U.S. patent application number 12/897498 was filed with the patent office on 2011-04-21 for implants and methdos for manufacturing same.
This patent application is currently assigned to ALLERGAN, INC.. Invention is credited to Alexei Goraltchouk, Thomas E. Powell, Dennis E. VanEpps.
Application Number | 20110093069 12/897498 |
Document ID | / |
Family ID | 43567536 |
Filed Date | 2011-04-21 |
United States Patent
Application |
20110093069 |
Kind Code |
A1 |
Goraltchouk; Alexei ; et
al. |
April 21, 2011 |
IMPLANTS AND METHDOS FOR MANUFACTURING SAME
Abstract
Implantable prosthesis, components of prosthesis, and methods of
making same are provided. The methods generally include the steps
of providing an implant shell, applying a curable fluid composition
to the shell to form a coating thereon and applying a particulate
component to the composition. The composition is a mixture, for
example, an emulsion, containing a silicone-based elastomer
dispersion and droplets of a suspended leachable agent. After the
elastomer is stabilized and cured, the particulate component and
leachable agent are removed, resulting in an implantable member
having a porous, open-cell surface texture designed to be effective
in reducing incidence of capsular formation or contraction.
Inventors: |
Goraltchouk; Alexei; (Santa
Barbara, CA) ; VanEpps; Dennis E.; (Goleta, CA)
; Powell; Thomas E.; (Santa Barbara, CA) |
Assignee: |
ALLERGAN, INC.
Irvine
CA
|
Family ID: |
43567536 |
Appl. No.: |
12/897498 |
Filed: |
October 4, 2010 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
61252330 |
Oct 16, 2009 |
|
|
|
Current U.S.
Class: |
623/8 |
Current CPC
Class: |
B05D 3/107 20130101;
A61L 27/30 20130101; A61L 2400/18 20130101; A61L 27/56 20130101;
A61F 2/12 20130101 |
Class at
Publication: |
623/8 |
International
Class: |
A61F 2/12 20060101
A61F002/12 |
Claims
1. An implantable member having an external surface at least a
portion of which is an open-cell porous structure, the member made
by the method comprising the steps of: (a) providing an implantable
shell; (b) applying a curable fluid composition to the shell, the
composition comprising a mixture containing an elastomer component,
a leachable agent and a solvent component; (c) applying a layer of
particles to the composition; (d) allowing the composition to
stabilize; and (e) removing the particles and the leachable agent
from the stabilized composition to form a composite material having
an external surface at least a portion of which is an open-cell
porous structure.
2. The member of claim 1 wherein the implantable shell is a shell
for a breast implant.
3. The member of claim 1 wherein the leachable agent is a water
soluble polymer.
4. The member of claim 1 wherein the leachable agent is an agent
selected from the group of agents consisting of polyvinyl alcohol,
polyethylene glycol, polyacrylic acid; polymethacrylate,
poly-lactide, polyglycolide, polycaprolactone, polydioxanone,
derivatives thereof, blends thereof, copolymers thereof,
terpolymers thereof, and combinations thereof.
5. The member of claim 1 wherein the solvent component includes a
solvent selected from the group consisting of xylene, pentane,
hexane, dichloromethane (DCM), dimethyl sulfoxide, dioxane, NMP,
DMAc, and combinations thereof.
6. The member of claim 1 wherein the mixture is an emulsion.
7. The member of claim 1 wherein the particles comprise a material
selected from the group of materials consisting of sodium chloride,
barium sulfate, potassium nitrate, sodium carbonate.
8. The member of claim 1 wherein the particles are substantially
round.
9. The member of claim 1 wherein the leachable agent is in the form
of droplets having diameters in a range of between about 50 microns
to about 400 microns.
10. The member of claim 9 wherein the particles have an average
particle size in a range of between about 100 microns to about 900
microns.
11. The member of claim 1 wherein the particles have an average
particle size in a range of between about 100 microns to about 900
microns.
12. The member of claim 1 further comprising the step of repeating
steps (b) and (c) prior to the step of removing, to form a layered
structure.
13. The member of claim 1 wherein the step of removing comprises
contacting the stabilized composition with a solvent for the
particles and the leachable agent.
14. An implantable composite member having an external surface at
least a portion of which is an open-cell porous structure, the
member made by the method comprising the steps of: (a) providing an
implantable shell; (b) applying a first layer of a curable fluid
composition to the shell, the composition comprising a mixture
containing an elastomer component, a leachable agent and a solvent
component; (c) applying a first layer of particles to the
composition; (d) applying a second layer of the composition to the
first layer of particles; (e) applying a second layer of particles
to the second layer of the composition; (f) allowing the
composition to stabilize; and (g) removing the particles and the
leachable agent from the stabilized composition to form a composite
material having an external surface at least a portion of which is
an open-cell porous structure.
15. The member of claim 14 wherein the first layer of particles
comprises relatively small particles and the second layer of
particles comprises relatively large particles.
16. An article suitable for use in as a laminate for an implant,
the article comprising: a flexible sheet made by the process of:
(a) applying a particulate component and a curable fluid
composition to a mold surface, the fluid composition comprising a
mixture containing an elastomer component, a leachable agent and a
solvent component; (b) allowing the fluid composition component to
stabilize; and (c) removing at least one of the particulate
component and the leachable agent from the stabilized composition
to form a sheet having an external surface at least a portion of
which is an open-cell porous structure; and (d) removing the sheet
from the mold surface.
17. An article comprising: a sheet suitable for use as a laminate
on an implantable object to enhance tissue adhesion or ingrowth
when the implantable object is implanted in a patient; the sheet
made by a process comprising the steps of: applying a
fluid/particulate mixture to a substrate or mold surface, the
fluid/particulate mixture comprising a particulate component and a
curable fluid component, the curable fluid component containing an
elastomer component, a leachable agent and a solvent component;
allowing the fluid/particulate mixture to stabilize; and removing
the sheet from the substrate or mold surface.
18. The article of claim 17 further comprising the step of removing
at least one of the particulate component and the leachable agent
from the stabilized fluid/particulate mixture to form a porous
sheet after the step of allowing the fluid/particulate mixture to
stabilize.
19. The article of claim 18 wherein the step of removing at least
one of the particulate component and leachable agent is performed
prior to the step of removing the sheet from the substrate of mold
surface.
20. The article of claim 17 wherein the sheet is a layered sheet
and the process further comprises the step of repeating the
applying step prior to the step of removing the sheet from the
substrate or mold surface.
Description
[0001] This application claims priority to U.S. Provisional Patent
Application No. 61/252,330, filed on Oct. 16, 2009, the entire
disclosure of which is incorporated herein by this specific
reference.
BACKGROUND
[0002] The present invention generally relates to soft tissue
implants and more specifically relates to soft tissue implants
designed to enhance fixation in the body and/or alter or reduce
capsular formation.
[0003] Soft tissue implants, particularly mammary prostheses, are
plagued by problems of capsular formation and contracture. Soon
after an implant is placed into the body, an inflammatory response
begins to deposit a fibrous capsule around the implant. In most
cases, particularly for relatively large and smooth implants, the
capsule is comprised of highly organized or aligned collagen
fibers. As the capsule matures, certain events may trigger the
differentiation of fibroblasts to a contractile phenotype
(myofibroblasts). In this or similar scenarios, and if the collagen
fibers are aligned, capsular contracture may ensue.
[0004] Capsular contracture can be debilitating to the patient
because of discomfort or even pain caused thereby, can diminish the
efficacy of the aesthetic results in both the look and feel of the
implant, and can sometimes damage the implant itself. Problems with
capsular formation and contracture occur in many implant types such
as pacemakers, dura matter substitutes, implantable cardiac
defibrillators, pacemaker leads, hernia repair meshes as well as
breast and other esthetic implants.
[0005] It has been established in the literature that surface
texturing of implants often helps to reduce the incidence of
capsular contracture when compared to smooth surface implants.
Furthermore there is increasing evidence regarding the ability of
foam covered implants, for example, polyurethane foam coated
implants, to reduce contracture rates. However, polyurethane foam
coatings are biodegradable and lose their efficacy once the
polyurethane degrades. Further, it can be appreciated that
degradation of polyurethane foam into the body is undesirable and
potentially unhealthy.
[0006] The present invention addresses at least some of these
drawbacks of conventional implants.
SUMMARY OF THE INVENTION
[0007] The present invention provides implantable members and
methods for manufacturing implantable members, for example,
prostheses, for example, mammary prostheses, as well as components
of prostheses, for example, elastomeric shells, which serve as
components of mammary prostheses. The invention further provides
coverings, for example, laminates for applying to surfaces of
implantable devices. The implantable members have surfaces which
may enhance fixation and/or alter or reduce capsular formation. In
one aspect of the invention, the textured surfaces are defined by a
network of interconnected pores and channels which encourages
tissue ingrowth and discourages organization of the collagen
capsule. Generally, the pores have, on average, more than two
interconnections assuming that the average number of
interconnections per pore does not vary significantly.
[0008] The method generally comprises the steps of providing an
implantable member, for example an implant shell, for example, a
conventional smooth silicone-based implant shell, and applying a
curable fluid composition to the shell to form a coating thereon.
In one embodiment, the composition comprises a silicone-based
mixture including a solvent, and a pore-forming material, for
example, a leachable agent, dispersed therein. The composition is
allowed to stabilize on the shell, for example, by allowing some of
the solvent to evaporate out of the composition or allowing a
chemical reaction to occur inducing precipitation of the soluble
components. Alternatively, stabilization can be achieved during
crosslinking of polymerization of the silicone, precipitation of
the silicone or pore-forming material of a combination of the above
alone or in conjunction with solvent evaporation.
[0009] Next, a particulate component, hereinafter sometimes simply
referred to as "particles" or a "particle coating", is applied to
the composition coating while the composition coating is less than
entirely cured, or at least has a stickiness or tackiness capable
of retaining the particulate coating.
[0010] In some embodiments, the steps of applying a curable fluid
composition and applying a particle coating are then repeated, for
example, one or more times, for example, three, five or even up to
20 times, until a final coating is applied. The final coating may
be a particle coating or a composition coating.
[0011] After the final coating of particles or fluid composition is
applied to the shell, the coated shell is then subjected to
suitable curing conditions to solidify the composition with the
particles embedded therein.
[0012] In one embodiment, the particulate coating itself is used to
stabilize the coating composition, for example, by absorbing some
or all of the solvent, increasing the rate of polymerization of
crosslinking of the silicone, promoting precipitation of the
silicone or porogen, or a combination of one or more of the
above.
[0013] Once solidified, the leachable agent contained in the
composition and the particles embedded therein are then removed
from the coating thereby revealing a network of interconnected
pores (the structure may include both relatively large pores and
relatively smaller pores, for example, micropores) within the cured
elastomer. The surface topography created by the processes
described herein, when used as a part of an implant at the
tissue/implant interface, may be highly effective in altering
capsular formation so as to achieve a more preferred morphology, or
in reducing or preventing capsular contracture, relative to
conventional surface topographies.
[0014] Removal of the particles and leachable agent may be
accomplished by any suitable means effective to remove these
materials from the surrounding elastomer "matrix", and create the
desirable surface topography.
[0015] For example, the particles and/or leachable agent(s) may be
extracted by exposing the coating to one or more suitable mediums
capable of dissolving, extracting or otherwise removing the
particles and/or leachable agent while leaving the cured elastomer
matrix generally intact.
[0016] Generally, the particles, which are typically larger in size
than the dispersed leachable agent, serve to create cavities or
pores in the cured elastomer while the dispersed leachable agent
serves to create microcavities or micropores which serve as
interconnections between the pores. This network of interconnected
pores and micropores facilitates tissue ingrowth, encourages better
fixation of the implant in the patient, and discourages
organization of the fibrous capsule, which may help reduce or
prevent capsule formation and contraction.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] The present invention may be more clearly understood and the
aspects and advantages thereof more clearly appreciated with
reference to the following detailed description and accompanying
drawings of which:
[0018] FIGS. 1A-1C represents suitable process steps in a method
for manufacturing an elastomeric shell in accordance with an
embodiment of the invention;
[0019] FIGS. 2-6 are cross-sectional views of components of the
shell during various steps of the process for making the shell
shown in FIGS. 1A-1C.
[0020] FIG. 7 is a simplified flow chart showing steps in a method
for manufacturing an implant shell in accordance with an embodiment
of the invention.
DETAILED DESCRIPTION
[0021] Accordingly, implantable composite members and methods for
manufacturing such implantable composite members are provided.
[0022] In one aspect of the invention, the present invention
provides an implantable composite member, hereinafter, typically
referred to as an "implant", having a surface that renders the
implant effective in reducing the occurrence or severity of capsule
formation when the implant is placed in the body. In a specific
exemplary embodiment that will now be described, the implant is a
fillable mammary prosthesis useful in breast reconstruction or
breast augmentation. It should be appreciated, however, that the
present invention is not limited to mammary prostheses, but is
useful in many situations in which an implant is intended to be
permanently or temporarily placed in the body and which capsule
formation or contraction is to be avoided or impaired.
[0023] First, in a method of the invention, an implant member is
provided. The implant member may be a fillable, elastomeric implant
shell having a configuration of a breast prosthesis. Such shells
are intended to be filled, typically, with saline or silicone gel
before or after implantation in the breast.
[0024] Generally, manufacture of such shells is commonly
accomplished by applying a liquid dispersion, for example, a
silicone elastomer dispersion, to a mandrel having a desired form.
The dispersion generally contains a silicone elastomer and a
solvent. The silicone elastomer may be polydimethylsiloxane,
polydiphenyl-siloxane or some combination of these two materials.
Typical solvents include xylene, trichloromethane, heptane, hexane,
and toluene.
[0025] The silicone dispersion forms an elastomeric coating on the
mandrel. The coating is cured and the solvent evaporates therefrom.
This procedure may be repeated a number of times in order to obtain
an implant shell having a desired thickness. This shell may be used
as base component for many of the implants of the present
invention.
[0026] In accordance with one aspect of the invention, an
implantable member having a desired surface topography is provided.
The method comprises the steps of applying a curable fluid
composition to a substrate, for example, a surface of an implant
shell described above, applying a particulate material to the
composition, and in some instances, repeating these steps to
achieve layers, for example, alternating layers of composition and
particulates. The composition includes a leachable component to be
described elsewhere herein. The composition layers are allowed to
stabilize between subsequent applications.
[0027] Once the layering steps are completed, the composition is
subject to conditions to allow it to at least partially cure.
Curing process steps will depend on the materials used. One or more
process steps are performed to remove the particles of the particle
layer(s) and the leachable component from the elastomer.
[0028] The resulting implant has an external surface at least a
portion of which is an open-cell porous structure having a
topography or porosity that affects capsule formation and/or
adhesion of the implant when implanted in a patient.
[0029] The curable fluid composition may be in the form of an
emulsion, dispersion, solution, suspension or mixture containing an
elastomer component, a solvent component and a leachable
component.
[0030] The elastomer component may be an uncured silicone polymer,
for example, a silicone elastomer. For example, in some
embodiments, the elastomer component is a room temperature
vulcanizing (RTV) silicone elastomer. The elastomer component may
be polydimethyl siloxane, polydiphenyl siloxane or a combination of
these two. Possible silicone elastomer systems useful in the
present invention include, but are not limited to, oxime, platinum
or tin catalyst based systems. Alternatively, the elastomer
component may be a non-silicone based material.
[0031] The solvent component may be any suitable solvent or solvent
system, appropriate to the elastomer. Representative examples of
solvents include chloroform, acetone, water (buffered saline),
dimethyl sulfoxide (DMSO), propylene glycol methyl ether (PM),
isopropyl alcohol (IPA), n-propyl alcohol, methanol, ethanol,
tetrahydrofuran (THF), dimethylformamide (DMF), dimethyl acetamide
(DMAC), N-Methylpyrrolidone (NMP), benzene, toluene, xylene,
hexane, cyclohexane, heptane, octane, pentane, nonane, decane,
decalin, ethyl acetate, butyl acetate, isobutyl acetate, isopropyl
acetate, butanol, diacetone alcohol, benzyl alcohol, 2-butanone,
cyclohexanone, dioxane, methylene chloride, carbon tetrachloride,
tetrachloroethylene, tetrachloro ethane, chlorobenzene,
1,1,1-trichloroethane, formamide, hexafluoroisopropanol,
1,1,1-trifluoroethanol, and hexamethyl phosphoramide and
combinations thereof. In one embodiment, the solvent is selected
from the group of solvents consisting of xylene, pentane, hexane,
heptane, dichloromethane, trichloromethane, toluene, dimethyl
sulfoxide, dioxane, NMP, DMAC, and combinations thereof. The
solvent component may comprise one or more different solvents. For
example, the solvent component may comprise between one and twenty
different solvents. Generally, the solvent may comprise any
suitable protic or aprotic solvent, mixture or solution
thereof.
[0032] The leachable component is a leachable material/agent in the
form of any suitable solid particulates, semi-solids, composites,
gels, for example, hydrogels, liquid droplets, etc. The leachable
agent may comprise any suitable polymer, ceramic, metal, composite
or combination thereof that can be dissolved or otherwise removed
by suitable means from the cured formulation. In some embodiments,
the composition comprises one or more different leachable agents.
For example, the composition may comprise between one and twenty
different types of leachable agents.
[0033] The elastomer component can be present in the composition in
a range of about 1% to about 99% of volume as part of the total
dissolved solids and the leachable agent can be in the range of
about 1% to about 99% of volume as part of the total dissolved
solids. In a specific embodiment of the invention, the composition
includes up to 96% leachable phase. In some embodiments, the
elastomer component is present in the composition in a range of
about 5% to about 80% and the leachable agent is present in the
composition in a range of about 20% to about 95% of total dissolved
solids. Generally, the total dissolved solids in the composition
can range from about 1% to about 50% by weight in solution.
[0034] The ratio of leachable phase to matrix phase in the
composition generally affects the porosity of the final cured
composition. For example, a greater percentage of leachable
component in the composition will produce a composition layer
having greater interconnections between pores.
[0035] In an exemplary embodiment, the curable fluid composition is
in the form of an emulsion, and the leachable agent is present in a
concentration of up to about 50% concentration by volume of the
emulsion. In some embodiments, the composition comprises a
microphase separation containing an elastomer matrix phase and
droplets of leachable material in suspended phase, the droplets
being about 0.01 .mu.m to about 10,000 .mu.m in diameter, for
example, about 1 .mu.m to about 5,000 .mu.m in diameter, for
example, about 50 .mu.m to about 400 .mu.m in diameter. After the
leachable agent has been leached from the elastomer, voids left
behind by the leachable agent will serve as interconnections
between voids left by the removed particles.
[0036] The leachable agent may be, for example, any material that
can be dispersed through the elastomer dispersion (elastomer
component/solvent system) and can be removed therefrom once the
elastomer component is cured. The leachable agent may be an agent
that can be removed from the cured elastomer, for example, by
leaching, evaporation, sublimation, dissolution, etc. In an
exemplary embodiment, the leachable agent is a water soluble
material dispersed throughout the elastomer dispersion.
[0037] Typical leachable agent in accordance with the invention may
comprise, for example, polyethylene glycol (PEG) (also known as
polyoxyethylene), polyalkylene oxides including polyethylene oxide
and polyethylene oxide/polypropylene oxide copolymers (also known
as poloxamers), polyhydroxyethylmethacrylate, polyvinylpyrrolidone,
polyacrylamide and its copolymers, polylactides, polyglycolides,
polyanhydrides, polyorthoesters and their copolymers, proteins
including albumin, peptides, liposomes, cationic lipids, ionic or
nonionic detergents, salts including potassium chloride, sodium
chloride and calcium chloride; sugars including galactose, glucose
and sucrose; polysaccharides including soluble celluloses, heparin,
cyclodextrins and dextran; and any combination thereof.
[0038] In some embodiments, the leachable agent is an agent
selected from the group of agents consisting of polyvinlyl alcohol,
polyethylene glycol, polyacrylic acid, polymethacrylate,
poly-lactide, polyglycolide, polycaprolactone, polydioxanone; and
derivatives, blends, copolymers, terpolymers, and combinations
thereof.
[0039] In some embodiments, the leachable agent is in the form of
droplets of leachable material having diameters in a range of
between about 0.01 micron to about 10,000 microns. For example, the
leachable agent may be in the form of droplets having diameters in
a range of between about 1 micron to about 5,000 microns, for
example, in a range of between about 50 microns to about 400
microns.
[0040] The particulates of the particle layer comprise any suitable
particles which may be removed from the cured elastomer, leaving
cavities where the particles had been.
[0041] For example, the particles may comprise particles that can
be removed from the elastomer by at least one of mechanical
abrasion, leaching, evaporation, sublimation, dissolution etc.
[0042] In an exemplary embodiment, the particles are a solid, water
soluble material. For example, the particles may be material
selected from the group of materials consisting of sodium chloride,
barium sulfate, potassium nitrate and sodium carbonate.
[0043] In addition, the particles may have dimensions and shapes as
desired to bring about a resulting topography. For example, the
particles may be substantially round or spherical, multifaceted,
angular, or cubic or a combination thereof. The particles may have
an average particle size in a range of between about 0.01 micron to
about 10,000 microns, for example, in a range of between about 10
microns to about 6,000 microns, for example, in a range of between
about 100 microns to about 900 microns.
[0044] In some embodiments, the size of the particles is
approximately proportional to the thickness of the composition
coating on which they are deposited, or the thickness of adjacent
interconnecting composition coatings in a multilayered embodiment.
For example, particles with an average size of about 500 micron
could be used in conjunction with a composition layer having a
thickness of about 100 microns to about 500 microns. For particles
with an average size of about 300 microns, a composition layer of
about 50 microns to about 400 microns could be used.
[0045] FIGS. 1A-1C illustrate an exemplary process for making an
implant in accordance with an embodiment of the invention. Step one
is illustrated in 1A. In FIG. 1A, a flexible, elastomeric
implantable member 12 is depicted. The partial cross sectional view
11 of the elastomeric implant member 12 is shown in FIG. 1A as well
as FIG. 2. The implantable member 12 may be a cured implant shell,
such as a conventional, relatively smooth-surfaced, silicone-based
elastomeric implant shell, for example, a shell intended to be
filled with silicone gel or saline and used as a breast
prosthesis.
[0046] A curable fluid composition 14, as described elsewhere
herein, is applied to the outer surface of the shell 12. FIG. 3
shows a partial cross sectional view of a shell 12 having a
composition coating 10. This may be accomplished by dipping the
shell (as shown by shaded line 13), while the shell is fixed to a
mandrel (not shown) into a solution bath containing the curable
fluid composition 14 (FIG. 1A). The composition 14 comprises a
silicone-based mixture including a solvent, and a leachable agent,
as described elsewhere herein. The step of applying the composition
14 to the shell 12 may be accomplished by any suitable means of
application, such as dipping and spraying.
[0047] Next, the composition coating is allowed to stabilize on the
shell 12. For example, the shell 12 can be held in a stable
position until the composition coating no longer flows freely. This
occurs as some of the solvent evaporates from the coating, raising
its viscosity. It can be appreciated that the step of allowing the
composition to stabilize may be accomplished by various means, for
example, by allowing some of the solvent to evaporate out of the
composition or allowing a chemical reaction to occur, inducing
precipitation of the soluble components. Alternatively,
stabilization can be achieved during crosslinking of polymerization
of the silicone, or precipitation of the silicone or pore-forming
material. Also, a combination of the above-mentioned methods may be
used for stabilization of the composition coating.
[0048] Once the composition 14 has stabilized on the shell 12, the
second step is to immerse (see shaded line 15) the shell 12 in a
particle bath 16 to apply particles to the composition coating on
the shell 12 (FIG. 1B). The particles 18 applied to a
composition-coated shell 12 is depicted in FIG. 1B. FIG. 4 shows a
partial cross sectional view of a shell 12 with a composition coat
10 and particles 18. Application of the particle coating onto the
shell 12, is performed while the composition coating on the shell
12 is still tacky and able to retain the particles. Stabilizing the
composition prior to particle application may be accomplished by
allowing at least some of the solvent in the composition to
evaporate out of the composition until the composition is stable
and tacky but not fully cured. Another method, in accordance with
one aspect of the invention, for stabilizing the composition is
provided in the Example below.
[0049] Steps one and two can be repeated before the leaching step
is carried out, as indicated by shaded line 17. The steps of
applying a curable fluid composition and applying a particle
coating can be repeated, for example, one or more times, for
example, three, five or even up to 20 times, until a final coating
is applied. The final coating may be a particle or a composition
coating.
[0050] After the final coating of particles or fluid composition is
applied to the shell, the coated shell is then subjected to
suitable curing conditions to solidify the composition with the
particles embedded therein.
[0051] In the leaching step 19 (FIG. 1C), which takes place after
the solidification step described above, the embedded particles and
leachable agent in the composition coating are immersed in a
leaching bath 20 and removed. After the removal of the particles,
what remains is a network of interconnected pores 21 (the structure
may include both relatively large pores and relatively smaller
pores, for example, micropores) on the shell.
[0052] Also see FIG. 7 for a flow chart of the process described
herein.
Example 1
[0053] A mixture of about 7.5 wt. % PVA 2000 in water and about 40
wt. % acetoxy RTV silicone in xylene in a 3:1 volumetric ratio is
prepared and homogenized for 30 seconds. An acetyl mandrel is
placed into the mixture and coated uniformly as in a standard
dip-coating process for the manufacturing of breast implant shells.
The mandrel is then placed into a fluidized bed reactor with salt
granules until no more granules can be deposited on the mandrel
(about 5-10 seconds). This addition of salt particles tends to dry
and stabilize the mixture by absorbing some of the water, thereby
increasing the viscosity of the mixture. The coating is allowed to
stabilize further at either 90.degree. C. for about 15 minutes or
at room temperature for about 1/2 hour, or otherwise sufficiently
such that the next layer of composition may be applied. The
procedure is repeated 3-5 times to obtain a coating of desired
thickness.
[0054] Final curing may be performed at 165.degree. C. for 2 hours,
leaching with water or DCM for about 30 minutes for about 3 cycles
with each (with agitation), and drying in vacuum overnight.
[0055] In one embodiment, a material is added to the composition
before or after the composition has been applied to the shell, the
material being effective to increase the viscosity of the
composition, for example, by absorbing some of the solvent. When
the leachable agent is in water, for example, a salt can be added
in order to dry/stabilize the phase by absorbing the solvent. Other
materials that may be helpful in this regard include sugars and
other appropriate materials that can accelerate removal of solvent
from the composition.
[0056] Next, a particle coating is applied to the composition to
form the pores or cavities in the final elastomer foam structure.
Application of the particles may be accomplished by any suitable
means, for example, by sprinkling and pressing the particles into
the tacky composition coating, or by immersing the tacky, coated
shell in a bath of the particles. In the example shown, the
particles are applied by immersing the coated shell into a
fluidized bath 18 comprising a fluidization medium 19, for example,
air, and particulates, for example, salt particles.
[0057] In some embodiments, the steps of applying the curable fluid
composition and applying the particle coating are then repeated one
or more times, for example, from about 0.5 up to about 20 times,
for example, about 1 to about 10 times, for example, about 2 to
about 5 times.
[0058] In one aspect of the invention, the particle coatings
applied to the composition coatings may comprise coatings of
particles having relatively different dimensions, one layer from
the other. In other words, a first layer of particles may be
relatively fine particles and a second layer of particles may be
relatively coarse particles, or vice versa.
[0059] It is contemplated that in some embodiments,
interconnectivity between pores may be increased or controlled by
causing the particulates in the particle layer to fuse together.
For example, in the event that the particles are salt crystals,
application of moist heat may be effective increase
interconnectivity thereof. Alternatively or additionally, an
appropriate amount of a solvent for the particle material may be
applied in order to cause the particles to fuse together. Further
information which may be useful in appreciating this aspect of the
invention may be found in copending, commonly owned U.S.
Provisional Patent Application No. 61/177,955, filed on May 13,
2009 and entitled: IMPLANTS AND METHODS FOR MANUFACTURING SAME, the
entire disclosure of which is incorporated herein by this
reference.
[0060] For example, in one embodiment, the steps of applying
alternating particle and compositions coatings includes applying a
first layer of the curable fluid composition to the shell, applying
a first layer of particles, for example, relatively small
particles, to the composition, applying a second layer of the
composition to the first layer of particles, applying a second
layer of particles, for example, relatively larger particles, to
the second layer of the composition. FIG. 5 is a cross sectional
view of a shell showing alternating layers of compositions coatings
10 and particle coatings 18. In a specific embodiment, the first
layer of particles comprises particles having an average size in a
range of between about 30 microns to about 150 microns, and the
second layer of particles comprises particles having an average
size in a range of between about 100 microns to about 450 microns.
In yet other embodiments, the method further includes applying a
third layer of the composition to the second layer of particles,
and optionally, providing a third layer of particles, to the third
layer of composition. The third layer of particles may have an
average size in a range of between about 250 microns to about 750
microns.
[0061] The layered, coated shell is then subjected to suitable
curing conditions to solidify and further stabilize the composition
with the particles embedded therein.
[0062] Next, the particles and leachable agent are then removed
from the cured coating, thereby revealing a network of highly
interconnected pores within the cured elastomer. FIG. 6 shows the
partial cross sectional view of the shell 11 with a network of
interconnected pores 21 after the removal of the particles. The
step of removing the particles may comprise causing the particles
to dissolve or contacting the particles with an abrasive surface.
In the same step or in a different step, the leachable agent in the
composition layers are removed from the elastomer.
[0063] In some embodiments, a conventional gas foaming process is
used in addition to one or more of the presently described
processes of the invention. For example, prior to the steps of
applying the composition to the shell, the composition may be
aerated by passing a gas, for example, air, through the composition
to aerate the composition and create bubbles therein.
Advantageously, any surface skin that may begin to form on the
aerated composition coating would be opened up during extraction of
the leachable phase to reveal highly interconnected pores resulting
from the leachable materials, the particulates and the gas
bubbles.
[0064] Removal of the particles and leachable agents may be
accomplished by extracting these materials by exposing the layers
to one or more suitable mediums capable of dissolving the particles
and/or leachable agents. For example, the coated shell is dipped or
submerged in a leaching bath 19 (FIG. 1C). The leaching bath may
comprise water or an aqueous solution containing an agent capable
of dissolving, leaching or otherwise removing the leachable agent
and/or particles while leaving the cured elastomer substantially
intact.
[0065] In some embodiments, the particles which are typically
larger than the dispersed leachable agent, serve to create pores in
the cured elastomer and the dispersed leachable agent serves to
create micropores or interconnections between the relatively larger
pores.
[0066] The resulting open-cell structure is believed to facilitate
tissue ingrowth, improve fixation or adhesion of the implant and
discourages organization of the collagen capsule which forms about
the implant, which may help reduce capsular contraction.
[0067] In another aspect of the invention, an implantable composite
member is provided in which the composite member has an external
surface at least a portion of which is an open-cell porous
structure, the composite member being made by one of the processes
described herein.
[0068] In yet other embodiments of the invention, each of the first
and second layers of particles are made up of substantially
uniformly sized/shaped particles. In another aspect of the
invention, each of the first and second layers of particles are
made up of differently sized or shaped components.
[0069] After finishing the shell according to the steps described
above, the steps required to make a finished mammary prosthesis may
be conventional. First, any opening left by the mandrel support is
patched with uncured silicone elastomer sheeting. If the prosthesis
is to be filled with silicone gel, this gel is added and cured, the
filled prosthesis packaged, and the packaged prosthesis sterilized.
If the prosthesis is to be inflated with a saline solution, a valve
is assembled and installed, the prosthesis is post cured if
required, and the prosthesis is then cleaned, packaged and
sterilized. A combination silicone/saline mammary prosthesis can
also be made.
[0070] A method has been described for creating an outer layer
having an open-cell structure in a silicone elastomer member. More
specifically, the method can be applied to create a medical implant
with an external surface layer of silicone elastomer having an
open-cell structure, to create strips having a textured surface for
control of scar formation, or to improve a process for making
mammary prostheses. The product made by this method has also been
described and is expected to have great utility in reducing
capsular contraction, in preventing or controlling scar formation,
and in anchoring medical implants.
[0071] Scar tissue formation in the healing of a wound or surgical
incision is also a process involving the growth of fibrous tissue.
A visible scar results from this healing process because the
fibrous tissue is aligned in one direction. However, it is often
aesthetically desirable to prevent scar formation, especially in
certain types of plastic surgery. A member having an open-cell
structure surface made in accordance with the present invention can
be placed subcutaneously within a healing wound or incision to
prevent the fibrous tissue from aligning and thereby prevent or
reduce scar formation.
[0072] It is often important to anchor medical implants against
movement. Mammary prostheses are one example of implants that must
be anchored. Facial implants are another example of implants that
must be anchored. With facial implants it is particularly important
that they be anchored securely against movement because of their
prominent location. Providing such implants with an open-cell
structure surface made in accordance with the present invention is
a particularly advantageous way to ensure that they will be
anchored securely.
Example 2
[0073] A composition is prepared by mixing polyethylene glycol
monomethyl ether (2000 Da), which will serve as a leachable agent,
with a low viscosity silicone elastomer dispersion, for example,
(e.g. polydimethylsiloxane, polydiphenylsiloxane,
poly(dimethylsiloxane-co-diphenylsiloxane),
poly(dimethylsiloxane-ran-diphenylsiloxane), etc.), in an organic
solvent (e.g. xylene), and at about 5 to about 40 wt %, or in some
specific embodiments, 17, 25 and 35 wt % of acetoxy RTV silicone.
This composition is applied to the surface of an elastomeric shell
held on a mandrel or other mechanical support. The layer is allowed
to evaporate most of the solvent off.
[0074] A coating of sodium chloride crystals (about 250 .mu.m to
about 850 .mu.m size) are applied to the tacky composition layer by
submerging the coated shell into a fluidized bath of salt and air.
This forms a relatively uniformly distributed single layer particle
coating.
[0075] The elastomer is allowed to evaporate the solvent off and
subsequently cured at approximately 145.degree. C.
[0076] The coated shell is then submerged in an aqueous washing
medium at approximately 40.degree. C. and gently agitated to remove
the particles and leachable agent.
Example 3
[0077] The same process is performed as in Example, 1, except that
the composition is a mixture of 10 mL xylene, 10 mL DCM, 5 mL by
dry volume PEG 2000 and 5 mL by dry volume acetoxy RTV silicone
elastomer.
Example 4
[0078] The same process is performed as in Example 2, except that
the composition is a mixture of
5 mL water 1 mL xylene 0.5 mL by dry volume PVA 1500 0.2 mL by dry
volume RTV.
[0079] In another aspect of the invention, an article, for example
a thin, flexible sheet, useful as a laminate, is provided. More
specifically, the present invention provides a biocompatible sheet
suitable for use as a laminate on an implantable device or object,
in order to enhance tissue adhesion or ingrowth when the
implantable device or object is implanted in a patient. Thus, the
manufacture of the materials in accordance with the invention is
not limited to conventional dipping processes but may be made by
other suitable means, for example, through the lamination of a
sheet that is prepared by molding or casting. For example, it is
contemplated by the inventors that a sheet or laminate can be
prepared by casting the fluid material with all the components
present in various ratios (DCM, PEG)+(Xylene, RTV), and in some
instances, mixed and shaken with the particulate component, for
example, salt crystals added to the liquid. The particulate and
fluid mixture can be shaken or mixed and cast onto a substrate or
into a mold cavity. In some embodiments, the particulate component
comprises salt in a range of about 10% to about 99% of total
dissolved solids. In a more specific embodiment, the salt is
present at about 25% to about 60%. It can be appreciated that
different amounts and different particle sizes/shapes of salt will
produce laminates having different porosities. Once cured, the
laminate can be laminated, by any conventional means known in the
art, onto a medical device or implant or other object to be
implanted in a body, for example, any object or device which would
be improved by the addition of such a laminate on one or more
surfaces of the object or device. For example, the sheet may be
laminated to catheter cuffs for long term implantable catheters,
dura-matter substitutes or the like.
Example 5
[0080] A laminate for an implant is prepared as follows. A fluid
composition made up of 10 mL xylene, 10 mL DCM, 5 mL by dry volume
PEG 2000 and 5 mL by dry volume acetoxy RTV silicone elastomer is
mixed with 3.5 mL by volume salt particles. This mixture is shaken
together to ensure substantially uniform distribution of particles.
The mixture is cast molded by applying the mixture to a mold
surface to form a layer having a uniform thickness of between about
1 mm to about 5 mm. The layer is allowed stabilize and is cured at
about 120.degree. C. for a sufficient period of time. The cured
sheet is removed from the mold surface and is then contacted with a
gentle spray of pure water to remove all of the leachable
components and salt particles. The resulting, thin, flexible,
porous silicone foam sheet is then further processed and sterilized
and packaged for sale or storage for later use as a laminate on a
surface of an implantable device.
Example 6
[0081] The process of Example 5 is performed with the additional
steps of repeating, three times, the step of applying a fluid
composition/particulate mixture to the stabilized layer prior to
the step of curing. The final thin, flexible sheet is a
multilayered sheet and, in this example, has a thickness of greater
than about 5 mm.
Example 7
[0082] The process of Example 5 is performed, however the cured
stabilized sheet is not contacted with a spray of water to remove
the leachable agents and particulates before being packaged for
sale or storage. Instructions are provided with regard to: removing
the leachable agents and particulates, sterilization, and bonding
the sheet to a surface of a medical device.
Example 8
[0083] The process of Example 5 is performed to make two square
sheets of uncured foam, approximately 240 mm.times.240 mm. A layer
of silicone adhesive in DCM is applied, by spraying or brushing, to
one side of each of the sheets. The sheets are stretched uniformly
and positioned one on top of the other, adhesive side facing each
other, over a newly molded breast implant shell filled with
silicone or air. The foam sheets are joined together at the edge of
the implant and affixed by suitable clamps at the perimeter of the
implant. Twenty four hours later, the clamps are removed. Excess
foam is die-cut away from the implant by a press. The implant/foam
is exposed to 140.degree. C. for 2.5 hours for final
post-curing.
[0084] While this invention has been described with respect to
various specific examples and embodiments, it is to be understood
that the invention is not limited thereto and that it can be
variously practiced within the scope of the invention.
* * * * *