METHODS FOR CREATING FOAM-LIKE TEXTURE

[0001] This application is a divisional of U.S. patent application Ser. No. 13/297,120, filed Nov. 15, 2011, which claims priority to U.S. Provisional Patent Application No. 61/414,250, filed Nov. 16, 2010, the entire disclosure of each of these applications being incorporated herein by this reference.

[0002] The present invention pertains to methods for creating a foam-like texture on an implantable material. More particularly, the present invention relates to methods for creating foam-like texture on implantable silicone materials.

[0003] Prostheses or implants for augmentation and/or reconstruction of the human body are well known. Capsular contracture is a complication associated with surgical implantation of prostheses, particularly with soft implants, and even more particularly, though certainly not exclusively, with fluid-filled breast implants.

[0004] Capsular contracture is believed to be a result of the immune system response to the presence of a foreign material in the body. A normal response of the body to the presence of a newly implanted object, for example a breast implant, is to form a capsule of tissue, primarily collagen fibers, around the implant. Capsular contracture occurs when the capsule begins to contract and squeeze the implant. This contracture can be discomforting or even extremely painful, and can cause distortion of the appearance of the augmented or reconstructed breast. The exact cause of contracture is not known. However, some factors may include bacterial contamination of the implant prior to placement, submuscular versus subglandular placement, and smooth surface implants versus textured surface implants, and bleeding or trauma to the area.

[0005] Surface texturing has been shown to reduce capsular contracture when compared to what are known as “smooth” surface implants.

[0006] There is still a need for a more optimal surface textured implant that further reduces the potential for capsular contracture. The present invention addresses this need.

[0007] The present invention pertains to methods for creating a foam-like texture on a material that is suitable for implantation in a mammal.

[0008] In one aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0009] 1) applying a texturing material lacking a foam-like texture onto a mandrel of a desired shape;
  • [0010] 2) placing a foam-like material over the texturing material;
  • [0011] 3) applying pressure to integrate the foam-like material and the texturing material;
  • [0012] 4) allowing the foam-like texture to set in the texturing material;
  • [0013] 5) removing the foam-like material from the texturing material which has acquired a foam-like texture.

[0014] Metal rings may be used to clamp and immobilize the foam-like material as the foam-like material is pressed down on and integrated into the non-solid texturing material; the weight of the metal rings can aid in pressing the foam-like material and the texturing material together. In another variant, a base coat, which may be the same material as the texturing material, may be spread onto the mandrel and solidified before the texturing material is spread onto the base coat.

[0015] In another aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0016] 1) applying a texturing material lacking a foam-like texture onto a film coater;
  • [0017] 2) placing a foam-like material over the texturing material; p1 3) applying pressure to integrate the foam-like material and the texturing material;
  • [0018] 4) allowing the foam-like texture to set in the texturing material;
  • [0019] 5) removing the foam-like material from the texturing material which has acquired a foam-like texture.

[0020] A base coat, which may be the same material as the texturing material, may be spread onto the film coater and solidified before the texturing material is spread onto the base coat.

[0021] In another aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0022] 1) applying pressure to integrate a first texturing material lacking a foam-like texture and a foam-like material;
  • [0023] 2) allowing the foam-like texture to set in the first texturing material;
  • [0024] 3) applying pressure to integrate a second texturing material with the composite of the first texturing material and the foam-like material;
  • [0025] 4) allowing the foam-like texture to set in the second texturing material;
  • [0026] 5) removing the foam-like material from the texturing materials which have acquired a foam-like texture.

[0027] The present invention also provides a method for creating one or more foam-like-textured surfaces on a breast prosthesis or implant. A textured material, having the desired dimensions, that acquires a foam-like texture through any of the novel methods described above, can be bonded, by a suitable, biocompatible adhesive, to a smooth shell breast prosthesis, to produce a breast prosthesis having a foam-like-textured surface.

[0036] The present invention pertains to methods for creating a foam-like texture on an implantable material. More particularly, the present invention relates to methods for creating foam-like texture on implantable silicone materials. Even more specifically, the present invention relates to methods for creating polyurethane-foam-like texture on implantable silicone materials.

[0037] The present invention also relates to methods for creating one or more foam-like texture surfaces on breast prostheses or implants.

[0038] As used herein, “foam-like texture” refers to texture that is characterized by interconnected pores or the like, or texture that resembles or approximates such a texture.

[0039] As used herein, “texturing material” refers to a substantially non-biodegradable polymeric material that acquires a foam-like texture through the novel methods disclosed herein. In the “EXAMPLES” section, silicone is the texturing material. Other examples of texturing material include, but are not limited to: polyurethane, polyesters, polyolefins, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, ethylene-co-vinylacetate, polybutylmethacrylate, vinyl halide polymers and copolymers (e.g., polyvinyl chloride), polyvinyl ethers (e.g., polyvinyl methyl ether), polyvinylidene halides (e.g., polyvinylidene fluoride and polyvinylidene chloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (e.g., polystyrene), polyvinyl esters (e.g., polyvinyl acetate), copolymers of vinyl monomers with each other and olefins (e.g., ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers), polyamides (e.g., Nylon 66 and polycaprolactam), alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, rayon, ryon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, and combinations thereof. The texturing material used for the novel methods disclosed herein can be selected or enhanced based upon considerations such as resistance to acids and bases, mechanical strength, resistance to radiation, such as UV, exposure, and resistance to metal salts or solvents. As used herein, a “base coat” can be of any material that the “texturing material” can be.

[0040] As used herein, “foam-like material” refers to a material that has a “foam-like texture” and is used to impart a foam-like texture to a “texturing material” through the novel methods disclosed herein. In the “EXAMPLES” section, polyurethane foam is the foam-like material. The following are other non-limiting examples of foam-like material or material which can be used to make foam-like material: polyethylene, polyethylene vinyl acetate, polystyrene, polyvinyl alcohol, Styrofoam, polyolefin, polyester, polyether, polysaccharide, polyamide, polyacrylate; a material which contains aromatic or aliphatic structures in the backbone, as functionalities, cross-linkers or pendant groups, or a copolymer, terpolymer, or quarternaly polymer thereof; metal, metal foam, ceramic, ceramic foam, and combinations thereof.

[0041] Novel methods disclosed herein generally comprise:

• • [0042] 1) integrating a texturing material lacking a foam-like texture with a foam-like material by pressing them together;
  • [0043] 2) removing the foam-like material from the solidified texturing material which has acquired a foam-like texture.

[0044] If the texturing material is a non-solid prior to integration with a foam-like material, the texturing material would be solidified following integration.

[0045] In one aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0046] 1) applying a texturing material lacking a foam-like texture onto a mandrel of a desired shape;
  • [0047] 2) placing a foam-like material over the texturing material;
  • [0048] 3) applying pressure to integrate the foam-like material and the texturing material;
  • [0049] 4) allowing the foam-like texture to set in the texturing material;
  • [0050] 5) removing the foam-like material from the texturing material which has acquired a foam-like texture.

[0051] The above aspect of the present invention is illustrated in examples 1 and 2 in the “EXAMPLES” section. Metal rings may be used to clamp and immobilize the foam-like material as the foam-like material is pressed down on and integrated into the non-solid texturing material; the weight of the metal rings can aid in pressing the foam-like material and the texturing material together. A base coat, which may be the same material as the texturing material, may be spread onto the mandrel and solidified before the texturing material is spread onto the base coat. The step of allowing the foam-like texture to set in the texturing material may comprise solidifying the texturing material, such as by heat-curing.

[0052] In another aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0053] 1) applying a texturing material lacking a foam-like texture onto a film coater;
  • [0054] 2) placing a foam-like material over the texturing material;
  • [0055] 3) applying pressure to integrate the foam-like material and the texturing material;
  • [0056] 4) allowing the foam-like texture to set in the texturing material;
  • [0057] 5) removing the foam-like material from the texturing material which has acquired a foam-like texture.

[0058] The step of allowing the foam-like texture to set in the texturing material may comprise

[0059] solidifying the texturing material, such as by heat-curing. A base coat, which may be the same material as the texturing material, may be spread onto the film coater and solidified before the texturing material is spread onto the base coat. This embodiment is illustrated in example 3 in the “EXAMPLES” section.

[0060] In another aspect, the present invention provides a method of making a material having a foam-like texture and suitable for implantation in a mammal, the method comprising:

• • [0061] 1) applying pressure to integrate a first texturing material lacking a foam-like texture and a foam-like material;
  • [0062] 2) allowing the foam-like texture to set in the first texturing material;
  • [0063] 3) applying pressure to integrate a second texturing material with the composite of the first texturing material and the foam-like material;
  • [0064] 4) allowing the foam-like texture to set in the second texturing material;
  • [0065] 5) removing the foam-like material from the texturing materials which have acquired a foam-like texture.

[0066] This embodiment is illustrated in examples 4 and 5 in the

[0067] “EXAMPLES” section.

[0068] Types of silicones mentioned in the following examples were obtained from NuSil Silicone Technology, Carpinteria, Calif.

[0069] Uncured Room-Temperature-Vulcanizing (“RTV”) silicone, for example, MED-1511, is spread onto a mandrel of a desired shape as a layer having a thickness of 200 μm. A polyurethane foam is placed over the RTV silicone and the mandrel with the aid of metal rings which clamp the foam in place. The weight of the metal rings asserts a force of approximately 30 psi against the polyurethane foam, the RTV silicone and the mandrel. After the RTV silicone is cured, the metal ring and mandrel are removed from the composite of the cured RTV silicone and polyurethane foam. The composite of the cured RTV silicone and polyurethane foam is submerged in hydrochloric acid for five minutes to remove the polyurethane foam. Excess hydrochloric acid is removed by washing in distilled water for two minutes. The resulting product is a silicone material having a foam-like texture.

[0070] A base coat of uncured High-Temperature-Vulcanizing (“HTV”) silicone dispersed in xylene, for example, MED-6400 dispersed in xylene, is spread onto a mandrel and cured (in FIG. 1, the “silicone base material”). The mandrel covered by a base coat is then dipped in a second uncured HTV silicone dispersed in xylene (in FIG. 1, the “silicone texturing material”), for example, MED 6640 in xylene, until the second coat of HTV silicone dispersed in xylene reaches a thickness of (about) 250 μm. Then the xylene is removed from the HTV silicone materials by devolatilization in a fume hood. Next, a piece of polyurethane foam is placed over and pressed down against the HTV-silicone-coated mandrel. One way to apply the polyurethane foam to the HTV-silicone-coated mandrel is to clamp the foam between metal rings (see FIG. 1), then place the exposed portion of the foam that is circumscribed within the rings over the mandrel; the metal rings immobilize the foam to keep it in place and press the foam against the HTV-silicone-coated mandrel. With the polyurethane foam integrated into the second coat of HTV silicone, the second coat of HTV silicone is heat-cured. After the silicone has been cured and acquired the texture of the polyurethane foam, the polyurethane foam is removed by application of acid or hot solvent.

[0071] An uncured silicone material (1 mm thick, 5″×5″), such as MED-4815 dispersed in xylene (50 ml, 30% w/w), is cast onto a Teflon sheet on the surface of a film coater. After the film coater creates an even sheet of the silicone, the Teflon sheet is taken off of the film coater and the silicone is cured in an oven at 126° C. for 2 hours. The Teflon sheet with the cured, first layer is then placed back on the film coater. Then, an uncured, second layer of silicone material, which maybe the same material as the cured, first layer, is spread onto the surface of the cured, first layer. The film coater creates an even sheet of the uncured second layer of silicone. The Teflon sheet is then removed from the film coater and placed in a mechanical press. Next, polyurethane foam is placed over the uncured, second layer of silicone material and, using the press set to 50 psi, the polyurethane foam is pressed into the uncured silicone for 1 minute, which results in a 70% integration. “% integration” as used herein refers to the percent of the thickness of the texturing material that the foam-like material is pressed into. The uncured silicone is then cured at 126° C. for 1 hour and acquires the texture of the polyurethane foam. The Teflon sheet is then peeled off of the cured silicone and discarded. The polyurethane foam is removed from the cured silicone by washing the polyurethane-silicone composite in 300 ml of 38% concentrated HCI for 5 minutes, followed by a 3-minute wash in distilled water. FIG. 2 shows the layers of material on the Teflon surface of the film coater: the “base material” is the first layer of silicone material; the “texturing material” is the second layer of silicone material which acquires the texture of the polyurethane foam.

[0072] Using a press set to 60 psi, polystyrene-block-polyisoprene-block polystyrene (“polystyrene foam”) is pressed into an uncured, 1 mm-thick sheet of a silicone material, such as MED-4810. The silicone is then cured at 100° C. for 2 hours, generating a cured silicone-polystyrene foam composite. A dilute second silicone material, which may be the same as or different from the first, such as MED-4810 dispersed in dichloromethane (10% w/w), is poured onto the cured silicone-foam; the cured silicone-foam coated with uncured silicone is immediately pressed for 5 seconds under a pressure of 40 psi between two Teflon or aluminum sheets. Next, the uncured silicone coating the cured silicone-foam is cured at 100° C. for 1 hour. The polystyrene foam is removed from the silicone by soaking the silicone in 200 ml of hexane overnight.

[0073] First, a polyurethane sheet is completely submerged in a bath of silicone dispersed in xylene, for example, MED-4714 dispersed in xylene (10% w/w); the fully-submerged polyurethane sheet is pressed at 20 psi to enable the silicone dispersion to fully enter and saturate the polyurethane. The polyurethane sheet is then removed from the bath and excess silicone dispersion is allowed to run off of it. The silicone-polyurethane composite is then cured at 120° C. for one hour. The cured silicone-polyurethane composite is then pressed, at a pressure of 40 psi, into an uncured, 2 mm-thick sheet of a second silicone material, for example, MED-4815. The uncured second silicone material coating the cured silicone-polyurethane composite is cured at 120° C. for one hour, resulting in silicone that has acquired the foam-like texture of the polyurethane. The polyurethane is then removed from the silicone materials by dipping the silicone-polyurethane composite in DMSO (at 130° C.) for 20 minutes.

[0074] In some embodiments, suction can be used as an aid in integrating the foam-like material and the texturing material. Suction can be applied to a foam-like material to pull the texturing material, for example, silicone in solvent, through the foam-like material. The more integrated the foam-like material and the texturing material, the thicker the foam-like texture that is created in the texturing material. Suction can also remove any excess texturing material, meaning texturing material beyond that which is sufficient to saturate the foam-like material, or texturing material that has not smoothly integrated into the foam-like material, but is instead blocking the pores of the foam-like material.

[0075] In some embodiments, the foam-like texture created in a texturing material, such as a silicone material, through the novel methods disclosed herein may be heterogeneous, as opposed to homogeneous. A “homogeneous” foam-like texture generally refers to a texture having approximately the same number of interconnections per pore (see Fig. for illustration of “interconnections”). A “heterogeneous” foam-like texture generally refers to a texture having variation in the number of interconnections per pore.

[0076] An example of a heterogeneous foam-like texture that can be created in a texturing material would be a texture comprising a gradient of interconnections between pores: there is an increase in the number of interconnections per pore from one surface of the texturing material to the opposing surface (see FIG. 4A). In a cross section view, a texturing material having acquired a foam-like texture with a gradient of interconnections would resemble a closed cell foam at one end, but an open cell foam at the other end, with pores closer to the end resembling an open cell foam each having more interconnections than pores closer to the end resembling a closed cell foam (see FIG. 4A). A closed cell foam is generally characterized as having two or fewer interconnections per pore and an open cell foam as having three or more interconnections per pore (see FIG. 5).

[0077] For example, a heterogeneous foam-like texture can be created in a texturing material, such as silicone, if excess silicone, meaning more silicone than is necessary to saturate the foam-like material, is used. Because the silicone is in excess, the bottom surface of the silicone, which is the surface opposite the top surface onto which the foam-like material was pressed, would be a layer of silicone containing few or no pores; however, there are more and more pores and more interconnections per pore closer to the surface of the silicone onto which the foam-like material was pressed.

[0078] Whether and to what degree a texturing material acquires a heterogeneous foam-like texture can be due to many different factors, such as the amount of texturing material used relative to the foam-like material, the concentration of texturing material in solvent, the amount of pressure used to press the foam-like material and texturing material together, and changing the amount of solvent in which the texturing material is dispersed when the foam-like material is pressed against the texturing material.

[0079] The foam-like material used to impart a foam-like texture to a texturing material may have about 1% to about 99% porosity. As used herein, “% porosity” refers to % of the total volume of the foam-like material that comprise void or empty space. Consequently, a texturing material that has acquired a foam-like texture from a foam-like material may have about 1% to about 99% porosity.

[0080] The foam-like material may have a pore size of about 100-1000 μm (relative standard deviation (“RSD”) of about 0.01-100%); an interconnection size of about 30-700 μm (RSD of 0.01-100%); interconnections per pore of about 2-20 (RSD of 0.01-50%); and an average pore to interconnection size ratio of about 3-99%.

[0081] In some embodiments, the foam-like material has a pore size of about 300-700 μm (RSD of 1-40%); an interconnection size of about 100-300 μm (RSD of 1-40%); interconnection per pore of about 3-10 (RSD of 1-25%) and an average pore to interconnection size ratio of about 10-99%.

[0082] In an exemplary embodiment, the foam-like material comprises a material, for example, polyurethane or other suitable material, having a pore size of 472+/−61 μm (RSD=13%), interconnection size of 206+/−60 μm (RSD=29%), interconnection per pore of 9.6+/−1.8 (RSD=19%), and pore to interconnection size ratio of 44%.

[0083] The texturing material can be solvent-free or dispersed in solvent when applied to a foam-like material for integration. One example of a texturing material that does not require dispersion in solvent is Room-Temperature-Vulcanizing silicone. The concentration of texturing material in solvent can range from about 5 to about 100% w/w. The greater the concentration of texturing material in solvent, the greater the density (mass per unit volume) of the end product, the texturing material which has acquired a foam-like texture, such as a silicone material that has acquired a foam-like texture. Non-limiting examples of useful solvents include acetone, xylene, dichloromethane, chloroform, dimethyl sulfoxide, water, methanol, methyl acetate, hexane, benzene toluene, and isopropyl alcohol.

[0084] The texturing material can be a solid, for example, an RTV silicone, or fluid material. Fluid materials include dispersions, solutions, emulsions, or a combination thereof. The viscosity of fluid texturing materials may range from approximately 10 to 3,000,000 cP.

[0085] Pressure applied to integrate a texturing material and foam-like material may range from 0.5 to 500 psi. In other embodiments, the pressure may range from 1 to 200 psi. Generally, the greater the pressure applied, the greater the degree of integration between the texturing material and the foam-like material, and the greater the extent and thickness of the foam-like texture layer that is created in the texturing material. Thus, the pressure can be varied depending on how extensive of a foam-like texture is desired to be created in the texturing material.

[0086] FIGS. 6A & 6B are SEM micrographs showing the foam-like texture of a silicone material, MED-2000, that acquired its foam-like texture from polyurethane foam under the high pressure of 100 psi. 6A is a cross-sectional view and 6B is a top view.

[0087] FIGS. 7A & 7B are SEM micrographs showing the foam-like texture of a silicone material, MED-2000, that acquired its foam-like texture from polyurethane foam under the low pressure of 10 psi. 7A is a cross-sectional view and 7B is a top view.

[0088] Because greater pressure was applied for the silicone texturing material shown in FIG. 6 than that shown in FIG. 7, there is a greater degree of integration for the one in FIG. 6 (compare, for example, the cross sectional images in 6A with that in 7A; the foam-like texture layer that is created is thicker in 6A than in 7A).

[0089] Also, the morphology of the foam-like material may change if too great a pressure is exerted to integrate the foam-like material and the texturing material, which would affect the foam-like texture that is created in the texturing material as well. What counts as too great a pressure depends on foam-like and texturing materials used; a set of foam-like and texturing materials pressed together under a certain pressure would result in the texturing material acquiring foam-like characteristics that differ from those it would acquire if pressed at a higher pressure.

[0090] If the texturing material used is dispersed in solvent, the type of solvent can affect the time it takes to integrate the texturing material and the foam-like material. For example, it generally takes less time to integrate a RTV silicone dispersed in dichloromethane with a foam-like material than a HTV silicone dispersed in xylene with a foam-like material.

[0091] Also, the foam-like material may swell when contacted with the solvent in which the texturing material is dispersed, and this can alter the texture of the foam-like material and hence the foam-like texture that the foam-like material imparts to the texturing material.

[0092] The process for removing the foam-like material after the foam-like material has imparted a foam-like texture to the texturing material varies depending on the foam-like material used. Any means known to those of skill the art and suitable for removing the foam-like material without substantially affecting the texturing material that has acquired a foam-like texture may be used. Agents used for removal may be a base, a solvent, an enzyme, an acid, heat, oxidation, uv light, gamma irradiation, visible light, infrared light or a combination thereof. When the foam-like material used is polyurethane, the polyurethane may be removed by, for example, dimethyl sulfoxide, hydrogen peroxide, hydrochloric acid, dimethyl formamide, acetone, or a combination thereof. The removing process may not remove all of the foam-like material all at once, so it may be repeated as desired.

[0093] The present invention also provides a method for creating one or more foam-like-textured surfaces on a breast prosthesis or implant. A textured material, having the desired dimensions, that acquires a foam-like texture through any of the novel methods described above, can be bonded, by a suitable, biocompatible adhesive, to a smooth shell breast prosthesis, to produce a breast prosthesis having a foam-like-textured surface.

[0094] In some embodiments, the methods disclosed hereinbefore may be used to create a foam-like texture on material that has already been textured through other means. For example, a texturing material, such as a silicone material, may undergo a texturing process as described in U.S. Pat. No. 5,007,929 (“Quaid patent”), which is incorporated by reference herein, before it undergoes any of the methods disclosed hereinbefore to acquire a foam-like texture.

[0095] In some embodiments, a breast implant may have a very thin, for example, 0.5 mm-thick, texturing material having a foam-like texture bonded to its front surface and a thicker, for example, 3 mm-thick, texturing material having a foam-like texture bonded to its back surface. Generally, the thickness of the texturing material having a foam-like texture used for bonding to surface(s) of breast implants can vary between approximately 0.1 to 50 mm. The foam-like material used to create texturing materials having a foam-like texture for bonding to surface(s) of breast implants can vary between approximately 0.1 to 250 mm thick.