U.S. patent number 3,892,648 [Application Number 05/461,470] was granted by the patent office on 1975-07-01 for electrochemical deposition of bone.
This patent grant is currently assigned to The United States of America as represented by the Secretary of the Navy. Invention is credited to David C. Phillips, Bevil J. Shaw.
United States Patent |
3,892,648 |
Phillips , et al. |
July 1, 1975 |
Electrochemical deposition of bone
Abstract
A method of improving orthopedic implant materials by the
simultaneous elrodeposition of bone and collagen onto a prosthesis
is provided. Collagen fibrils are dispensed in a gelatin medium and
the gelled collagen is dissolved in a water-glycerine solution.
Finely divided bone particles are then added to this solution and,
by applying a voltage to a pair of electrodes immersed in the
solution, adherent bone and collagen coatings of preferably 1-5
mils thickness are formed on the cathodic electrode.
Inventors: |
Phillips; David C. (Pittsburgh,
PA), Shaw; Bevil J. (Murrysville, PA) |
Assignee: |
The United States of America as
represented by the Secretary of the Navy (Washington,
DC)
|
Family
ID: |
23832693 |
Appl.
No.: |
05/461,470 |
Filed: |
April 16, 1974 |
Current U.S.
Class: |
204/480; 606/86R;
204/483; 204/489; 623/923; 128/DIG.8; 606/76 |
Current CPC
Class: |
A61F
2/30767 (20130101); C25D 13/00 (20130101); Y10S
128/08 (20130101); A61F 2310/00958 (20130101); Y10S
623/923 (20130101) |
Current International
Class: |
A61F
2/30 (20060101); C25D 13/00 (20060101); A61F
2/00 (20060101); C23b 013/00 () |
Field of
Search: |
;204/18R,181,299
;3/1,1.9-1.913 ;128/92C,92CA,92D |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Mack; John H.
Assistant Examiner: Prescott; A. C.
Attorney, Agent or Firm: Sciascia; R. S. Vautrain, Jr.; C.
E.
Claims
What is claimed is:
1. A method of forming a prothesis for bone repair or replacement
comprising:
electrodepositing finely divided powdered bone particles from
aqueous glycerin and collagen dispersions onto a metallic substrate
to form the prosthesis as a coating on the substrate; and
removing the metallic substrate by dissolution during and after
formation of the prosthesis.
2. The method of claim 1 wherein said aqueous glycerin and collagen
dispersions comprise translucent, viscosity-time stable,
thixotropic pseudoplastic gels having a pH in the range of from 2.5
to 4 for suspending said bone particles.
3. A method of producing an orthopedic implant for enhancing bone
repair rates in bone bridge and other bone repair operations
comprising:
dispensing collagen fibrils in a gelatin medium formed from the
class of hydrophilic materials which includes methanol, glycerin,
formamide, dimethylsulfoxide, ethanol solutions of up to
substantially 40% alcohol/60% water by weight, isopropanol solution
of up to substantially 40%/60% water by weight;
dissolving the medium in a water-glycerin solution of 50% water and
50% glycerin by weight;
adding finely divided bone particles to the solution;
immersing a pair of electrodes one of which is a metallic substrate
for a bone prosthesis in the solution;
applying a voltage to said electrodes wherein the metallic
substrate is the cathode; and
forming coatings of bone and collagen on said substrate to a
thickness of from 1 to 5 mils.
4. The method of claim 3 wherein said bone particles are dispersed
in a gel matrix,
said matrix suspending said particles uniformly throughout said
medium.
5. The method of calim 4 wherein said medium comprises a
microcrystalline collagen in the form of a water insoluble partial
acid salt of edible bovine collagen,
said gel produced from said medium containing particles
substantially less than one micron in any dimension.
6. The method of claim 5 wherein said collagen is a polypeptide
collagen having a high molecular weight which is attained by
sub-micron micrycrystalline containing highly polar groups such as
NH, NH.sub.2, and OH.
7. The method of claim 6 wherein said gel is prepared by attriting
collagen fibers in said medium for a period of from 15-30 minutes
in a blender;
said fibers allowed to soak for 5 minutes in said medium and
thereafter attrited to maintain a controllable vortex.
8. The method of claim 7 wherein the resultant gel is filtered
through a sintered glass filter to remove the larger undispersed
fibrils and particle aggregates;
a selected amount of powdered bone added to said gel,
said gel further agitated so as to obtain a suspension of finely
divided bone in the gel matrix of microcrystalline collagen.
Description
The present invention concerns the improvement of orthopedic
implant materials and, more particularly, the cathodic formation of
bone coatings on prostheses by electrodeposition thereon of finely
divided bone particles.
Attempts to understand and correct the failures of orthopedic
implants have revealed that such failures apparently are caused by
fatigue, over-stressing, stress corrosion, etc., among other
causes, and that many desirably strong materials are unsuitable
because they are either directly or indirectly toxic to the host.
One of the most difficult areas of orthopedic replacement is in the
femur head where the stresses have been estimated to be up to four
times the weight of the body. This area is one of the most common
points of failure in the human body and, consequently, an urgent
need exists for a sturdy and durable prosthesis for use therein.
Another area in which total replacement of bone is necessary is
that of damage from gunshot wounds. Here, since the bone does not
appear to always grow along the prosthesis filling the gap, only
occasional success has been achieved.
Some metallic implants such as the cobalt-chromium-molybdenum alloy
Vitallium have proved to be generally satisfactory, exhibiting the
additional advantage of case-hardening with use. Such metallic
implants reduce to a minimum the mechanical wearing problem which
occurs between the replacement of the hipcup, or acetabulum, and
the femur head prosthesis. The high density polyethylene which may
be used as a lubricant between these working parts provides for a
low wearing rate, a resistance to creep, and an absence of toxic
effect. However, there are disadvantages to the use of such
material for this kind of metallic prosthetic device since both 316
stainless steel and cobalt-chromium-molybdenum implants may be
carcinogenic in rats. There are also disadvantages to the use of
methylmethyacrylate as a bearing material in the acetabulum since
methylmethacrylate deteriorates in the human body. There is thus an
unfilled need for a hard, load bearing, smooth material for the
femur head and acetabulum which the present invention
satisfies.
Certain ceramics have been found to be totally inert in the body,
and porous ceramics having a bone size of .about.200.mu. have been
found to accept the growth of bone tissue so that the ceramic
implant may become an integral part of the bone. Since ceramics are
brittle in nature and, therefore, have a limitation for prosthetic
use, the combination of a structural metallic base material and a
ceramic coating appears to present a solution to the problem of
achieving extreme strength in a prosthesis while avoiding any toxic
effects on the body.
The present invention, in general, provides a method of
electrochemically depositing bone particles and collagen onto the
external surface of bone prostheses to stimulate bone attachment.
Collagen fibrils are dispensed in a gelatin medium by dissolving
the gelled collagen in a water-glycerine solution and thereafter
adding finely divided bone particles. A voltage applied to a pair
of electrodes immersed in the solution causes the formation on the
cathode of a bone and collagen coating of from 1-5 mils thick.
Accordingly, it is an object of the present invention to provide a
method of enhancing bone growth on prostheses by the coating
thereof with bone and collagen.
Another object of this invention is to provide a method of forming
prostheses by an electrochemical process wherein bone and collagen
are deposited simultaneously in controlled thickness to form a
non-toxic coating.
A further object of this invention is to provide an improved method
of adhering bone particles to a metallic base to form a prosthesis
which has the required strength, especially for bone sockets, and
is not toxic to the human body.
Other objects, advantages and novel features of the present
invention will become apparent from the following description
thereof.
Some of the compounds found in the human body can be
electrodeposited in a manner similar to the electrodeposition of
conventional organic chemicals. For instance, finely divided bone,
contained in an organic matrix, can be electrodeposited on various
metallic surfaces. The organic matrix enables the transference of
bone from the electrolytic medium to the electrode. If it were
possible to develop a charge, either cationic or anionic, on virgin
bone material, the use of an organic matrix would not be necessary.
One commercially available organic matrix or binder, Avitene, is a
microcrystalline collagen which is a water insoluble partial acid
salt of edible, bovine collagen. Gels produced from it contain a
large percentage of particles under one micron in any dimension.
The polypeptide collagen morphology and high molecular weight are
largely retained in the sub-micron micro-crystals which contain the
highly polar groups, NH, NH.sub.2 and OH.
Avitene forms translucent, viscosity-time stable,
thixotropic-pseudoplastic gels. High shear is necessary to produce
gels. The Waring Blendor and Cowles Dissolver are suitable for low
concentrations and sigma blade mixers for high concentrations.
Maximum viscosity is obtained at pH 3.0-3.4 At low pH (.about.2.5),
hydrolysis and unwinding of the collagen helix occurs and viscosity
decreases; the rate and extent increase with time, temperature and
decreasing pH. Above pH 4, gel structure becomes imperfect and
collagen fibers begin to coagulate. Salts and ethanol or
isopropanol also coacervate gels. Avitene can be made to gel a wide
variety of hydrophilic materials including methanol, glycerin,
formamide, dimethylsulfoxide, and ethanol or isopropanol/H.sub.2 O
solutions up to .about.40% alcohol/60% H.sub.2 O, by weight.
Avitene gels of the required concentration have been prepared by
attriting fibers in the desired medium for 15-30 minutes in a
Waring Blendor (Model 1003) using a lab-scale quantity of 400 grams
of Avitene. The concentration should not vary more than .+-. 0.01%
for reasonable reproducibility.
In performing the process of the present invention, the Avitene
fibers were allowed to soak for 5minutes in the medium and
thereafter were attrited for 2 minutes at a Powerstate (Type 116,
110 volts, Superior Electric Company,) setting of 20, and for 15
minutes minimum at a setting of 60-110 (depending on viscosity) to
maintain a controllable vortex. These conditions were applicable to
systems having viscosities up to 12,000-16,000 centipoises at room
temperature.
During attrition, gel temperature was maintained at
.about.25.degree.C by surrounding the jar with a plastic bag
partially filled with dry ice, and by reducing or completely
stopping agitation when necessary. Sides of the jar were policed at
intervals with a rubber spatula to insure thorough attrition. The
resultant gel was filtered through a fine, sintered glass filter to
remove larger, undispersed fibrils and particle aggregates.
The gel was returned to the Waring Blendor and a varying amount of
fine, powdered bone was added. After further agitation, a
suspension of finely divided bone, contained in a gel matrix of
Avitene, was obtained. The gel proved to be an excellent suspending
agent for the finely divided bone.
Initial investigations of several systems at either constant
voltage or constant current were carried out in an electrolytic
apparatus which consisted of a 500 ml Pyrex glass reaction kettle
with cover. Appropriate metal electrodes 2 .times. 1 0.02 inches
were attached by means of a stainless steel clip to 1/4 inch
stainless steel bars enclosed in glass tubing. Teflon rings were
used to seal the steel rods from the glass tubing. 300 ml of
solution was utilized and the anode to cathode separation was one
inch. A variable d.c. voltage was applied between the metal
electrodes, and the effects of the applied voltage on various
aqueous Avitene solutions was observed, recorded and are presented
in Table 1.
TABLE 1
__________________________________________________________________________
EFFECT OF APPLIED VOLTAGE ON VARIOUS AQUEOUS AVITENE
SOLUTIONS.sup.1 Approximate Weight of Applied Deposition Drying of
Coating Avitene Voltage Time Coated Thickness g V secs. Cathode
Cathode mils. Adhesion
__________________________________________________________________________
0.75 20 60 Al oven.sup.2 1 good 0.75 40 60 Al oven.sup.2 2 good
0.75 50 60 steel oven.sup.2 2 good 0.75 100 60 Al oven.sup.2 4 good
0.75 100 120 Al oven.sup.2 10 poor 0.75 100 120 steel air.sup.3 10
poor 1.5 50 60 Al oven.sup.2 3 good 1.5 50 60 steel oven.sup.2 3
good 1.5 100 60 Al oven.sup.2 5 fair 1.5 100 120 steel oven.sup.2 8
poor 3.0 50 60 Al oven.sup.2 6 poor 3.0 50 60 steel air.sup.3 6
poor 3.0 100 60 Al oven.sup.2 10 poor 3.0 100 120 steel oven.sup.2
15 very poor
__________________________________________________________________________
.sup.1 Each solution contained 400g of water, adjusted to pH 2.8 by
addition of dilute hydrochloric acid .sup.2 Oven baked at
70.degree.C for six hours .sup.3 Air dried for 48 hours
The systems were investigated at constant voltage, i.e. current
decreasing with electrodeposition time, or constant current, i.e.
voltage increasing with time. The following parameters were
investigated in the Avitene/bone electrodeposition:
(1) applied voltage, (2) electrode substrate, (3) nature of
solvent, (4) gel concentration, (5) bone concentration, (6)
electrodeposition time, and (7) air-drying or oven-drying (at
70.degree.C) of coated substrate.
In the first series of experiments, aqueous Avitene solutions,
suitably adjusted to pH 2.8 by the addition of dilute hydrochloric
acid, were subject to different applied potentials. Such a series
is shown in Table 1, supra. Three different Avitene concentrations
were used, and the applied voltage was varied between 20 and 100
volts. It was found that good adhesion to aluminum or stainless
steel substrates (cathodes) was achieved when the total coating
thickness was 4 mils or less. Thicknesses greater than 4 mils
resulted in very poor adhesion to the metallic substrate. Of the
concentrations investigated, it appeared that a concentration of
1.5g Avitene/400g water gave suitable coatings of .about.3 mils
when a potential of 50 volts was applied for 1 minute; very good
adhesion to the cathode was achieved.
In a second series of experiments, four separate solvents were used
and the results are shown in Table 2.
TABLE 2
__________________________________________________________________________
EFFECT OF VARIOUS SOLVENTS ON THE ELECTRODEPOSITION OF AVITENE
COLLAGEN Approximate Applied Deposition Drying of Coating Solvent
Voltage Time Coated Thickness Type.sup.1 V secs. Cathode Cathode
mils. Adhesion
__________________________________________________________________________
water 50 60 steel oven.sup.2 3 good water 50 60 Al oven.sup.2 3
good water 100 120 Al oven.sup.2 8 poor DMSO.sup.4 50 60 steel
oven.sup.2 <1 -- DMSO.sup.4 50 120 steel oven.sup.2 <1 --
DMSO.sup.4 100 240 Al oven.sup.2 1 poor DMSO.sup.4 200 300 steel
oven.sup.2 2 very poor a)DMSO.sup.4 100 300 steel oven.sup.2 2 poor
ethanol 50 60 steel oven.sup.2 -- -- ethanol 50 120 Al oven.sup.2
-- -- ethanol 200 300 Al oven.sup.2 -- -- Glycerin/ H.sub.2 O.sup.5
50 30 Al oven.sup.2 2 very good Glycerin/ H.sub.2 O.sup.5 100 60
steel oven.sup.2 5 very good Glycerin/ H.sub.2 O.sup.5 100 60 steel
air.sup.3 5 very good
__________________________________________________________________________
.sup.1 The solvent was adjusted to pH 2.8 by addition of dilute
hydrochloric acid. Weight of solvent was 400g, and weight of
Avitene was 1.5g for all samples except (a) which was 3.0g. .sup.2
Oven baked at 70.degree.C for six hours .sup.3 Air dried for 48
hours .sup.4 Dimethylsulfoxide .sup.5 (1:1, by weight)
From Table 2 it can be seen that Avitene/dimethylsulfoxide produced
solutions which have very poor electrocoating properties; solution
conductance was low and adhesion to the electrode was very poor.
Ethanol produced solutions possessing no electrocoating properties.
Aqueous solutions gave rise to reasonable electrocoating
properties. The best results were achieved utilizing a solvent
mixture of water/glycerin (50/50, by weight). This system had
excellent electrocoating properties and the resulting coatings have
the best overall adhesion to the metallic substrate. Coatings
having thickness of .about.5 mils were obtained in the latter
system by applying a potential difference of 100 volts for 60
seconds.
In a third series of experiments, finely divided bone was added to
the optimized Avitene/glycerin/water system prior to
electrodeposition. The results are shown in Table 3.
TABLE 3
__________________________________________________________________________
PARAMETERS INVESTIGATED IN THE BONE AVITENE/GLYCERIN SYSTEM.sup.1
Approx..sup.4 Weight of Weight of Applied Deposition Drying of
Coating Avitene Bone Voltage Time Coated Thickness g g V secs.
Cathode mils. Adhesion
__________________________________________________________________________
1.5 1.5 50 20 oven.sup.2 <1 -- 1.5 1.5 50 60 oven.sup.2 1 good
1.5 1.5 50 120 oven.sup.2 3 good 1.5 1.5 50 120 air.sup.3 3 poor
1.5 3.0 50 60 oven.sup.2 2 good 1.5 3.0 100 60 oven.sup.2 3 good
1.5 3.0 100 120 oven.sup.2 5 good 1.5 5.0 100 60 oven.sup.2 3 poor
1.5 5.0 100 60 air.sup.3 3 poor 1.5 5.0 100 120 oven.sup.2 5 poor
1.5 7.0 100 60 oven.sup.2 7 very poor 1.5 7.0 100 120 oven.sup.2
>10 very poor 1.5 7.0 100 120 air.sup.3 >10 very poor
__________________________________________________________________________
.sup.1 Solvent was a 400g solution of glycerin/H.sub.2 O (1:1, by
weight) adjusted to pH 2.8 by addition of dilute hydrochloric acid
.sup.2 The coated cathode was oven baked at 70.degree.C for six
hours .sup.3 Air dried for 48 hours .sup.4 Stainless steel
substrate was used in each electrodeposition
Four different bone concentrations were investigated. Under the
influence of the electric field, bone particles were transported
within the organic matrix of the cathode and deposited at this
electrode. A bone concentration of .ltoreq.2 parts bone to 1 part
of Avitene produced cathode coatings which had good adhesion to the
stainless steel substrate. When the concentration exceeded 2 parts
bone to 1 part Avitene, thicker coatings were obtained, i.e. for
equivalent applied voltage and electrodeposition time, but these
had extremely poor adhesion properties. The best coatings for
adhesion and thickness were achieved utilizing a solution comprised
of water/glycerin/Avitene/bone (200/200 1.5/3.0, by weight).
The present invention thus teaches a process by which bone and
collagen are simultaneously deposited by electrochemical deposition
onto an orthopedic implant to enhance bone repair rates in bone
bridge operations. A coating is deposited through a combination of
electrophoresis, electrocoagulation, electroosmosis and electrode
reactions. Of these, electrophoresis, which involves the movement
of charged particles, or ions, dispersed or dissolved in a liquid
medium, toward an electrode under the influence of an electric
field is considered to be of greatest importance. Colloidal
particles carry a large number of unit charges on their surfaces,
and each of these particles is thought in the present process to be
surrounded by a cloud of counter-ions. The charge of these
particles gives rise to the electrokinetic or Zeta potential, which
is a measure of the electrokinetic charge that surrounds suspended
particulate matter. Because of this charge, there is a mutual
repulsion of these particles and it is this repulsion which is
believed to cause these dispersions to be stable. The charges on
the colloidal particles are probably due to a combination of
absorbed ions from the solutions, from absorbed surfactant groups,
and from the particle itself having ionized groups at the
liquid-particle interface. Mobility is affected by the viscosity of
the medium, the size, shape and concentration of particles, the pH,
and the concentration of electrolyte.
The electrodeposition process provides several advantages in the
forming of superior prostheses. One advantage, controlled thickness
of electrodeposition, permits a very accurate coating to be applied
to a prosthesis, whether the repair involves a joint and/or socket,
a bone bridge, etc. A controlled thickness reduces the finishing
required to produce a frictionless, freely movable joint. The
electrodeposition process also provides for the uniform coverage of
irregularly shaped substrates. Because of electrodissolution of the
metallic electrode during electrodeposition, improved adhesion
properties are realized since the foreign substance is removed.
The electrodeposition process also permits the simultaneous
deposition of bone and collagen on an orthopedic implant. This
provides for a uniform dispersion of bone and collagen so that when
the metallic substrate is removed new bone formation in the damage
area is accelerated. The collagen, which is evenly dispersed within
the bone implant, promotes healing in connection with the bone
portion remaining in the body because of the common fibrous protein
in the collagen. Since this fibrous protein is found in connective
tissue, bone and cartilage in the body, the body processes do not
reject but rather enhance repair of the bone damage. The presence
of collagen also increases the rate of normal repair thereby
providing for a greater chance of success in bone bridge and other
bone operations. The process of the invention is also rapid in
relation to normal body processes or other forms of bone repair
such as pins, clamps, etc. The process also is exceedingly
economical since all the compounds used therein are readily
available and no complex equipment is required to make the
necessary substrates or form the electro-chemical deposition
thereon.
Obviously many modifications and variations of the present
invention are possible in the light of the above teachings.
* * * * *