U.S. patent number RE35,129 [Application Number 08/138,230] was granted by the patent office on 1995-12-19 for optimization of bone formation at cathodes.
This patent grant is currently assigned to Electro-Biology, Inc.. Invention is credited to James M. Devine, Brian A. Pethica, Anthony J. Varrichio.
United States Patent |
RE35,129 |
Pethica , et al. |
December 19, 1995 |
Optimization of bone formation at cathodes
Abstract
A method including applying varying signals to a first electrode
at the tissue site and a second electrode remote from the tissue
site and monitoring the results to determine a distinctive
transition in the current-voltage characteristics of the electrode
pair. A signal is then selected and applied to the electrodes to
operate beyond the transition. Periodically, a varying signal is
applied to the electrodes and the monitoring process reperformed to
determine a new transition and an appropriate signal is selected to
operate beyond the transition.
Inventors: |
Pethica; Brian A. (Upper
Montclair, NJ), Devine; James M. (Lower Burrell, PA),
Varrichio; Anthony J. (Flanders, NJ) |
Assignee: |
Electro-Biology, Inc.
(Parsippany, NJ)
|
Family
ID: |
24186271 |
Appl.
No.: |
08/138,230 |
Filed: |
October 15, 1993 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
547821 |
Jul 2, 1990 |
05056518 |
Oct 15, 1991 |
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Current U.S.
Class: |
607/2; 607/52;
607/51 |
Current CPC
Class: |
A61N
1/205 (20130101); A61N 1/08 (20130101); A61N
1/326 (20130101) |
Current International
Class: |
A61N
1/20 (20060101); A61N 1/08 (20060101); A61N
001/00 () |
Field of
Search: |
;607/2,3,50,51,52,61,62,66 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Brighton, Carl T. et al., "Electrical Stimulation and Oxygen
Tension," Annals N.Y. Acad. Sci. 238:314-320 (1974). .
Brighton, Carl T. et al., "Cathodic Oxygen Consumption and
Electrically Induced Osteogenesis," Clin. Orthop. Rel. Res.
107:277-282 (1975). .
Spadaro, Joseph A., "Bioelectrochemical studies of Implantable Bone
Stimulation Electrodes," Bioelectrochem. Bioenergetics 5:232-238
(1978). .
Spadaro, Joseph A., "Electrical Osteogenesis--Role of the Electrode
Material," In: Electrical Properties of Bone and Cartilage.
Experimental Effects and Clinical Applications, Brighton, Black and
Pollack, eds., Grune and Stratton, New York, 189-196 (1979). .
Black, Jonathan et al., "Mechanisms of Stimulation of Osteogenesis
by Direct Current," In: Electrical Properties of Bone and
Cartilage. Experimental Effects and Clinical Application. Brighton,
Black and Pollack, eds., Grune and Stratton, New York, 215-224
(1979). .
Brighton, C. T., "Present and Future of Electrically Induced
Osteogenesis," In: Clinical Trends In Orthopaedics Ed: Straub and
Wilson, Jr., Thieme-Stratton, N.Y., 1-15 (1982). .
Baranowski, Thomas J. et al., "Microenvironmental Changes
Associated With Electrical Stimulation of Osteogenesis by Direct
Current", Trans. Bioelectrical Repair Growth Soc. 2:47 (1982).
.
Baranowski, Thomas J. et al., "Mircroenvironmental Changes and
Electrodic Potentials Associated With Electrical Stimulation of
Osteogenesis by Direct Current," Trans. Orthop. Res. Soc. 8:258
2:47 (1983). .
Baranowski, Thomas J. et al., "The Role of Cathodic Potential in
Electrical Stimulation of Osteogenesis by Direct Current" Trans.
Orthop. Res. Soc. 8:352 (1983). .
Baranowski, Thomas J. et al., "The Role of Cathodic Potential in
Electrical Stimulation of Osteogenesis by Direct Current," Trans.
Bioelectrical Repair Growth Soc. 3:34 (1983). .
Baranowski, Thomas J., Jr., "Electrical Stimulation of Osteogenesis
by Direct Current: Electrochemically-Mediated Microenvironmental
Alterations," Ph.D. Thesis, University of Pennsylvania,
Philadelphia, Pa., title page, pp. 62-72, 87-90, 211, 213-217, 233,
244-245 (1983). .
Dymecki, S. M. et al., "The Cathodic Potential Dose-response
Relationship for Medullary Osteogenesis with Stainless Steel
Electrodes," Trans. Bioelectrical Repair Growth Soc. 4:29 (1984).
.
Black, Jonathan et al., "Electrochemical Aspects of d.c.
Stimulation of Osteogenesis," Bioelectrochem. Bioenergetics
12:323-327 (1984). .
Baranowski, Thomas J. et al., "The Mechanism of Faradic Stimulation
of Osteogenesis," In: "Mechanistic Approaches to Interactions of
Electric and Electromagnetic Fields with Living Systems," M. Blank
and E. Findle, eds., Plenum Publishing Corp., New York, 399-416
(1987)..
|
Primary Examiner: Manuel; George
Attorney, Agent or Firm: Woodard, Emhardt, Naughton,
Moriarty & McNett
Claims
What is claimed:
1. A method of stimulating osteogenesis or other tissue repair
processes at a tissue site within a living body comprising:
locating a first electrode at said tissue site within the living
body;
coupling a second electrode to said living body remote from said
tissue site;
applying various signal levels to said first and second electrodes
and monitoring the resulting current flows between the electrodes
to determine a current-voltage characteristic of said
electrodes;
identifying a voltage signal level at which a distinctive
transition occurs in said current-voltage characteristic; and
applying a voltage signal level to said electrodes to cause the
electrodes to operate at a point on the current-voltage
characteristic which is just beyond the point at which said
transition occurs.
2. A method according to claim 1, including periodically applying
said signal levels to said electrodes and monitoring the resulting
current flow between the electrodes to re-determine the location
along said current voltage characteristic of said transition point,
and modifying said voltage signal applied to said electrodes to
cause the electrodes to operate just beyond said newly determined
transition point.
3. A method according to claim 1, wherein said electrodes are
operated at a current level between 10 and 50 microamperes.
4. A method according to claim 1, wherein said first electrode is a
cathode and said second electrode is an anode.
5. A method according to claim 1, wherein said second electrode is
percutaneous.
6. A method according to claim 1, wherein said second electrode is
fully implanted.
7. A method according to claim 1, wherein said second electrode is
located transcutaneous.
8. A method according to claim 1, including:
locating a plurality of first electrodes at said tissue site;
applying said signal levels to said plurality of first electrodes
and said second electrodes and monitoring the resulting current
flows to determine the voltage signal level associated with said
distinctive transition for each of said first electrodes; and
applying a voltage signal level to each of said first electrodes to
cause each of said electrodes to operate just beyond its respective
transition point.
9. A method according to claim 8, wherein
each of first electrodes includes a plurality of conducting ports
at said tissue site; and
wherein said voltage signal level is applied to said electrodes
such that each conducting port carries a current between 10 and 50
microamps.
10. A method according to claim 1, wherein:
said first electrode includes a plurality of conducting ports at
said tissue site; and
wherein said signal level is applied to said electrodes such that
each conducting port carries a current between 10 and 50
microamps.
11. An apparatus for stimulating osteogenesis or other tissue
repair processes at a tissue site in living tissue comprising:
a first electrode adapted to be positioned at said tissue site
within the living body;
a second electrode adapted to be positioned in electrical contact
with said living body;
signal means connected to said first and second electrodes for
applying various voltage signal levels to said first and second
electrodes and for monitoring resulting current flows between the
electrodes to determine a current-voltage characteristic of said
electrodes, and for applying a voltage signal level to the
electrodes to cause the electrodes to operate at a point along the
current-voltage characteristic which is just beyond the point at
which a distinctive transition in said characteristic occurs.
12. An apparatus according to claim 11, wherein said signal means
further comprises:
monitor means for monitoring said current-voltage characteristic
and for recognizing changes in the point at which the distinctive
transition occurs;
control means for causing said signal means to maintain the
operation of the electrodes at a point which is just beyond the
point at which the changed transition occurs.
13. An apparatus according to claim 12, wherein said monitor means
includes timing means for periodically causing said monitor means
to recognize changes in the point at which the transition occurs,
and for causing said signal means to maintain the operation of the
electrodes at a point which is just beyond the point at which the
changed transition occurs.
14. An apparatus according to claim 11, wherein said signal means
provides a current of between 10 to 50 microamperes.
15. An apparatus according to claim 11, wherein said first
electrode is a cathode and said second electrode is an anode.
16. An apparatus according to claim 11, wherein said first
electrode is a percutaneous electrode and said second electrode is
a transcutaneous electrode.
17. An apparatus according to claim 11, wherein said first
electrode is a percutaneous electrode and said second electrode is
a percutaneous electrode.
18. An apparatus according to claim 11, wherein said first and
second electrodes are totally implantable electrodes.
19. An apparatus according to claim 18, wherein said signal means
is totally implantable.
20. An apparatus according to claim 11, further comprising
a plurality of first electrodes adapted to be positioned at said
tissue site; and
wherein said signal means applies a voltage signal level to each of
said first electrodes to cause the electrodes to operate at a point
along its respective current-voltage characteristic which is just
beyond its distinctive transition point. .Iadd.
21. A method of dynamically determining an operating point for
stimulation of osteogenesis or other tissue repair processes at a
tissue site within a living body comprising:
locating a first electrode at said tissue site within the living
body;
coupling a second electrode to said living body remote from said
tissue site;
applying various signal levels to said first and second electrodes
and monitoring the resulting current flows between the electrodes
to determine a current-voltage characteristic of said
electrodes;
identifying a voltage signal level at which a distinctive
transition occurs in said current-voltage characteristic; and
periodically applying said signal levels to said electrodes and
monitoring the resulting current flow between the electrodes to
re-determine the location along said current voltage characteristic
of said transition point..Iaddend. .Iadd.
22. A method of stimulating osteogenesis or other tissue repair
processes at a tissue site within a living body comprising:
locating a first electrode at said tissue site within the living
body;
coupling a second electrode to said living body remote from said
tissue site;
applying various signal levels to said first and second electrodes
and monitoring the resulting current flows between the electrodes
to determine a current-voltage characteristic of said
electrodes;
identifying a voltage signal level at which a distinctive
transition occurs in said current-voltage characteristic;
applying a voltage signal level to said electrodes to cause the
electrodes to operate about a point on the current-voltage
characteristic at which said transition occurs;
periodically applying said signal levels to said electrodes and
monitoring the resulting current flow between the electrodes to
re-determine the location along said current voltage characteristic
of said transition point; and
modifying said voltage signal applied to said electrodes to cause
the electrodes to operate about said newly determined transition
point..Iaddend. .Iadd.
23. An apparatus for dynamically determining an operating point for
stimulation of osteogenesis or other tissue repair processes at a
tissue site in living tissue comprising:
a first electrode adapted to be positioned at said tissue site
within the living body;
a second electrode adapted to be positioned in electrical contact
with said living body;
signal means connected to said first and second electrodes for
applying various voltage signal levels to said first and second
electrodes and for monitoring resulting current flows between the
electrodes to determine a current-voltage characteristic of said
electrodes, said signal means including monitor means for
monitoring said current-voltage characteristic and for recognizing
changes in the point at which the distinctive transition
occurs..Iaddend. .Iadd.
24. An apparatus for stimulating osteogenesis or other tissue
repair processes at a tissue site in living tissue comprising:
a first electrode adapted to be positioned at said tissue site
within the living body;
a second electrode adapted to be positioned in electrical contact
with said living body; and
signal means connected to said first and second electrodes for
applying various voltage signal levels to said first and second
electrodes and for monitoring resulting current flows between the
electrodes to determine a current-voltage characteristic of said
electrodes, and for applying a voltage signal level to the
electrodes to cause the electrodes to operated about a point along
the current-voltage characteristic at which a distinctive
transition in said characteristic occurs, said signal means
including monitor means for monitoring said current-voltage
characteristic and for recognizing changes in the point at which
the distinctive transition occurs, and control means for causing
said signal means to maintain the operation of the electrodes about
the point at which the changed transition occurs..Iaddend.
Description
BACKGROUND AND SUMMARY OF THE INVENTION
The present invention relates generally to electrically-induced
osteogenesis and more specifically to an improved method and
apparatus for optimizing stimulated osteogenesis.
It is known in the prior art to apply a cathode of metal such as
platinum (Pt), titanium (Ti) or stainless steel at a bone site and
an anode at a skin or tissue location near the cathode implant. The
signal is applied to pass currents between the anode and cathode.
Bone formation is said to be particularly favorable at 20
microamperes for single or multiple cathodes as described in U.S.
Pat. No. 3,842,841 to Brighton, et al.
More recently, it has been reported in U.S. Pat. No. 4,519,394 to
Black, et al that optimum bone formation is assisted by maintaining
a current in the range of 0.1 to 100 microamperes per cathode port
and maintaining the cathode port at a voltage substantially
constant in the range of 1.0 to 1.26 volts relative to a
silver-silver chloride (Ag/AgCl) reference electrode implanted or
contacting body tissue. As indicated in FIG. 1 this is a three
electrode system including a percutaneous or implanted cathode 18
having a port 20 positioned at a tissue site 12 of a bone 10. A
transcutaneous anode 22 may be placed on the skin 16 or fully
implanted in muscle or other convenient tissue. A percutaneous or
implanted reference electrode 30 having a port 32 is inserted into
the living tissue 14 at a point remote from the cathode and anode
locations.
The current between cathodes of materials such as stainless steel,
platinum, titanium or carbon and an appropriately chosen anode
rises slowly with applied voltage until a voltage zone is reached
at which the current increases more rapidly for small increases in
voltage. This transition region ("knee") of the current-voltage
characteristic or curve corresponds with the onset of chemical
reactions such as oxygen reduction and hydroxide ion formation in
the region of the cathode. Typically the knee occurs at an
inter-electrode voltage of about 2.4 volts in physiological
conditions for anode-cathode pairs such as stainless
steel-stainless steel. The position of the knee also depends on
tissue impedance (which changes over time) and electrode position,
among other variables.
It is also known from animal experiments that bone accretion occurs
at the cathode and that overly large currents cause bone loss and
necrosis due to local formation of amounts of electrode reaction
Products in excess of the ability of the tissue region to absorb
and disperse them. There is also evidence that with particular
cathodes such as stainless steel or titanium, the entire current
may pass through a region close to the end of the insulation of the
lead accessing the treatment site. Correspondingly, the finding in
animals that 20 microamperes is optimal for the tested cathodes and
cathode geometries will not describe optimum stimulation for other
cathodes and geometries. Furthermore, the prior methods discussed
above for maintaining the cathode voltage in a fixed range relative
to a reference electrode does not necessarily optimize the
voltage-current relationships with respect to the growth process
and have required three electrodes.
Thus it is an object of the present invention to provide a two
electrode system which provides an optimization of the
current-voltage for an osteogenic stimulation.
Another object of the present invention is to provide an apparatus
and method for optimising osteogenic stimulation which adapts for
variation in the tissue impedance and cathode properties over
time.
These and other objects are achieved by applying varying signals to
a first electrode at the tissue site and a second electrode remote
from the tissue site and monitoring the results to determine a
distinctive transition (knee) in the current-voltage
characteristics of the pair of electrodes. A signal is then
selected and applied to the electrodes to operate beyond the
transition. Periodically, varying signals are applied to the two
electrodes and the monitoring process reperformed to determine a
new transition and the appropriate signal is selected to operate
beyond the transition. The current between the electrodes is
typically between 10 and 50 microamps and an appropriate voltage is
selected to operate beyond the transition. In some tissue repair
situations it will be useful to use more than one cathode implanted
in separate positions within the repair region, and each cathode
may be optimised independently as described for single cathodes. In
other circumstances a branched or multiport cathode may be
convenient, and currents typically between 10 and 50 microamps per
branch or port may be chosen at potentials beyond the transition as
determined for the assembly.
Other objects, advantages and novel features of the present
invention will become apparent from the following detailed
description of the invention when considered in conjunction with
the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of a prior art osteogenesis electrode
arrangement;
FIG. 2a is a typical graph of the current-voltage characteristics
of an anode and cathode pair;
FIG. 2b shows the graph of FIG. 2a within the current shown in a
logarithmic scale;
FIG. 3 is a block diagram of a osteogenic stimulator according to
the principles of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
There is evidence that a voltage optimum exists for bone formation
at an inert metal cathode and there is also evidence of an optimum
current for a given electrode. The two optima may be fairly close
together for cathodes of the form used to date by selecting an
appropriate anode material and geometry (electrode length, diameter
and folding). The present invention, for the optimization of both
the current and voltage, is substantially independent of the
materials chosen and number of ports and is capable of adapting to
changes in cathode geometry and of the impedance at the tissue
site.
Referring to the graphs of FIG. 2a and 2b, the voltage applied
between the anode and cathode has a substantial and definite rise
as the current increases until a narrow region is reached beyond
which the current increases rather rapidly for small increments of
the applied voltage. This change in trend is here described as a
transition or knee, corresponding with the onset of chemical
reactions such as oxygen reduction and hydroxide ion formation in
the region of the cathode.
The present invention has determined that optimum parameters for
current-voltage are likely to be at potentials a little above the
knee. The present invention monitors the applied voltage difference
between the anode and cathode for various currents to determine the
knee of the resulting curves.
Over a period of time, the impedance and composition of the region
being treated may change with progression of healing. Thus the
position of the knee on a current-voltage characteristic shifts
with time and must be adjusted to maintain the current-voltage
characteristic beyond the knee.
A system that is illustrated in FIG. 3 includes an anode port 42
and a cathode port 44 connectable to the anode 22 and cathode 18
with the cathode being at the tissue site. A controller 50, for
example a microcomputer, provides a digital signal to digital to
analog device 52 whose output is an analog voltage. This voltage is
applied to the voltage/current converter 46 which provides an
output current to the anode terminal 42. The anode terminal 42 and
cathode terminal 44 are connected to multiplexer 54 which provides,
selectively, the voltage at the anode or the cathode to analog to
digital converter 56. The output of the A/D converter 56 is a
digital signal provided back to the controller 50.
The process is carried out by providing varying signals to the
ports 42 and 44 to produce the varying current-voltage
characteristic graph. Once the knee of the curve is determined for
that period of time, the voltage and current are then set to
operate beyond the knee. Periodically, for example, every twelve
hours, the process is repeated to determine the new current-voltage
characteristic graph and then selecting an appropriate
voltage/current characteristic to operate beyond the knee.
This process is carried out by the controller 50 supplying
increasing values of voltage to the voltage to current converter 46
which provides increasing values of current to the anode electrode
42. Between each value of voltage provided to the D/A converter 52,
the controller 50 reads the cathode and anode voltage with respect
to an internal ground by controlling the multiplexer 54 and the A/D
converter 56. The controller 50 will then compute the change of
voltage per change of current and determined the decreased in
change of voltage per change of current step to determine the
existence of the knee. Once the knee has been determined, the
controller 50 provides an appropriate voltage through the D/A
converter 52 to set the appropriate current to the anode port 42
through the voltage to current converter 46.
The controller 50 has an internal timer which periodically
reinvestigates the location of the knee and varies the appropriate
signal being sent to the electrode. A typical example for the
controller 50 would be a microcomputer 68HC805 by Motorola. The
voltage to current converter may simply be an operational amplifier
receiving on the positive terminal the output of the D/A converter
52 and on the minus terminal the feedback signal from the cathode
port 44.
Although an automatic system is illustrated in FIG. 3, the process
of the present invention may also be carried out with a manual
system. A variable voltage may be provide as an input to the
voltage to current converter 46 and the output from the anode port
42 and cathode port 44 may be provided to a monitor which would
display the voltage-current characteristics. Thus, an operator can
vary the input voltage and determine visually the location of the
knee and thereby set the appropriate signal to achieve the desired
operating characteristics. Periodically, the operator would
reperform this process by changing the voltage input to the voltage
to current converter 46 to redetermine the location of the knee and
thereby set an appropriate voltage input.
Typically, the current range of operation is in the 10 to 50
microamperes range. In some tissue repair situations it will be
useful to use more than one cathode implanted in separate positions
within the repair region, and each cathode may be optimised
independently as described for single cathodes. In other
circumstances a branched or multiport cathode may be convenient,
and currents typically between 10 and 50 microamps per branch or
port may be chosen at potentials beyond the transition as
determined for the assembly.
The cathode may, per example, be stainless steel, titanium or a
carbon cathode whereas the anode may be for example, stainless
steel mesh or a platimum-plated titanium or other inert metals or
other tissue-compatable electrodes such as salt bridge or
conducting polymers. The cathode or anode may be attached to
insulated leads. It should also be noted that the anode may be
placed transcutaneous, percutaneous or totally implanted and that
the cathode may be placed transcutaneously or fully implanted.
Insulated leads which may be attached to the anode or cathode may
also be placed percutaneously or totally implanted. The stimulator
or signal generator may be totally implanted or may be external and
connected to the electrodes by leads or inductivity. It should also
be noted that the present invention is not to be limited to
fractures but to any bone growth process including spinal fusion,
for example.
Although the present invention has been described and illustrated
in detail, it is to be clearly understood that the same is by way
of illustration and example only, and is not to be taken by way of
limitation. The spirit and scope of the present invention are to be
limited only by the terms of the appended claims.
* * * * *