Note: Descriptions are shown in the official language in which they were submitted.
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Field of the Invention:
This invention relates to a conductive substrate and, in
particular, to a conductive implantable device coated with
a bioactive composite coating and a process for production
thereof. The composite coating is comprised of two distinct
layers: a base layer composed of an oxide to minimize metal-
ion release from the substrate and a top layer which is
essentially composed of a calcium phosphate ceramic material
to enhance surface bioactivity. The article coated with this
composite coating is useful as an implantable device such as
artificial hip joints and tooth roots.
Background of the Invention:
Medical devices such as joint prostheses have been commonly
implanted into the skeletal structure of humans to replace
missing or damaged skeletal parts. It is often intended that
these implants become a permanent part of the body. In such
cases, it is important that the prosthesis be strongly fixed
to the skeletal bone structure. Cementless fixation of
permanent implants has become a widespread surgical procedure
which aids in avoiding some of the late complications of cemented
prostheses. In principal, cementless fixation can be achieved
by bone tissue ingrowth in porous coatings or by bone tissue
apposition on surface structured prostheses. In recent years,
the concept of biological attachment of load-bearing implants,
using bioactive calcium phosphate coatings, has also been
developed as an alternative solution to the difficulties
associated with the mechanical fixation and acrylic cements.
It is known that bioactive coatings such as calcium phosphate
ceramics provide direct bone contact as the implant-bone
interface and provide chemical bonding with the bone structure.
Much of the prior art, however, teaches the use of plasma spray
techniques to form bioactive ceramic coatings. Limitations of
the plasma spray technique include: possible clogging of the
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surface porosity, thereby obstructing bone tissue ingrowth and
possible damage to the ceramic coating and the substrate as a
result of intense heat. Furthermore, the plasma spray technique
is a line-of-sight process that produces a non-uniform coating
when applied to porous and non-regular implants. Thus, a
significant portion of the implant surface remains uncovered and
prone to metal-ion release. The metal-ion release is particularly
of concern in the case of porous coated implants with relatively
large surface areas. For such implants, the chemical and
cellular response of the tissues to metal-ion release may be
critical in determining the extent of new bone formation and
its subsequent bonding to the implant. The inhibition of
apatite formation by various metal-ions including Ti, V and
Al ions and their side effects have been documented.
It is clear, therefore, that there is need for a uniform bio-
active coating with optimum characteristics which, in addition
to enhancing bioactivity, can effectively minimize the metal-
ion release from the substrate. There is also need for a
process which will allow uniform formation of such coatings
in a commercially viable manner.
Brief Statement of Invention:
By one aspect of this invention, there is provided a process
for forming a two layer composite coating on a conductive
implantable device from a single electrolyte bath containing
Ca- and P- containing ions, which significantly improves the
corrosion resistance and bioactivity of the device. The two
layer coating, prepared by the process of the invention, is
comprised of a base layer essentially composed on an oxide,
and an outer layer essentially composed of a calcium phosphate
compound selected from Alpha- and Beta- tricalcium phosphate,
calcium hydroxyapatite, calcium deficient hydroxyapatite,
carbonate- containing hydroxyapatite, fluro-apatite or mixtures
of these compounds.
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The process of the invention includes the steps of:
a) immersing the implantable device in an electrolyte containing
Ca- and P- bearing ions;
b) passing an electrical charge of anodic current through the
electrolyte to the implantable device, the duration of the
anodic charge and the magnitude of the current being
effective to permit the growth of an oxide film on the
implantable device with a desirable thickness;
c) passing the second electrical charge of current through the
electrolyte to the implantable device, the second electrical
charge being a charge of cathodic current having a waveform,
duration, and magnitude effective to allow electrodeposition
of a calcium phosphate coating of desired thickness on the
base layer, and
d) repeating steps (b) and (c) a plurality of times to form a
composite coating on the implantable device comprising an
oxide base layer and a calcium phosphate outer layer of
desirable thickness.
By another aspect of this invention, there is provided an
implantable device having a composite coating formed on, at
least, part of its surface. The composite coating consists of
two layers: a base layer essentially consisting of a metal oxide;
and an outer layer essentially consisting of calcium phosphate
selected from the group consisting of Alpha- and Beta-
tricalcium~-phosphate, hydroxyapatite, Ca- deficient hydroxy-
apatite, C03- containing hydroxyapatite, Fluro-apatite and a
mixture thereof.
A further objective of the invention is to provide a conductive
substrate having a composite coating formed on at least part of
its surface. The composite coating consists of two layers:
a base layer essentially consisting of a metal oxide to improve
corrosion resistance of the substrate; and an outer layer
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essentially consisting of Alpha- and Beta- tricalcium phosphate,
hydroxyapatite, Ca- deficient hydroxyapatite, C03- containing
hydroxyapatite, Fluro-apatite, or a mixture thereof.
Detailed Description of Preferred Embodiments of Invention:
The process of coating implantable devices, implants, and the
like, is conducted according to the present invention, in an
electrolyte solution containing Ca- and P- bearing ions. The
pH of the electrolyte is adjusted between 2 and 8 and most
preferably between 4 and 5. The electrolyte may be prepared
by dissolving calcium phosphate compounds such as Alpha-
tricalcium phosphate or calcium hydroxyapatite in an acidic
solution. The acid may beselected from hydrochloric acid
and/or nitric acid. The electrolyte may also be prepared by
dissolving Ca- and P- containing compounds in water. Examples
of Ca- containing compounds are calcium nitrate and calcium
chloride and examples of P- containing compounds are NH4H2P04
and Na2HP04. The pH of the electrolyte may be adjusted,
preferably between 4 and 5, by the addition of an acid or base.
It is desirable that Ca/P molar ratio of the electrolyte be
maintained between 1 to 2 and most preferably between 1.5 to
1.67. In one preferred embodiment of the present invention,
the electrolyte has a calcium ion concentration of less than
0.1 mole per litre and the Ca/P molar ratio of the electrolyte
is 1.67. The electrolyte may additionally contain ions such as
F-, C03--, HC03-, N03-, Cl-, Mg++, A13+ and ions of platinum
group family to produce coatings with specific chemical compos-
itions. The electrolyte may also contain organic substances
such as proteins and biologically active material such as
collagen and bone morphogenic protein. The electrolyte, further,
may contain dissolved gases such as C2~N2~-~co2` and oxidizing~agents
and wetting agents to improve the quality of the coating. The
temperature of the electrolyte during the process may vary from
about room temperature up to a point reasonably below the
boiling point of the electrolyte, depending on the operating
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pressure. For example, the process may be conducted in an
electrolytic autoclave under the saturation vapour pressures
of the electrolyte between room temperature and 250 degrees
Centigrade.
The process of the present invention can be carried out using a
conventional electrolytic cell, having at least one counter
electrode made of, for example, platinum or graphite and equipped
with a programmable power supply. The programmable power supply
is preferably capable of producing constant voltages and
constant currents of a selectably programmable polarity and
intensity, and programmable "on/off" currents and voltage
signals, pulsed waveform and other desirable waveforms with
selectably programmable frequencies and peak intensities. A
preferred programmable waveform for this process is shown in
Fig.l. The horizontal axis, in this figure, corresponds to
time in arbitrary units and the vertical axis corresponds to the
voltage applied to the electrolytic cell during the process, in
arbitrary units. The voltage waveform, in Fig.l, consists of a
constant voltage, Vl, applied to the cell for a period, tl, to
form the oxide base layer, followed by an "on/off" cathodic
voltage. The on/off cathodic voltage has a peak value, V2, an
"on-period", t2, and an "off-period", t3. During the period,
tl, a charge of anodic current is passed through the electrolyte
to the implantable device. The duration period, tl, and the
voltage, Vl, are selected such that it results in an anodic
charge effective to permit the growth of an oxide with desirable
thickness on the implantable device. It is preferred that the
anodic voltage, Vl, to be about 10 volts and most preferably,
about 5 volts. The time period, tl, is also preferably about
30 minutes.
Referring to Fig.l, the "on/off" cathodic voltage results in
passing a series of electrical charges of a cathodic current
through the electrolyte to the implantable device, which results
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in electrodeposition and crystallization of calcium phosphate
compounds on top of the oxide base layer. The peak voltage,
V2, and the time periods, t2, and t3, are selected such that
the average cathodic current density flowing is about 5 mA/Cm2.
The entire period, during which a series of cathodic charges
is passing to the implantable device, should be sufficient
to permit formation of calcium phosphate coating with a
desirable thickness. Roughly, a time period of 30 minutes
is required to obtain a calcium phosphate coating of about
30 micro-metres.
The process of this invention is applicable both to pure
titanium and to titanium-based alloys, e.g., those containing
alloying constituents such as aluminum &vanadium. Other film
forming metals such as Co-Ni alloys and zirconium based alloys
may also be used as the substrate in this invention. The
article to be coated, according to the process of this
invention, may be suitably cleaned or given a cleaning pre-
treatment through various means using conventional processes.
The article may also be activated using conventional methods.
In one preferred embodiment of the present process, the article
to be coated is first treated with a colloidal titanium-based
surface adjustment agent prior to immersing the article in
the electrolyte and effecting electrolysis. Titanium based
colloidal solutions containing between 10 to 200 ppm of
titanium ions may be employed in conjunctionwith the present
invention. The article to be coated may have a porous
surface or may be roughened by, for example, sand blasting,
etching by chemical or electrochemical means. The surface
of the article may also have micro or macro textures.
In one preferred embodiment of the present invention, the
composite coating obtained by the process of this invention
is treated with an alkaline solution containing calcium ions
to increase the Ca/P molar ratio of the coating. A preferred
solution is 0.001 mole per litre of calcium hydroxide maintained
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at a temperature in the range of 30 -to 80 degrees Centigrade.
The coated article may be simply immersed in this solution for
about 1 hour to obtain a coating with a desirable Ca/P ratio
and to improve the crystal structure of the calcium phosphate
coating.
In another preferred embodiment of the present invention, the
coating obtained by the process of the present invention is
treated with a biologically active substance such as collagen,
bone morphogenic protein or an antibiotic.
In yet another preferred embodiment of the present invention,
the coating obtained by the process of the present invention is
densified and sintered by a heat treatment, for example, in a
vacuum at a temperature between ~00 to 800 degrees Centigrade.
Alternatively, the coating may be densified using hydrothermal
treatment. Desirably, the hydrothermal treatment is conducted in
an autoclave at a temperature between 100 to 200 degrees Centigrade,
under a pressure of about 10 kg/Cm2.
Example #1:
An electrolyte was prepared by mixing 1 litre 0.042 mole per
litre CaC12 2H20 and 1 litre 0.025 mole per litre NH4H2P04
solutions. The pH of the mixed solution, measured at room
temperature, was 4.1. The electrolyte was then transferred to
a conventional electrolytic cell having a capacity of 2.5 litres
and maintained at 65 degrees Centigrade. The cell was fitted
with a graphite electrode acting as a counter electrode of the
cell. The surface of a commercially pure titanium sample 5 cm
long, 1 cm wide and 1 mm thick was mechanically abraded and then
cleaned with methanol, washed with distilled water and dried in
a stream of air. The sample was then immersed in the electrolyte
and an electrical charge of anodic current was passed through the
electrolyte to the sample for 20 minutes. For this purpose, a
DC voltage of 5 volts was applied between the graphite electrode
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and the titanium sample. A base layer composed of a corrosion
resistant oxide film was thus developed on the surface of the
titanium sample. At the end of this period, the polarity of
the cell was reversed and a charge of cathodic current was
passed through the electrolyte to the titanium sample for 30
minutes to form an outer layer of calcium phosphate compound on
the base layer. The cathodic current used had a pulsed - on/off
waveform with a pulse width of 20 msec and a pulse spacing
of 20 msec. The average current density was 2 mA / Cm2. A
composite coating was thus formed on the titanium substrate
having two distinct layers consisting of an oxide base layer
and a calcium phosphate outer layer. The coated sample was
then removed from the cell, washed with distilled water and then
dried in a stream of hot air for 5 minutes. Electron micro-
scopic examinations of the coated substrate were carried out
using a JEOL - scanning electron microscope. At a-rel-a~ively
high magnification ( x 3000), it was observed that the calcium
phosphate outer layer was composed of an interlocking network
of non-oriented plate-like crystals with the largest dimensions
having an average value of 2 - 3 micrometers. The dimensions
of the micropores present in the coating also range from about
2 to 3 micrometers. The results obtained by wet chemical
analysis of calcium phosphate scraped from the sample indicated
that the calcium phosphate outer layer contained about 2 to 3 %
CO3 by weight. The Ca/P molar ratio of the calcium phosphate
outer layer was also found to be slightly less than 1.67. The
X-ray diffraction pattern of the calcium phosphate scraped from
the sample confirmed that the calcium phosphate outer layer had
a crystalline structure with apatitic characteristics similar to
bone apatite. The infrared spectra of the calcium phosphate
coating further supported the X-ray diffraction results. The
IR - spectra was generally similar to those reported for non-
stoichiometric, carbonate-containing hydroxyapatite and bone
apatite. The IR - spectrum indicated relatively small hydroxyl
peaks at 630 and 3570 Cm~l. These peaks are characteristics
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for hydroxyapatite. The bands at 1040 and 1090 cm-l specific
for P04 modes of hydroxyapatite were also apparent in the
spectra. The IR - spectra also indicated bands at 1400 - 1450
and 872 cm-l, which are assigned to carbonate ions. There was
also a broad band in the range of 3000 - 3600 Cm-l, indicative
of adsorbed water.
Example #2:
A composite coating, having an oxide base layer and a calcium
phosphate outer layer, was formed on a titanium substrate
using a procedure identical to the one in example #1. The
coated sample was then immersed in 0.001 mole per litre of
calcium hydroxide solution at 70 degrees centigrade for 1 hour.
The sample was then removed from this solution and dired in a
stream of hot air for 5 minutes. IR - spectra of the calcium
phosphate outer layer of the composite coating obtained,
indicated intense hydroxyl peaks at 630 and 3570 Cm-l.
Example #3:
A composite coating, similar to one in example #2, was prepared
on a titanium substrate. The coated sample was then heat treated
at 400 degrees Fahrenheit for 30 minutes. The IR - spectra of
the calcium phosphate outer layer, subsequent to heat treatment,
indicated very intense OH - peaks and a weak broad band in the
3000 - 3600 Cm-l range.
Example #4:
A composite coating was prepared on a titanium substrate using
an identical procedure as described in example #3 except that
Nitrogen gas was continuously sparged into the electrolyte and
calcium hydroxide solution during the preparation of the coating.
The IR - spectra of calcium phosphate outer layer, in this case,
indicated no significant bands at 1400-1450 Cm-l assigned to
carbonate ions. The IR - spectra, however, indicated intense
hydroxyl peaks at 630 and 3570 Cm-l, characteristics of hydroxy-
apatite. The IR - spectra results, together with the X-ray data
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indicted that the calcium phosphate outer layer was well-
crystallized, stoichiometric hydroxyapatite with no significant
carbonate content.
Example #5:
A composite coating, having an oxide base layer and a calcium
phosphate outer layer, was prepared using an identical procedure
as described in example #4, except that a porous titanium
substrate was used, in this case. Titanium wire (99.9% purity,
0.25 mm diameter) was used to form a porous substrate with an
average pore diameter of approximately 300 micrometres. The
composite coating obtained on this substrate was dense, uniform,
and well adhered to the substrate without clogging the pores
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