Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02550457 2006-06-15
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BIOCERAMIC COATING OF A METAL-CONTAINING SUBSTRATE
Field of the Invention
The present invention is related to coating of a metal-containing substrate
with a bioceramic material.
Background of the Invention
Materials implanted in vivo essentially have direct contact with the human
body through the interface between the implant surface and bones, tissues and
extracellular body fluids. The surface of the implant therefore plays a very
important role related to surface chemistry, topography and micro/nano
structure,
and tribological properties. Major issues related to surface modification
processes
include corrosion and wear resistance of the implant and biocompatibility and
bioactivity. Chloride ion concentration in body fluid is 113 mEql-l and in
interstitial
fluid is 117 mEql-', which may corrode metallic materials. Body fluids contain
amino acids and proteins that tend to accelerate corrosion. Toxicity and
allergy
occur if metallic materials are corroded by fluid, if metallic ions are
released into the
fluid for a long time, or if ions combine with biomolecules such as proteins
and
enzymes. Loosening of implant could occur due to the wear of the implant. All
of
these factors lead to premature implant failures, debilitating pain, and
surgical
revisions.
Both corrosion and wear are related to the surface of implants. Extensive
studies have been reported on surface modifications to understand and enhance
the performance of implants. One approach is to modify the surface topography
by
creating a rough or porous surface on the implant to increase the surface area
available for bone/implant apposition, which improves the fixation of the
implant in
the bone. A natural consequence of increasing the surface area is an increase
in
metal ion release, due to an increased surface contact with corrosive media. A
further complication is the increase in wear debris due to increased surface
friction,
which also results in increased ion release rates and loosening of the
implants.
Another approach to surface modification is to coat the implant surface with
hard
materials focusing on increasing the wear resistance. Titanium nitride was
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extensively reported for implant surface modification using chemical vapor
deposition (CVD) and physical vapor deposition (PVD). Although these methods
provide the implant articulating surfaces with excellent wear resistance, the
deposited layers often suffer from lack of adherence and are not associated
with
bone/implant apposition. Low energy nitrogen ion bombardment-plasma nitriding
is
one of the most up-to-date methods for improving the wear and corrosion
behavior
of metallic alloy. In plasma nitriding, a Ti-based substrate is directly
involved in the
reaction of coating formation, which results in an excellent adhesion of the
coating
to the substrate. However, the inherent high cost of plasma nitriding
equipment
and its operation reduces its cost-effectiveness.
Other surface coatings have been tried to improve the bone/implant interface
bonding. These include hydroxyapatite (HA) coatings produced by plasma spray
or
ion implantation. Hydroxyapatite, (Cajo(P04)6(OH)2), is characterized by a
hexagonal structure (a = 9.423 A, c = 6.875A, Space Group: P63m) with a
density
of 3.16 g/cm3. It is one of the three main components of the human body (HA,
water and collagen) and is able to integrate bone structure and support bone
ingrowth. For this reason, coatings of hydroxyapatite are often applied to
metallic
implants to alter the surface properties. In this manner the body sees the
hydroxyapatite-type material as a compatible material. Without the coating,
the
body would see a foreign body and either isolate it from surrounding tissues
or
induce a tissue reaction.
However, HA coatings formed by plasma spray, the most popular
commercially available technique for HA coating on implants, generated some
long
term concerns. A study has revealed that even though uncemented HA-coated hip
prostheses had better survivorship than cemented, the HA cups with follow-up
longer than 6 years revealed an increased surgical revision rate (replacement
of the
primary implant). Also in a study about polyethylene wear, osteolysis and
acetabular loosening with HA-coated prostheses, there were no stem revisions
but
24% of the acetabular components required revision. HA debris might accelerate
the wear of the high density polyethylene material (HDPE) of the acetabular
component. Another study of HA coating on a G.B. acetabular cup found a high
rate of debonding and failure. Yet another study reporting on the evaluation
of 6
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revisions of HA-coated acetabular cups showed HA granules embedded in the
HDPE, which may produce severe clinical problems.
There are a variety of known techniques to produce HA coatings on
substrate surfaces. Plasma spray advantageously produces high density
coatings,
but disadvantageously is a line-of-sight process and oxidation of powder when
conducted in air leads to poor adhesion and low purity coating. High velocity
oxyfuel advantageously provides good coating bond strength, but
disadvantageously is a line-of-sight process and produces low purity coatings.
Ion
bean assisted deposition advantageously uses low deposition temperature,
provides high adhesion and provides good control of stress level,
microstructure
and composition, but disadvantageously is a line-of-sight process and is
higher in
cost. Pulsed laser deposition advantageously provides high purity coatings,
but
disadvantageously is a line-of-sight process, requires high capital investment
and
maintenance costs and provides a low deposition rate. Chemical vapor
deposition
advantageously is not line-of-sight dependent, readily provides coatings at
near
theoretical density and permits control of preferred grain orientation and
grain size,
but disadvantageously is a high temperature process in most cases leading to
low
purity HA coatings. Electrodeposition is advantageously low cost and simple
and
provides uniform coatings of high purity and low porosity, but
disadvantageously is
a line-of-sight process to some extent and is a two-step process that must be
followed by hydrothermal treatment to obtain HA coatings. Electrophoresis
deposition advantageously is not a line-of-sight process, is low cost and
simple,
provides high deposition rate and produces a wide range of coating thicknesses
(from < I um to >500um), but disadvantageously is a two-step process requiring
densification by sintering which may reduce the purity of the HA coating. Sol-
gel
deposition advantageously permits coating of complex shapes with coatings
having
increased homogeneity and fine-grained structures, but disadvantageously
requires
firing leading to reduced purity of the HA coating. Bio-mimetic deposition
advantageously is a low temperature process applicable to any heat sensitive
surface including polymers, permits formation of bone-like apatite crystals
with high
bioactivity and permits incorporation of bone growth stimulating factors and
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antibiotics, but disadvantageously is a very slow process requiring precise
control
of process parameters in which obtaining uniform coating is a practical
challenge.
Finally, chemical deposition is a process mainly used to prepare HA powders
but not to coat HA on a substrate. Few studies of chemical deposition of
bioceramic materials are available and process kinetics are poorly understood.
In
theory, chemical deposition may be able to provide uniform coatings of
unlimited
thickness on complex shapes, be used to deposit HA on polymer surfaces, and
produce a porous top layer to encourage bone ingrowth. No suitable chemical
processes are commercially available for coating.
Of the processes described above, most are line-of-sight dependent and/or
involve high temperature (over 15,O00 C for plasma spray). It is a challenge
for
any process that is line-of-sight in nature to produce uniform coating,
particularly on
sloped and curved surfaces. As for processes that rely on high temperature,
they
cause decomposition of HA which leads to the formation of impurities such as
tetracalcium phosphate (Ca4P2O9), amorphous calcium phosphate, a-tricalcium
phosphate (Ca3(PO4)2), and P-tricalcium phosphate (Ca3(PO4)2). These
impurities
are unstable in the body fluids and cause serious concerns for localized
corrosion.
The selective dissolution of these impurities may result in an accelerated
wear
caused by the roughening/scoring of the articulating surface, and this debris
will, in
turn, make the wear a more severe issue.
It is apparent from the processes described above that biomimetic and
chemical processes are neither line-of-sight dependant nor involve high
temperature operation. Biomimetic coating is an approach that consists of
immersion of metal implants in simulated body fluids (SBF) at a physiologic
temperature and pH. HA coating, the major component of bone, grows in a way
similar to the natural bone growth in our body. This process produces HA
coating
with desirable properties such as high purity and bioactivity. Another
uniqueness of
this process is its capability to incorporate antibiotics (e.g. tobramycin),
proteins and
bone growth stimulators (e.g. osteogenics). However, although SBF mimics the
inorganic composition, pH, and temperature of human blood plasma, achieving a
reasonable coating thickness for practical applications takes a long time.
Long
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immersion time (7-14 days) with daily refreshment of SBF's is required. The
difficulty results from the metastability of SBF and the process requires
replenishment and a constant pH to maintain supersaturation for apatite
crystal
growth. As a result of the low solubility product of HA and the limited
concentration
range for the metastable phase, this operation is extremely difficult and
might lead
to local precipitation or uneven coatings. Such an intricate and long process
can
hardly be tolerated in the prostheses coating industry.
Chemical coating processes produce HA coatings at low temperature and
are line-of-sight independent. Theoretically, chemical processes can produce
uniform coatings of unlimited thickness on complex shapes. The deposition rate
of
chemical HA coating is significantly higher than the biomimetic process due to
significantly higher and controllable process parameters. Unfortunately,
little is
known about its chemical reaction kinetics and the process is used mainly for
producing HA powder.
There remains a need in the art for a chemical process for coating a
bioceramic material, e.g. hydroxyapatite (HA), on a surface of a substrate.
Summary of the Invention
There is provided a process for coating a surface of a metal-containing
substrate with a bioceramic material, comprising: activating the surface of
the
metal-containing substrate by applying a voltage to the substrate in a liquid
containing an electrolyte; and, immersing the substrate in a deposition
solution
containing the bioceramic material or precursors for the bioceramic material
to form
a coated substrate.
There is further provided a process for coating a surface of a metal-
containing substrate with a bioceramic material, comprising: activating the
surface
of the metal-containing substrate by applying a voltage to the substrate in a
liquid
containing an electrolyte; immersing the substrate in a deposition solution
containing the bioceramic material or precursors for the bioceramic material
to form
a coated substrate; and heat treating the coated substrate.
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There is yet further provided a metal-containing substrate coated with a
bioceramic material.
There is still yet further provided a prosthesis comprising a metal-containing
substrate coated with a bioceramic material.
In comparison to prior art processes, e.g. plasma spray processes,
processes of the present invention advantageously permit the formation of
purer
bioceramic coatings which contain fewer impurities leading to fewer
imperfections
or holes in the coating leading to more durable coatings. Further, uniform
coatings
on complex geometries may be achieved with relative ease. Also, smaller
particle
sizes in the coating may be obtained. Furthermore, the present processes are
simpler and less expensive than prior art processes. The present processes may
be conducted at lower temperatures; they are not line-of-sight dependent; they
have excellent scalability; and they incur low capital investment and lower
maintenance and operation cost.
Activation of the substrate:
The present processes involve activating the surface of a metal-containing
substrate by applying a voltage to the substrate in a liquid containing an
electrolyte.
Electrochemical activation of the surface sensitizes the surface to deposition
of the
bioceramic material during the coating process.
Voltage may be applied to the substrate by DC current. Applied voltage may
result in polarization of the surface of the substrate. Preferably the
substrate is
used as an anode and the voltage is applied anodically. If desired, an AC
perturbation may be superimposed over the applied voltage. The applied voltage
(or applied average voltage in the case of an applied voltage with an AC
perturbation) is preferably in a range of from about 1 V to about 25 V,
preferably
from about 1 V to about 20 V, more preferably from about 2 V to about 20 V,
even
more preferably from about 7.5 V to about 12.5 V. Application of too high a
voltage
during activation may ultimately result in poor coating performance.
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Voltage may be applied for any time duration that suitably activates the
surface, preferably not less than about 1 minute. More preferably, the
duration over
which voltage is applied is about 30 minutes or more. Current density is
preferably
in a range of from about 0.05 A/cm2 to about 0.2 A/cm2, more preferably from
about
0.08 A/cm2 to about 0.18 A/cm2, even more preferably from about 0.1 A/cm2 to
about 0.15 A/cm2.
Magnitude of applied voltage, time duration and current density during
activation of the substrate surface may ultimately affect coating thickness.
Activation may be conducted at any convenient temperature provided the liquid
containing the electrolyte remains in a substantially liquid state.
Activation of the surface of the substrate is performed in a liquid-based
system, for example a solution of an electrolyte or a molten electrolyte.
Solution-
based systems are preferred. Solution-based systems have a solvent, for
example
water, ammonia, etc., and an electrolyte. The electrolyte is chosen to provide
a
negative charge to the surface of the substrate. For example, the electrolyte
may
be a basic electrolyte that generates anions in the solvent, the anions
providing a
negative charge on the surface of the substrate. The solvent system is
preferably
water. The electrolyte is preferable a base or mixture of bases, for example
alkali
metal hydroxides, alkaline earth metal hydroxides or mixtures thereof. Some
suitable electrolytes are sodium hydroxide, potassium hydroxide, lithium
hydroxide,
calcium hydroxide or mixtures thereof. Sodium hydroxide, potassium hydroxide
or
mixtures thereof are particularly preferred.
In solution-based systems, the electrolyte may be present in any suitable
concentration that results in activation of the surface of the substrate.
Preferably,
the concentration is in a range of from about 0.1 M to about 20 M, more
preferably
from about 5 M to about 15 M.
In one embodiment of the invention, activation of the substrate surface may
be performed with DC current having a current density of about 0.1 A/cm2 at an
applied voltage of about 10 V for about 30 minutes in a 10 M aqueous solution
of
sodium hydroxide.
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Activation may also include sonication. Sonication during activation, for
example with ultrasound, may enhance the coating process when coating is
performed over longer periods of time (e.g. 24 hours or more).
The metal-containing substrate is any material comprising a metal which can
be activated as previously described and on to which a bioceramic material can
be
coated. The metal-containing material may be, for example, a pure metal, an
alloy
or a metal-containing composite. Metal-containing composites may be, for
example, metal-containing ceramics, or composites of one or metals and a
polymer.
Examples of some metals that may be present in the metal-containing
substrate are Ti, Zr, Cr, Co, Au, Pt, Ag, Ni, Cu, Mg, Ca, and stainless steel.
Metal-
containing substrates containing a Group 4B metal are of particular note. In
one
embodiment, the metal-containing substrate contains Ti, Zr or mixtures
thereof. Ti-
containing materials are preferred, for example Ti alloys or Ti-containing
composites (e.g. Ti-HDPE composite). A particularly preferred substrate is
Ti6AI4V
alloy.
Coating of the substrate:
In order to coat the substrate to form a coated substrate, the activated
substrate is immersed in a deposition solution containing bioceramic material
or
precursors for the bioceramic material. Precursors are chemical entities which
when combined, for example through chemical reaction, form the bioceramic
material. The bioceramic material forms on to the surface of the substrate
forming
a coating.
The bioceramic material deposited on the surface of the substrate is
preferably hydroxyapatite (HA). Preferably, the deposition solution contains
precursors for HA, for example calcium ions and orthophosphate ions. Calcium
ions and orthophosphate ions may be accompanied by counter ions. The
deposition solution may contain other components, for example other salts
(e.g.
sodium, potassium and/or magnesium salts having counter-anions, for example
chloride, bicarbonate and/or sulfate).
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The deposition solution comprises a solvent and either bioceramic material,
precursors for the bioceramic material or a mixture thereof dissolved therein.
For
HA coating, the solvent is preferably water. HA has a tendency to precipitate
from
aqueous solution, particularly at high pH. It is desirable to deactivate the
deposition
solution by reducing the pH of the solution to enhance selective formation of
HA
coating on the substrate. At the same time, it is preferable to have a
saturated
solution of HA or HA precursors to increase deposition rate of the HA on to
the
substrate. Preferably, the pH is less than about 8, more preferably in a range
of
from about 6 to about 8. If the pH of the deposition solution is too low, the
solution
may act to deactivate the surface of the substrate leading to poorer coating
performance.
The pH of the deposition solution may be lowered with pH adjusting agents,
for example acids (e.g. hydrochloric acid, phosphoric acid, etc.) to reduce
unwanted
precipitation of HA. In one embodiment buffers containing HCI or TRIS (tris-
hydroxymethyl aminomethan) are used to adjust the pH.
During deposition it is desirable, although not necessary, to replenish the
deposition solution with more HA or HA precursors in order to maintain a
saturated
solution of HA or HA precursors to keep the HA deposition rate substantially
constant. Replenishment of the deposition solution may be conducted at any
suitable time. Preferably, replenishment occurs at regular intervals, for
example
every 5 to 60 minutes. Replenishment increases coating growth on the
substrate,
and more frequent replenishments lead to more coating.
Activation of the substrate surface together with deactivation of the
deposition solution leads to coating of the substrate surface rather than
precipitation of HA in the solution. Further, by selectively activating a part
of the
substrate, it is possible to selectively coat that part. Surprisingly, the
coating
process appears to be "autocatalytic" in that the initial covering of the
surface of the
substrate does not inhibit further coating.
Additional materials may be incorporated into the coating. Such
incorporation may be achieved by including one or more of the additional
materials
in the deposition solution. Inclusion of the one or more additional materials
may be
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effected at any time during the coating process. For example, additional
material
may be included in the solution throughout the coating process, only at the
beginning of the coating process, only at the end of the coating process, in
the
middle of the coating process, or at staggered intervals during the coating
process.
For medical applications, additional materials may be, for example, bone
growth
stimulating factors, antibiotics, proteins, hormones, etc.
The substrate may be immersed in the deposition solution for any suitable
length of time to form a coating on the substrate surface. Longer immersion
times
lead to thicker coatings. The substrate may be immersed in the deposition
solution
for a duration of 0.5 hours or more. Durations of 10 hours or more, preferably
15
hours or more lead to coating thicknesses acceptable for medical applications.
Coating thicknesses of up to 50 pm or more can be achieved.
Coatings produced by the present process have excellent morphological
characteristics. For example, average grain size is smaller than in coatings
produced by prior art processes. By the process of the present invention it is
possible for the coating to have an average grain size in the nano-scale, for
example less than 20 nm in size, particularly in a range of about 10-20 nm in
size.
Further, nanoporous structures can be formed having pore diameters less than
800
nm, for example 200-500 nm. Such pore sizes are favourable for encouraging
bone growth into the surface of a coated implant.
One of the problems with prior art processes is that HA decomposes,
particularly at high temperatures, to form other calcium phosphate compounds
which contaminate the coating. Such contaminants lead to imperfections or
holes
in the coating leading to a decrease in durability. The present process
permits
deposition of very pure HA coatings with significantly reduced levels of
contaminants since HA is selectively deposited on the substrate under gentle
conditions, leading to more durable coatings.
Heat treatment of the coated substrate:
After coating the substrate with the bioceramic material, it may be desirable
to heat treat the coated substrate to increase bond strength of the coating on
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substrate. Heat treatment is preferably performed at a temperature below the
temperature at which HA begins to decompose, which is about 800 C. More
preferably, the heat treatment temperature is in a range of from about 350 C
to
about 800 C, for example from about 350 C to about 650 C, or from about 350 C
to
about 600 C, or from about 350 C to about 550 C, or from about 500 C to about
650 C, or from about 500 C to about 600 C, or from about 550 C to about 650 C.
In one embodiment, a temperature of about 550 C may be used. Heat treatment is
preferably conducted in a gaseous medium, for example air, argon, neon,
helium,
nitrogen or mixtures thereof. In situations where only part of a substrate is
to be
coated, it is sometimes desirable to conduct heat treatment in a gas that is
inert to
the substrate to reduce the possibility of damaging the substrate, for example
through oxidation. Heat treatment may be conducted for any suitable length of
time, for example for 0.5 hours or more, particularly for about 1-2 hours.
Heat
treatment can lead to an increase in coating bond strength of over four times.
Coating bond strengths of 24 MPa or more can be achieved.
Applications:
Processes of the present invention are useful for any application in which the
coating of a bioceramic material on a metal-containing substrate is desired.
The
processes are particularly useful in the fabrication of medical devices, e.g.
prostheses, especially prosthesis for replacing bone tissue. Prostheses
include, for
example, replacements for limbs (e.g. arms and legs), digits (e.g. fingers and
toes),
facial bones, hip bones, spinal bones, and parts thereof. Prostheses may be
fully
or partially implanted in a body of an animal, for example a human.
Further features of the invention will be described or will become apparent in
the course of the following detailed description.
Brief Description of the Drawings
In order that the invention may be more clearly understood, embodiments
thereof will now be described in detail by way of example, with reference to
the
accompanying drawings, in which:
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Fig. 1 is a graph of coating thickness (pm) as a function of NaOH
concentration (M);
Fig. 2 is a graph of coating thickness (pm) as a function of applied voltage
(volts);
Fig. 3 is a graph of coating thickness (pm) as a function of activation time
(minutes);
Fig. 4 is a graph of coating thickness (pm) as a function of DC current
density (A/cm2);
Fig. 5 is a graph of coating thickness (pm) as a function of activation
temperature ( C);
Fig. 6 is a graph of coating thickness (pm) as a function of time (hours)
illustrating effect of replenishing deposition solution on growth rate of an
HA
coating;
Fig. 7 is a graph of coating thickness (pm) as a function of time (hours)
comparing calculated and minimum observed coating thicknesses;
Fig. 8 is a scanning electron micrograph showing a cross-section of a coated
substrate with locations of EDX point analysis measurements thereon;
Fig. 9 is a scanning electron micrograph of an HA coating showing pore size;
Fig. 10a is a diffraction paftern from transmission electron microscopy (TEM)
analysis of an HA coating;
Fig. 10b is a transmission electron micrograph showing crystal planes inside
a grain of an HA coating;
Fig. 10c is a transmission electron micrograph showing grains of a single
plate of an HA coating; and,
Fig. 11 is a graph of coating adhesion strength (MPa) as a function of heat
treatment temperature ( C) for heat-treated HA-coated substrates.
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Description of Preferred Embodiments
Other advantages that are inherent to the structure are obvious to one skilled
in the art. The embodiments are described herein illustratively and are not
meant
to limit the scope of the invention as claimed. Variations of the foregoing
embodiments will be evident to a person of ordinary skill and are intended by
the
inventor to be encompassed by the following claims.
Preparation of Substrate:
A 10 mm x 10 mm x 1.7 mm plate of Ti6AI4V-ELI (extra-low interstitial) alloy
formed in accordance with ASTM standard F136-98 having a chemical composition
(wt%) of C 0.02, N 0.008, Fe 0.213, Al 6.16, V 3.92, 0 0.12 and Ti balance
(available from RMI Titanium Company, Mississauga, Canada), was mechanically
polished using SiC paper #400 and #600, and 9 pm A1203 paper. A titanium wire
was spot-welded to the plate for handling. The plate was ultrasonically
cleaned for
10 minutes in acetone, then 10 minutes in ethanol and then 10 minutes in
deionized water. The cleaned plate was then etched for 10 minutes in a dilute
HF
acid solution, rinsed in deionized water, ultrasonically cleaned in deionized
water
for 10 minutes and then dried with cold air.
Activation:
One Ti6AI4V alloy plate prepared as described above was used as the
working electrode in an electrochemical cell in the activation of the plate
surfaces.
Two other Ti6AI4V plates cleaned in ethanol were used as counter electrodes,
but
the plates of the counter electrode had surface areas that were at least twice
as
large as the surface areas of the plates of the working electrode. Activation
of plate
surfaces of the working electrode for each example was accomplished
electrochemically by application of a DC voltage to the plates immersed in an
aqueous solution of NaOH according to parameters listed in Table 1. In
experiments where the effect of ultrasound was investigated, ultrasound at a
frequency of 40 2 KHz was applied during activation. In experiments where the
effect of ultrasound was not under investigation, ultrasound was not used.
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Table 1
Ex. NaOH conc. Voltage Current density Time Temp ( C)
(M) (V) (A/cm2) (min)
Al 1 5 30 Ambient
A2 2 5 30 Ambient
A3 5 5 30 Ambient
A4 10 5 30 Ambient
A5 15 5 30 Ambient
A6 20 5 30 Ambient
A7 10 1 30 Ambient
A8 10 2 30 Ambient
A9 10 5 30 Ambient
A10 10 10 30 Ambient
All 10 12.5 30 Ambient
A12 10 15 30 Ambient
A13 10 17.5 30 Ambient
A14 10 20 30 Ambient
A15 5 10 1 Ambient
A16 10 10 1 Ambient
A17 5 10 10 Ambient
A18 10 10 10 Ambient
A19 5 10 30 Ambient
A20 10 10 30 Ambient
A21 5 10 60 Ambient
A22 10 10 60 Ambient
A23 5 10 120 Ambient
A24 10 10 120 Ambient
A25 10 4.5 0.01 30 Ambient
A26 10 4.9 0.02 30 Ambient
A27 10 4.8 0.03 30 Ambient
A28 10 6.7 0.04 30 Ambient
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A29 10 25 0.05 30 Ambient
A30 10 10 0.08 30 Ambient
A31 10 10 0.10 30 Ambient
A32 10 ? 0.15 30 Ambient
A33 10 25 0.2 30 Ambient
A34 10 10 30 25
A35 10 10 30 30
A36 10 10 30 40
A37 10 10 30 50
A38 10 10 30 60
Procedure for Coating:
Deposition solutions saturated with hydroxyapatite (HA) precursors were
prepared by dissolving sodium chloride (Fluka, ~99.5%), sodium bicarbonate
(Sigma-Aldrich, ~99.7%), potassium chloride (Fisher, ~99.6%), sodium
orthophosphate (Sigma-Aldrich, >99.0%) and magnesium chloride hexahydrate
(Sigma-Aldrich, >99.0%) in deionized water, followed by the addition of 1 M
hydrochloric acid to reduce the pH to about 6, then the addition of calcium
chloride
hexahydrate (Fisher, ~99.5%) and sodium sulfate (Anachemia, >99.0), and then
the
addition of 1 M TRIS (tris-hydroxymethyl aminomethan) to adjust the pH of the
solution to 6.5. Calcium chloride was added after acidification with
hydrochloric
acid to reduce the possibility of precipitating hydroxyapatite (HA).
Alternatively, the
calcium chloride could be added before acidification and the sodium
orthophosphate added after acidification.
The various reagents and deionized water were used in amounts to provide
a deposition solution with the following concentrations of ions:
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Na+ 142.0 mM
K+ 5.0 mM
Mg2+ 1.5 mM
Ca2+ 12.5 mM
CI- 159.0 mM
HC03- 4.2 mM
HP042- 5.0 mM
SO42- 0.5 mM
Concentrations of the ions in the deposition solution are generally similar to
concentrations found in blood plasma and simulated body fluid (SBF), although
the
concentration of calcium ions (Ca2+) and orthophosphate ions (HP042-) in the
deposition solution are five times their concentration in blood plasma and
SBF.
To coat a substrate, 175 ml of the deposition solution in a 250 ml beaker
were placed in a water bath at 37 C for 3 min to raise the temperature of the
deposition solution to 37 C. Activated Ti6AI4V alloy plates were weighed to
five
decimal places and immersed in the deposition solution by hanging them in the
solution for a desired length of time. After the desired length of time
elapsed,
coated Ti6AI4V alloy plates were air dried and weighed. The difference between
the weight of the coated and uncoated plates gave the weight of the coating
material.
Effect of NaOH Concentration in the Activating Solution:
Activated Ti6AI4V alloy plates prepared in accordance with Examples A1-A6
were coated with HA over 30 minutes in accordance with the procedure for
coating
described above. A graph of coating thickness (pm) as a function of NaOH
concentration (M) is provided in Fig. 1. Coating thickness is calculated from
weight
gain based on fully dense HA. Coating thickness is a maximum when the
concentration of NaOH during activation is about 10 M. The activating solution
was
very viscous when the concentration of NaOH was 20 M. Scanning electron
micrographs (SEM) of the coating surfaces revealed that they were all similar
in
morphologies and plate-like.
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Effect of Magnitude of Applied Voltage During Activation:
Activated Ti6AI4V alloy plates prepared in accordance with Examples A7-
A14 were coated with HA over 5 hours in accordance with the procedure for
coating
described above. A graph of coating thickness (pm) as a function of applied
voltage (volts) is provided in Fig. 2. Coating thickness is calculated from
weight
gain based on fully dense HA. Coating thickness is a maximum when the applied
voltage during activation is between 7.5 and 12.5 volts, for example around 10
volts. Voltages higher than 20 volts can cause severe reaction, resulting in
rounded edges and grooves on the substrate surface, likely due to dissolution
of
the substrate. SEM results show that coating morphology is affected by the
magnitude of the voltage applied during activation. Voltages of 10 volts or
less
resulted in fine needle-like coatings, while voltages in excess of 20 volts
resulted in
coarser coatings.
Effect of Duration of Applied Voltage During Activation:
Activated Ti6AI4V alloy plates prepared in accordance with Examples A15-
A24 were coated with HA over 5 hours in accordance with the procedure for
coating
described above. A graph of coating thickness (pm) as a function of activation
time
(minutes) is provided in Fig. 3. Coating thickness is calculated from weight
gain
based on fully dense HA. Coating thickness is a maximum when the activation
time
is generally 30 minutes or more.
Effect of Current Density During Activation:
Activated Ti6AI4V alloy plates prepared in accordance with Examples A25-
A33 were coated with HA over 5 hours in accordance with the procedure for
coating
described above. A graph of coating thickness (pm) as a function of DC current
density (A/cm2) is provided in Fig. 4. Coating thickness is calculated from
weight
gain based on fully dense HA. Coating thickness is a maximum when the current
density is around 0.1 A/cm2. Currently densities greater than about 0.2 A/cm2
can
lead to rounded edges and grooves on the surface. SEM confirms that the
coatings have plate-like structures at all current densities.
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Effect of Temperature During Activation:
Activated Ti6AI4V alloy plates prepared in accordance with Examples A34-
A38 were coated with HA over 5 hours in accordance with the procedure for
coating
described above. A graph of coating thickness (pm) as a function of activation
temperature ( C) is provided in Fig. 5. Coating thickness is calculated from
weight
gain based on fully dense HA. It is evident that activation temperature has
little
effect on coating thickness. SEM indicates that coatings all have needle-like
structures.
Effect of Replenishing HA Solutions During Coating:
The procedure for coating described above was carried out with
replenishment of the deposition solution every half hour with freshly made
solution.
The coated substrates were taken out of solution at time periods of 0.5, 1, 2,
3, 4
and 5 hours. A graph of coating thickness (pm) as a function of time (hours)
illustrating effect of replenishing the deposition solution at half hour
intervals on the
growth rate of the HA coating is provided in Fig. 6. Coating thickness is
calculated
from weight gain based on fully dense HA. It is evident that replenishing
solutions
significantly increases coating growth on the substrate.
Two similar experiments, one in which replenishment was not done and one
in which replenishment was done at 1 hour intervals confirmed that more
frequent
replenishing leads to a greater amount of coating on the substrate surface.
In the experiment where replenishment was done at half hour intervals, SEM
indicated that morphologies of coated Ti6AI4V substrates at different time
periods
have a bone-like structure, and to some extent a crystal-like structure,
covering the
whole surface of the substrate. After 3 hours, the coating grows to such a
thickness
that the coating starts to crack, likely due to either internal stress or
drying. The
morphology of the coating at a half hour indicates that HA coating initiates
from
some active areas and grows in a spherical shape extruding on the surface.
Gradually valleys around the spherical extrusions start to be covered by HA
coating
leading to a more uniform coating surface with time.
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HA coating after 5 hours of coating with replenishing solution every one hour
leads to more crystal-like coating morphologies, compared to the bone-like or
less
crystal-like morphologies indicated above. There are more cracks in the
coating
with less frequent replenishing.
Growth of HA Coatings:
A longer term coating process was performed in which HA was coated on a
Ti6AI4V substrate for 15 hours with replenishment of the deposition solution
every
half hour. A linear relationship between coating duration and coating
thickness was
observed. Within 15 hours the coating thickness reached about 50 pm, which is
an
acceptable thickness for hydroxyapatite coating in medical applications.
Observed
coating thickness was measured from an SEM of a cross-section of the coated
substrate. Coating thickness was not a calculated value in this case. The
coating
looks dense and tightly attached to the substrate, and only a small amount of
coating close to the substrate was broken off during grinding and polishing
processes. Coating thickness at 10 hours of coating was determined to be about
33 pm as indicated by energy dispersive X-ray spectroscopy (EDX) based on
analysis of Ca content.
Relationship Between Calculated and Observed Coating Thickness:
A comparison between calculated and observed coating thicknesses was
undertaken. Coating experiments were conducted in which activation was done at
room temperature in a 10 M NaOH solution at a constant DC voltage of 10 V for
30
minutes. Coating was performed at pH 6.50 at a temperature of 37 C in a
deposition solution as described in the procedure for coating above. The
deposition solution was replenished every half hour. Results are provided in
Fig. 7
and Table 2. Minimum observed coating thickness is much greater than
calculated
thickness and appears to be linearly related to duration of coating.
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Table 2
Time of Coating Calculated Coating Observed Coating
(hours) Thickness (pm) Thickness (pm)
0.5 0.04 ---
1.0 0.90 4.5
2.0 2.05 6
3.0 3.44 10
4.0 3.60 13
5.0 5.63 20
Characterization of HA Coatings:
HA coatings on Ti6AI4V substrates produced in accordance with the present
invention are of very high purity and are strongly bonded to the substrate.
Strong bonding between the coating and the substrate results from formation of
a
strong initial layer with inter-diffusion of elements from both the substrate
and the
coating. EDX line analysis conducted as a line scan perpendicular to the
boundary
line from the coating to the substrate confirms the existence of a 2-3 pm
thick initial
diffusion layer close to the substrate. EDX analysis conducted as a line scan
parallel to the boundary line between the coating and the substrate further
confirms
that the initial diffusion layer is an inter-diffusion layer of Ti, Ca and P.
EDX point analysis also confirms that the inter-diffusion layer exists.
Referring to Fig. 8, a scanning electron micrograph shows a cross-section of a
coated substrate with locations of EDX point analysis measurements 1-5
indicated
thereon. Substrate 11 is coated with hydroxyapatite 12 which is covered with a
layer of expoxy resin 13. The results of EDX point analysis on the
hydroxyapatite
(HA) coating and corresponding ratios of Ca/P are listed in Table 3.
CA 02550457 2006-06-15
Table 3 - EDX analysis (atomic percentage) of coating
Measurements C 0 P Ci Ca Ti V Ca/P
1 67.77 16.43 5.81 0.52 9.47 1.63
2 58.04 18.72 8.33 0.56 14.35 1.72
3 21.80 21.47 51.55 5.19 N/A
4 32.71 25.72 5.25 21.47 13.68 1.23 4.08
64.56 18.11 6.36 0.36 10.59 1.67
Measurement 4 shows that Ca, Ti and V co-exist at the initial coating layer.
Since Measurements 1, 2 and 5 are away from the inter-diffusion layer, EDX
5 analysis of these points is not influenced by the substrate and the ratio of
Ca/P
should be the actual ratio of Ca and P existing in the coating. The average of
Measurements 1, 2 and 5 is 1.67, which is exactly the atomic ratio of Ca/P in
stoichometric hydroxyapatite (CaIo(PO4)6(OH)2). This confirms that the formed
coating is pure HA.
Measurements 3 and 4 are influenced by the inter-diffusion layer and the
Ca/P ratio is far away from hydroxyapatite. There is no P detected at
Measurement
3 and much more Ca than P is detected at Measurement 4, possibly indicating
that
Ca first reacts with titanium oxide and favorably deposits on the substrate at
the
activated substrate surface as amorphous CaTiO3, while the P participates at a
later stage as the CaTiO3 incorporates phosphate ion to form hydroxyapatite on
the
surface. Measurement 3 is closer than Measurement 4 to the substrate, thus
there
is no P detected at Measurement 3. P gradually deposits and is detected at
Measurement 4.
X-ray diffraction (XRD) analyses of commercial crystallized hydroxyapatite
powder (PENTAX Corporation, Tokyo, Japan) and of powders obtained from
coatings of the present invention confirm that the coatings of the present
invention
are substantially pure hydroxyapatite (HA). The commercial HA XRD pattern
matches very well with the standard XRD pattern of HA in the JCPDF card (Joint
Committee on Powder Diffraction Standards - Powder Diffraction Files). Major
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patterns of the powders from coatings of the present invention match very well
with
the commercial HA powders.
Coatings formed on substrate surfaces were analyzed with a Perkin Elmer
FTIR (Fourier Transform Infrared Spectroscopy) Instrument (Spectrum BX), in a
scanning range between 4000 cm-1 and 400 cm-1 with 216 scans per sample.
Spectra obtained show characteristic bands of HA along with additional bands
ascribed to associated H20.
Characteristic FTIR bands of hydroxyapatite corresponding to the stretching
vibration of P043" can be observed in the range of 1200-900 cm-', which in
this
investigation are at 1119 cm-1, 1048 cm-', 1036 cm-1 and 979 cm'. Deformation
vibrations of P043- are at 603 cm-1, 572 cm"', 471 cm-1 and 422 cm-1. Hydroxyl
(OH-) bands are at 3458 cm-1 and 617 cm-'. Bands located in the range of 3900
cm-
1 to 3500 cm-1 and 1900 cm-1 to 1400 cm-1 can be assigned to associated H20 in
the
coating, the result of a long period of exposure in the atmosphere.
With increasing duration of coating, intensities of the hydroxyapatite FTIR
bands significantly increase, indicating a significant increase in coating
thickness
starting from a time of about 180 minutes. The characteristic bands of HA
split after
about 180 minutes, indicating that the formed HA may be starting to
crystallize.
Broad and not-split bands of HA at 120 minutes illustrate that the initially
deposited
HA is in an amorphous or poorly crystallized phase. The characteristic FTIR
band
of C032- is not very intense up to about 120 minutes of coating, and is
significantly
more intense after 180 minutes of coating, indicating an increase in carbonate
content as coating proceeds.
Scanning electron microscopy (SEM) of the formed HA coating (Fig. 9)
shows that pore sizes of the coating are on the nano-scale. Pore diameters are
on
the order of 200-500 nm.
Diffraction pattern from transmission electron microscopy (TEM) analysis
(Fig. 10a) shows that the formed HA coating is crystalline with a measured d-
spacing that matches pure HA. The formed HA coating has nano-scale grain size
of
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less than 20 nm (Fig. 10b). Morphologies of a single HA plate also show that
the
grain is less than 20 nm in size (Fig. 10c).
Heat Treatment:
HA-coated Ti6AI4V substrates were prepared by coating an activated
substrate of Example A31 using the Procedure for Coating described above.
Coated substrates were heat treated in a furnace (Pyradia, Quebec, Canada) in
air
for 1 hour. Heat treatment experiments were performed at temperatures of 350
C,
450 C, 550 C, 650 C, 750 C and 850 C.
Fig. 11 is a graph of coating adhesion strength (MPa) as a function of heat
treatment temperature ( C) for heat-treated HA-coated substrates. A repeated
testing confirmed the trend and the values of adhesion strength. Adhesion
strength
increased dramatically between temperatures of about 350 C and about 550 C
from about 9 MPa to about 31 MPa, an increase of about 3 to 4 times. Heat-
treatment at 650 C and above can lead to powdering of the coating, rendering
the
coating more brittle and more easily broken off.
Scanning electron microscopy (SEM) analysis before and after heat-
treatment indicate that surface morphologies are similar before and after heat-
treatment at temperatures in a range of from about 350 C to 550 C. After a
temperature of 650 C, heat-treatment widens cracks on the surface of the
coating
and the coating becomes porous. Widening of cracks may be a result of a
mismatch between the coefficients of thermal expansion (CTE) of the Ti6AI4V
substrate, Ti02 and HA layers. Heat-treatment may cause a small amount of
contraction between the substrate and the Ti02 layer, while large expansion
between the Ti02 layer and the HA layer may result in severe stresses, which
may
be released by cracking.
X-ray diffraction (XRD) patterns of heat-treated and untreated samples
indicate that crystallinity of the HA coating increases at temperatures of 450
C and
550 C with the appearance of new peaks. At 650 C one new phase appears,
which was found to be tricalcium phosphate (TCP), and the coating is mixture
of HA
and TCP. With increasing temperature beyond 650 C, the concentration of TCP
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increases. TCP is more readily dissolvable than HA in human body fluids, thus
the
formation of the TCP is not favorable for medical applications. SEM
observations
also show that heat treatment at and above 650 C can cause some morphology
changes.
Fracture surface analysis of hydroxyapatite (HA) coatings with and without
heat-treatment after adhesion testing indicates that some of the coating still
adheres to the substrate, i.e. fractures happen inside the coating instead of
between the coating and the substrate, indicating that bonding is strong
between
the coating and the substrate. More of the coating adheres to the substrate
with an
increase in heat-treatment temperature, indicating that bonding becomes
stronger
with an increase on heat-treatment temperature, i.e. heat-treatment
strengthens the
bonding between the coating and the substrate.
Incorporation of Protein Into HA Coatings:
Attempts were made to incorporate Bone Morphogenic Protein (BMP2) into
HA coatings on Ti6AI4V substrates at concentrations of BMP2 of 1 pg/L, 10 pg/L
and 50 pg/L by the following general procedure. Step 1: Coating of activated
Ti6AI4V substrates was performed in 175 ml beakers for 2 hours with a regular
deposition solution without addition of protein. The deposition solution was
replenished at half hour intervals. Step 2: Further coating of coated
substrates
from Step 1 was performed in 50 ml beakers for 3 hours with addition of
protein at
different concentration. The deposition solution was replenished at one hour
intervals. For comparison, other coated substrates from Step 1 were further
coated
with HA under various conditions without addition of protein. Coating
conditions
are listed in Table 4 and the coating weight gain is listed in Table 5.
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Table 4
Sample Step 1 Step 2
coating solution coating solution
interval interval protein
time (h) volume time (h) vol. (pg/L)
(h) (ml) (h) (mi)
P1 2.0 0.5 75
P2 2.0 0.5 175 3.0 1.0 175 0
P3 2.0 0.5 175 3.0 0.5 50 0
P4 2.0 0.5 175 3.0 1.0 50 0
P5, P6 2.0 0.5 175 3.0 1.0 50 1
P7, P8 2.0 0.5 175 3.0 1.0 50 10
P9, P10 2.0 0.5 175 3.0 1.0 50 50
Table 5
P1 P2 P3 P4 P5 P6 P7 P8 P9 P10
Weight ain
(mg/cm~) 0.67 1.87 1.28 1.08 1.15 1.35 1.15 1.15 1.14 1.30
Average 0.67 1.87 1.28 1.08 1.25 1.15 1.22
SEM indicates that all coatings from Step 1 have a bone-like morphology.
For Step 2, SEM indicates that the morphology of HA coatings after coating
with
solutions having protein at concentrations of 1pg/L and 10 pg/L is fine and
hairy,
but the protein is not present in the coating. SEM indicated that the addition
of
50pg/L of protein significantly changed the morphology to a very fine bone-
like
structure with a large presence of protein. It appears that incorporation of
protein
into the HA coating may be initiated at a certain minimum concentration of
protein.
High SEM magnification indicates that protein and HA mingle together in the
coating, which is good to sustain protein in the coating. Heat treatment of
coatings
containing protein may result in protein denaturation or pyrolysis.
Coating of Ti-HDPE Composite:
CA 02550457 2006-06-15
A Ti-composite was fabricated by infiltrating high density polyethylene
(HDPE) at elevated temperature into a porous Ti disk, which was sintered from
micro-scale Ti powders. The disks were polished using #400 SiC paper to form a
flat surface, and then the disks were subjected to sand-blasting on all the
surfaces
using #10 alumina powders. To make a through activation on the disks due to
the
porosities, the activation process was performed for 45 minutes. A regular
Ti6AI4V
alloy was subjected to the same treatments and coating procedures.
Table 6 shows the weight gain of hydroxyapatite after coating process. More
HA coating formed on porous Ti and Ti-HDPE composite disks than on the regular
Ti6AI4V alloy. More HA coating formed on the porous Ti than on the Ti-HDPE
composite, possibly due to its greater porosity in which some NaOH was
trapped,
resulting in a more alkaline surface, which is favorable for the formation of
HA
coating on the surface. Even though more HA coating formed on porous Ti, the
surface is not fully covered and the coating is not even. HA coatings on
porous Ti
have some uncovered areas on the bottoms, and it is difficult to form coatings
on
the edges and surrounding surfaces. In contrast, HA coating is evenly
distributed
on the surface of Ti-HDPE composite disks, with the bottoms, edges and
surrounding surfaces all fully covered.
Table 6
Material Ti6AI4V Ti-HDPE Composite Porous Ti
Sample S1 S2 S3 S4 S5
Weight Gain 1.198 1.594 1.619 2.080 3.181
(mg/cm2)
Average Weiqht 1.198 1.607 2.630
Gain (mg/cm )
Other advantages that are inherent to the structure are obvious to one skilled
in the art. The embodiments are described herein illustratively and are not
meant
to limit the scope of the invention as claimed. Variations of the foregoing
embodiments will be evident to a person of ordinary skill and are intended by
the
inventor to be encompassed by the following claims.
26
