Note: Descriptions are shown in the official language in which they were submitted.
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Proce.ss for producing a graduated coating of calcium phosphate phases and
metallic
oxide phases on metal implants
The invention refers to a process for producing a gradient coating containing
calcium phos-
phate phases and metal oxide phases on metallic implants, especially on
titanium or titanium
alloys, for use as dental, maxillofacial or joint implants.
It is well known that the time of ingrowth of a metallic implant until full
mechanical loadability
is achieved can be reduced if the metallic implants have been coated with
calcium phosphate
phases, especially with hydroxyapatite, a calcium phosphate phase similar to
bone.
The connection between the metal implant and calcium phosphate can be realized
in different
ways. According to EP-A 0006544, spherical calcium phosphate particles are
molded in a
model together with the implant material. In US-PS 4.145.764 a process is
described in which
ceramic particles are thermically sprayed onto an implant. However, these
techniques are very
energy intensive, expensive and time consuming. Further, from EP 0232791 and
EP 0237053
processes are known, in which a resorbable calcium phosphate ceramic is
deposited on tita-
nium by means of anodic oxidation under spark discharge in an aqueous
electrolyte solution.
However, the so produced coating does not consist of hydroxyapatite or
fluorapatite but of oxides and strongly resorbable calcium phosphate phases.
With a complete resorption of the
calcium phosphate phases also the bioactive character of the implant is lost.
DE 43 03 575 C 1 describes a process for producing apatite coatings on metal
implants by in-
ducing a plasma-chemical reaction by means of alternating current in aqueous
solutions. An
electrolyte solution is used made from the salts of alkali or alkaline earth
metals, in which hy-
droxyapatite and/or fluorapatite is dispersed with a defined grain size and
concentration. The
plasma-chemical process leads to coatings which consist of pure hydroxyapatite
or fluorapatite
with an extent of up to 95 %.
Disadvantages of this process are, especially, the large thickness of the
coating (up to 250 m)
as well as the coarse grain size of the coating (up to 100 m). Furthermore,
the bonding
strength between the coatings and implants is not optimal.
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WO 92/13984 describes a process of the deposition of bioactive coatings on
conductive sub-
strates. An electrolyte cell contains an inert anode and an electrolyte
consisting of an aqueous
solution of ions of the ceramic, having a pH value of less than 8. The
activated conductive sub-
strate is dipped into the electrolyte solution and the potential between the
anode and the con-
ductive substrate is chosen such that a ceramic layer is deposited on the
conductive substrate
based on the pH rise at the boundary between electrolyte and conductive
substrate.
A disadvantage of this solution is that'the deposition of the layer proceeds
only on the surface
of the substrate. This means, on the one hand, that there is no mechanically
loadable connec-
tion. On the other hand, the coating can be completely resorbed biologically.
Furthermore, the
coating always consists of three components, a- and 0-tricalcium phosphate and
components
of the chemical formula Ca5(PO4)3_x(C03)x(OH),+x with X = 0.2 or less. This
means that the
coating is always a mixture of these components not approximating the
composition of bone.
The object of the invention is the coating of metallic implants, preferably of
titanium implants
or implants made of titanium alloys, with a gradient layer made of calcium
phosphate phases
and metal oxide phases. Thus, in addition to the effect of accelerated
ingrowth a permanent
improvement of the interaction between the implant surface and the biological
system will be
achieved. Moreover, the composition of the calcium phosphate phases is
controllable via the
process parameters so that, optionally, hydroxyapatite, octacalcium phosphate
or brushite as
well as defined combinations of these phases can be produced.
According to the invention, there is provided a process for producing a
gradient coating of
calcium phosphate phases and metal oxide phases on a metal implant,
comprising: providing a
metal implant; providing an electrolyte solution containing calcium phosphate
ions, and having
a pH of between 4.0 and 7.5; providing a counter electrode in the electrolyte
solution; placing
the implant in the electrolyte solution; applying an electrical potential
between the counter
electrode and the implant, so that the implant initially acts as a substrate
cathode; periodically
reversing the polarity of the electrical potential a plurality of times, so
that the implant
alternates between cathodic polarization and anodic polarization, to deposit a
gradient coating
of calcium phosphate phases and metal oxide phases on the implant.
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Preferably, the ratio of the concentration of the calcium and phosphate ions
is chosen such that
it is equal to their concentration ratio.in hydroxyapatite. In a preferred
implementation of the
invention the electrolyte is produced from an aqueous solution of CaCl2 and
NHaH2POa with a
ratio of concentration of calcium and phosphate ions equal to that of
hydroxyapatite. The pH
value is preferably adjusted between 4 and 7.5 by means of a diluted 1VH4OH
solution. The use
of other readily soluble calcium salts and phosphates (for example, alkali
phosphates) is also
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possible. Beyond that the conditions of the electrolysis mainly determine the
formation of par-
ticular calcium phosphate phases and their mixtures, respectively. It is also
possible to choose
different concentration ratios of calcium and phosphate ions.
In an arrangement consisting of a substrate electrode, reference electrode and
counter elec-
trode the substrate electrode formed by the implant is polarized varying the
polarization from
cathodic to anodic and vice versa. l'referably, the substrate electrode is
polarized cathodically
in the first step. In repeating steps anodic and cathodic polarizations are
added, preferably fin-
ishing the deposition with a cathodic polarization of the substrate electrode.
It: is advantageous to raise the time periods of the cathodic and anodic
polarizations during the
repeating steps and/or to carry out the anodic polarizations with a potential
becoming more
and more anodic. Cathodic and anodic polarizations of the substrate electrode
are executed
aiternately with a total cathodic polarization time of between I and 60 min
and a total anodic
polarization time of between 1 and 60 min.
The cathodic polarization can be realized potentiostatically or
galvanostatically and the anodic
polarization can be realized potentiostatically, potentiodynamically or
galvanostatically until
the desired target potential is reached. The target potential is in the region
of 2 to 150 VSCE.
The choice of the target potential determines the thickness of the titanium
oxide layer to be
built up and, hence, the thickness of' the gradient region of the coating.
The current density of the cathodic galvanostatic polarization is preferably
chosen to be 0.1 to
mA/cmZ.
The three-electrode arrangement for the execution of the process according to
the invention, is
made of a saturated calomel electrode as the reference electrode, a platinum
sheet as the
counter electrode, and the metallic implant as the substrate electrode. A
thermostatically con-
trolled cell is used as the electrolyte cell. The electrochemical reaction is
carried out preferably
at a temperature of 60 C.
W'ith the help of the process described by the invention, the desired calcium
phosphate phase
or the defined mixture of calcium phosphate phases can be built up from the
used electrolyte
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solution as a gradient structure with ttie metal oxide of the implant
material. The coating de-
posited on the metal implant induces a good growing of the bone towards the
implant sup-
porting the incorporation of the implant into the biological system. Under the
influence of sub-
stances of the body the coating is normally resorbed. To give the bone an
orientation through-
out the whole lifetime, calcium phosphate particles are not only fixed to the
implant, but also
i.nserted in it. This is possible because of the step-by-step process of the
cathodic and anodic
polarization of the substrate electrode. The desired calcium phosphate phase
or mixture of
phases is deposited on this substrate electrode from the electrolyte during
the cathodic polari-
zation. During the anodic polarization the oxide layer of the implant metal
begins to grow over
t:he deposited calcium phosphate particles, which results in their
incorporation into the oxide
layer of the metal. Repeating these steps increases the thickness of the
layer. It is advantageous
for the growth of the layer to raise the time periods of the steps and to
carry out the second
step with a potential becoming more and more anodic. To obtain a surface layer
of calcium
phosphate phases, finishing the process of making the gradient layer with a
cathodic polariza-
tion is advantageous.
The advantages of the deposited layers according to the invention are an
improved transmis-
sion of forces and a permanent improvement of the biocompatibility by means of
the incorpo-
ration of calcium phosphate phases in the implant surtace. The possibility of
the adjustment of
the composition of the layer to the composition of the inorganic bone
substance a quick in-
growth into the bone is supported.
The invention is explained in more detail by means of the following examples:
F?xample I
A disc made of 99.7% pure titaniutn having a diameter of 13 mm and a thickness
of 2 mm is
ground, cleaned in alcohol, rinsed in deionized water and dried with a fan. As
the electrolyte
solution a calcium phosphate solution is used, produced as follows: 10 mi
stock solution of
CaCl2 = 2H20 and NH4H2PO4, in concentrations of 33 mM and 20 mM, respectively,
are di-
luted and mixed, resulting in 200 ml of 1.67 mM calcium and 1 .0 mM phosphate.
Previously,
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the pH value is adjusted using diluted NH4OH solution to 6.4 The solution is
heated to 60 C
and poured into a double jacket cell. A three-electrode arrangement is set up.
A saturated
calomel electrode is used as a reference electrode. A platinum sheet is the
counter electrode.
~I'he titanium disc forms the working electrode. After this the potentiostat
is contacted. The
formation of the hydroxyapatite layer is realized through an alternating
polarization:
min cathodic polarization of the titanium sample, galvanostatically, with I =
1 mA (ls' step);
10 min anodic polarization, potentiostatically, with U== 5 VSc~E (2 d step);
min cathodic polarization according to step I(3"d step);
10 min anodic polarization with U= 10 VSCE (4'h step);
finishing with 35 min of cathodic polarization according to the lY' step (5'~'
step).
The sample is removed from the electrolyte, rinsed with deionized water and
dried with a fan.
The deposited layer looks whitish yellow, is uniformly developed and has a
good interface
bonding. Investigations carried out with a scanning electron microscope
revealed a closed
coating, consisting of agglomerates of very fine needles having a length of
about 500 nm. The
analysis of the composition by means of energy dispersive X-ray analysis
showed a Ca/P ratio
oPthe phase in the coating equal to that of commercial hydroxyapatite. X-ray
diffraction analy-
sis verified the phase to be hydroxyapatite.
The wedge-shaped preparation shows a gradient structure of the coating. Under
the scanning
electron microscope no sharp transition between substrate and coating is
observed.
Example 2
An electrolyte identical to that of example I is used. The titanium disc is
prepared according to
example 1. The electrochemical setting is equal to example 1. After a
galvanostatic, cathodic
polarization (I = 0.3 mA, 10 min) (1 g' step), the 2 d step is carried out
starting with the poten-
tial set up by the process of the galvanostatic, cathodic polarization, as an
anodic polarization
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at a polarization rate of 5 mV/s until a level of 5 VscF; is reached. After
having reached this
potential a cathodic polarization with 0.3 mA is carried out in step 3.
Starting with the poten-
tial set up by the process of the galvanostatic, cathodic polarization, the
40' step is an anodic
polarization with a polarization rate of 5 mV/s until a level of 10 VSCE is
reached. The process
is finished with a cathodic polarization of 3 5 min according to the 1 st step
(5'" step).
T'he coating on the substrate electrode consists of octacalcium phosphate.
Electron micro-
scopical investigations show crystals with shapes from needles to bands with
dimensions up to
m. X-ray diffractornetric and raman spectroscopic analyses done for
comparison, show that
the coating is made of octacalcium phosphate.
The wedge-shaped preparation shows a gradient transition in the phase
boundary. Under the
scanning electron microscope no sharp transition between substrate and coating
is observed.
Example 3
A titanium disc is prepared according to example i. 200 ml of calciumphosphate
solution are
used as an electrolyte solution with the following composition realized by
weighing in the salts:
40 mM CaClz and 25 mM 1VH.,HZP04. The pH value is adjusted to 4.4.
The electrochemical arrangement is equal to example I
After the first potentiostatic cathodic polarization with UscF =-1300 mV, 10
min (step 1), the
electrode is anodically polarized under galvanostatic conditions in a second
step, 1 mA, 10
min. After 15 min of cathodic polarization according to step I(3rd step), the
galvanostatic
anodic polarization is done in a 4"' step for 10 min with 2 mA. The process is
finished with a
cathodic polarization of 35 nun according to step 1(5'h step).
The coating on the substrate electrode consists of crystals having the shape
of small plates and
dimensions up to 30 m.
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Energy dispersive X-ray analysis gives a Ca/P ratio of the phase in the
coating equal to that of
commercial brushite. X-ray diffract.ion revealing the crystal structure
confirms that the phase is
hydroxyapatite.
The wedge-shaped preparation shows a gradient transition in the phase
boundary. Under the
scanning electron microscope no sharp transition between substrate and coating
is observed.
Example 4
An electrolyte identical to the one of example 1 is used. The titanium disc is
produced accord-
ing to example 1 and, additionally, polished until a mirror-like surface is
obtained, and is oxi-
datively etched in 50 ml of a solution consisting of 0.5 M. NaOH and 0.1 M
H202 for 4 min at a
temperature of 65 C. Under the electron microscope, the etched surface shows a
varying cor-
i-osion of the titanium crystallites and a structure in the nanometer range.
Deposition of the
coating takes place in the same way as in example 1. Electron microscopic
analysis shows the
needle-like crystals as in example 1 with the Ca/P ratio of hydroxyapatite.
Altogether, the
coating has a higher roughness. The coating shows a better ititerface bonding
to the substrate
than in example 1. The wedge-shaped cut shows, in addition to the graduated
transition, an
interlocking between substrate and coating.
