike “carbonated” apatite to form.
To begin the coating process, the samples were submerged 100 mL of the coating
solution in an open glass bottle. The opening was partially covered with a piece of
alumina ceramic, which trapped most of the heat inside the bottle without generating
dangerously high pressures during boiling of the solution. The bottle was placed near the
center of the 1200 W microwave oven (Panasonic), and irradiated for four minutes at full
power. After allowing the setup one minute to cool, the samples were transferred to
another glass bottle along with the remaining 100 mL of coating solution. The samples
37
Table 3.1: Ion concentrations of constituents of nitinol coating solution compared to
those of human blood plasma [66].
Concentration (mM)
Ion
Human Blood Plasma
Nitinol Coating Solution
Na+
142.0
0
Cl-
103.0
0
HCO3-
27.0
4
K+
5.0
0
Mg2+
1.5
0
Ca2+
2.5
14.0
HPO42-
1.0
0
SO42-
0.5
0
NO3-
0
28.0
H2PO4-
0
8.4
were again coated in the microwave in the same manner. Because only surfaces that are
openly exposed to solution are able to form the Ca-P coating, performing two repetitions
ensures greater coverage. When completed, samples were gently washed with deionized
water and allowed to dry in a 60°C furnace overnight.
3.2.3 Characterization
Certain methods of characterization for the nitinol samples proved problematic
due to their porous structure. The presence of such large voids in the surface, while
38
beneficial for bone attachment, limit the amount of flat surface area for certain tests.
Water contact angle measurements cannot be performed with the equipment available, as
even the smallest water droplet produced by the test machine is too large for the available
surface area. Because of this, the water droplet will simply fall through the voids in the
structure. Similarly, this irregular surface, coupled with the fact that the coating is quite
thin, prevents the use of X-ray diffraction. However, scanning electron microscopy
(SEM) and energy dispersive spectroscopy (EDS) can be effectively used. To this end,
the samples were examined using SEM (S4800, Hitachi), and its EDS attachment using
an acceleration voltage of 10 keV. Because the base material is a conductive nickeltitanium alloy, gold coating was not necessary for the nitinol samples.
3.3
Results and Discussion
Unlike PEEK, the visual appearance of nitinol undergoes a noticeable change
after each step of the coating procedure. Figure 3-1 illustrates the unique appearances that
are present in uncoated, etched and coated forms, respectively. Uncoated nitinol is seen to
have a lustrous, reflective surface, which becomes much darker and loses its reflectivity
after etching. Subsequent microwave coating then alters the surface color to a lighter of
the surface after coating is due to the Ca-P coating, which has a white color. In this way,
a method still exists to accurately and instantly determine whether certain coating
procedures have been implemented successfully, despite porous implants not allowing for
the use of water contact angle measurements, as discussed above.
The surface features present for both coated and uncoated nitinol samples were
investigated using SEM. At very low magnification, the porous macrostructure can be
39
Figure 3-1: Visual comparison of uncoated (left), MW etched (center), and MW coated
(right) nitinol substrates.
seen to contain large voids before and after coating. This is shown in Figure 3-2. It is
easily seen that for the coated sample, a large amount of Ca-P structure has begun to
partially fill the voids. This partial filling provides a large surface area for bone
attachment without compromising the benefits of the porous structure.
At higher magnification, the surface features become more distinct. Both coated
and uncoated surfaces can be seen in Figure 3-3 under high magnification. The uncoated
Figure 3-2: SEM images of uncoated (a) and coated (b) porous nitinol structure at low
magnification.
40
Figure 3-3: SEM images of uncoated (a) and coated (b) nitinol surface at high
magnification.
surface is composed of many spheres of material, formed from the 3-D printing process
used to manufacture the samples. The coated image shows that the Ca-P coating
shade of grey. The change in color after etching is caused by titanium oxides being
formed that limit the ability of the surface to reflect light. The lighter colored appearance
has uniformly covered all exposed surfaces of the sample. The number of spherical
globules present, forming from amorphous Ca-P precipitation in solution and subsequent
attachment to the surface, is lower than for PEEK, but nonzero. This may be due to the
simpler coating solution used for the nitinol substrates. The coating itself exhibits a
needle-like morphology, as is expected from previous experimentation with PEEK and
titanium [76]. This structure is more easily observed in the higher magnification image
shown in Figure 3-4 (a). The very small crystal size present suggests that the coating is
most likely amorphous, as in the previous case of PEEK.
During SEM imaging, the EDS attachment was used to obtain an elemental
spectrum for the coating. This spectrum is shown in Figure 3-4 (b). Two points are
immediately obvious from this spectrum. First, the presence of calcium and phosphorous
41
Figure 3-4: SEM image of needle-like Ca-P coating structure (a) and associated EDS
spectrum (b).
indicates that the coating is present, and the associated Ca/P ratio of 1.64 indicates that
the structure is similar to hydroxyapatite (Ca/P ratio of 1.67) but slightly lower [90]. This
decreased Ca/P ratio is explained by the presence of CO32- substituting in the
hydroxyapatite structure, hence the “bonelike” description applied to biomimetic
coatings. Second, nickel does not appear in the spectrum. This absence is caused by both
the extraction of Ni3+ ions during the pretreatment and subsequent covering by the Ca-P
coating. In any case, the EDS data supports the determination that a coating suitable for
bone attachment is present on the surface, and that there exists a low concentration of
toxic Ni3+ ions in this coating.
3.4
Conclusion
Nitinol provides a very promising material for future use in biomedical implants.
It has a number of potential applications, due to its shape memory alloy behavior.
Additionally, the material may be manufactured to introduce sufficient porosity into its
structure so as to tune the stiffness to be most similar to human bone. These factors
provide motivation to investigate the feasibility of coating nitinol with bioactive Ca-P
42
materials. This study applied novel microwave assisted techniques to this end, and found
that with minor changes to previous procedures, such a coating can indeed be
successfully produced. While the porous morphology prevents certain characterization
methods from being used, the SEM and EDS analysis confirmed that a coating similar to
those previously obtained was attached to the material surface, and that toxic Ni3+ ions
were sufficiently drained from the surface, as planned. These results show that there is
great promise for further study of bioactive Ca-P coatings on nitinol.
43
Chapter 4
Conclusion
The goal of this study was to investigate the feasibility of coating the biomedical
implant materials polyether ether ketone (PEEK) and nitinol with a novel microwaveassisted biomimetic approach. This approach was first successfully applied to Ti6Al4V
substrates by our research group, and the advantageous properties of PEEK and nitinol
provide suitable motivation for the extension of the approach to new materials [76].
PEEK is a polymer whose elastic modulus can be altered during fabrication. By adjusting
this modulus to match that of human bone, stress shielding can be eliminated [86]. This,
along with its extreme inertness, makes PEEK a promising orthopedic candidate. Nitinol
is a nickel-titanium intermetallic which exhibits shape memory properties. This allows it
to reverse certain deformations and be used to fixate tissues as a clamp or suture [92-94].
Though its elastic modulus is much higher than bone, introducing a porous structure can
adjust the stiffness to approximate that of bone, and reduce stress shielding.
Neither PEEK nor nitinol are bioactive without a surface treatment, and thus
require a surface modification prior to application. A calcium phosphate (Ca-P) coating
enhances bioactivity, allowing bone to bond directly to the implant surface. In the case of
nitinol, this process can remove toxic Ni3+ ions near the surface before they come into
44
contact with the body. The biomimetic approach can provide high quality thick coatings
that mimic actual bone chemistry, but are unfortunately quite time consuming, on the
order of days or weeks. By introducing microwave irradiation to the biomimetic
methodology, coating time is drastically reduced to minutes. This allows coating of
PEEK and nitinol in a manner efficient enough to be applied in industry.
Coatings obtained in this way were examined using scanning electron microscopy
(SEM) and were seen to provide complete coverage of the implant, even in the case of
porous nitinol. The calcium to phosphate ratio was found using energy dispersive
spectroscopy (EDS) to be consistent with values expected for bonelike Ca-P, which
contains substitutions of other ions, such as CO32-. This coating visually appeared to be
amorphous, and in the case of PEEK, this was confirmed through X-ray diffraction
(XRD). To ensure the presence of a coating, visual examination of the water contact
angle and surface coloring proved sufficient for PEEK and nitinol, respectively.
The coatings obtained using this microwave-assisted biomimetic technique were
found to be of suitable quality to warrant further investigation. Because the process is
simple and fast, this microwave-assisted process is well-suited to industrial applications.
For this to happen, the behavior of the coatings in animal and eventually human studies
must be investigated. Future work should focus on these trials and in optimizing the
coatings for biomedical application.
45
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