WO2016057575A1 - Expanded polytetrafluoroethylene covered breast implants to minimize capsular reaction and infection while reducing palpability - Google Patents
Expanded polytetrafluoroethylene covered breast implants to minimize capsular reaction and infection while reducing palpability Download PDFInfo
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- WO2016057575A1 WO2016057575A1 PCT/US2015/054320 US2015054320W WO2016057575A1 WO 2016057575 A1 WO2016057575 A1 WO 2016057575A1 US 2015054320 W US2015054320 W US 2015054320W WO 2016057575 A1 WO2016057575 A1 WO 2016057575A1
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- eptfe
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/12—Mammary prostheses and implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/04—Materials or treatment for tissue regeneration for mammary reconstruction
Definitions
- Implants can be used to augment particular areas of the human body, such as calves, breasts and others. Implantation of implants can be used for reconstructive purposes or cosmetic purposes. For breast implants, reconstructive implantation purposes can include implantation after mastectomy for breast cancer, where a woman has had one or both breasts removed, while cosmetic reasons for implantation can include to change the size, firmness, or shape of the breast or for other aesthetic reasons.
- Glaline implants can include silicone shells filled with sterile salt water such as saline.
- Silicone implants can include silicone shells filled with silicone gel. Implantation procedures typically involve a surgeon making an incision under the breast, under the arm or around the nipple and then implanting the implant into a pocket or capsule above or below the chest muscle. The surgeon then closes the incisions with sutures.
- FIG. 1 shows a top view of an example embodiment of a prior art breast implant.
- FIG. 2 shows a top view of a cross section of an example embodiment of a breast implant with an ePTFE layer.
- FIG. 3 shows an exploded cross-sectional view of an example embodiment of a breast implant with ePTFE coating and adherence layer, along the plane indicated by the line 3 in FIG. 2.
- FIG. 4 shows a cross-sectional view of an example embodiment of a breast implant with an ePTFE with mechanical adhering.
- FIG. 5 shows a side cross-sectional view of a fibrous capsule in conjunction with an example embodiment of a breast implant just after implantation and before development of an intima.
- the present invention relates to improved methods, systems and implant devices having minimal capsular reaction, infection prevention and reducing palpability along with other benefits. While these methods, systems and devices are particularly suited for breast implants, it should be understood that the disclosure herein is not limited to such environments and can be used in other implantation methods, systems and devices with similar concerns.
- FIG. 1 shows a top view of an example embodiment of a prior art breast implant.
- a breast implant 12 is shown.
- Breast implants 12 can be silicone implants or saline implants as currently known in the art.
- breast implants 12 are generally round, having a substantially standard radial diameter from a center point as viewed from a top down perspective.
- FIG. 2 shows a top view of a cross section of an example embodiment of a breast implant 11.
- a breast implant 11 can include an implant 12 having an exterior layer of silicone as is known in the art or later developed, surrounded by an ePTFE (expanded polytetraflouroethylene, also known as Gore-Tex® by W. L. Gore & Associates, Inc.) layer 17 having a plurality of micropores 21.
- An interface 18 between implant 12 and ePTFE layer 17 can include mechanical (e.g. see FIG. 4), adhesive (e.g. see FIG. 3), or other coupling means by which the ePTFE layer 17 is adhered to the surface of the implant 12.
- ePTFE in the first white, soft, lightweight and covered breast implants can be distinguished from the prior art. Current breast implants are typically clear, can be firm and do not provide an outer covering. Use of ePTFE as an implant covering can provide mental and psychological benefits for patients contemplating surgery since they receive peace of mind in feeling the light weight of the implants and the soft surface that will be in contact with their internal tissues. The white exterior can also resemble a cloud, further allaying some psychological issues.
- FIG. 3 shows an exploded cross-sectional enlarged view of an example embodiment of a breast implant with ePTFE coating 17 and silicone layer 12 including an interface 18, along the plane indicated by the line 3 in FIG. 2. Although spaces (not labeled) are shown in FIG. 3 between ePTFE coating 17, interface 18 and silicone layer 12, these are merely to facilitate viewability of the Figure and would be understood by those in the art as being minimal or nonexistent in actual embodiments.
- interface 18 can be one or more layers or mixtures of chemical glues or adhesives can be used to attach or adhere ePTFE layer 17 and similar layers of compounds to silicone layer 12.
- interface 18 can be an alloplastic implant material, an example of which is described by Berman et al. in: "The use of Goretex e-PTFE bonded to silicone rubber as an alloplastic implant material.” Laryngoscope (1986): 96(5), pp4 80-3 which is hereby incorporated in its entirety by reference.
- interface 18 can be a proprietary bonding of ePTFE to Silicone.
- ePTFE Teflon
- Silicone® An example of a PTFE (Teflon) bonded Silicone which is referred to as ITW Teflon Bonded Silicone®, and described in the Technical Data Sheet "Introducing Patent Pending ITW Teflon Bonded Silicone” was developed by ITW United Silicone of Lancaster, NY and which is hereby incorporated in its entirety by reference.
- PTFE also known as Teflon
- Teflon has some similar characteristics to ePTFE.
- a method of attaching, bonding or otherwise coupling PTFE (Teflon) to silicone while also reducing problematic issues with seams can be found in the patent application PCT Publication
- WO/2014/116490 Al titled “Silicone E-spun PTFE Composites” and filed January 16, 2014, invented by Ballard et al and applied for by Zeus Industrial Products, Inc. of Orangeburg, South Carolina, which is hereby incorporated in its entirety by reference.
- electro-spin porous, polymeric components such as PTFE, can be created around a silicone component and make a composite of PTFE that is adhered to silicone.
- FIG. 4 shows an exploded cross-sectional view of an example embodiment of a breast implant surface with an ePTFE coating 17 and silicone layer 12 including an interface 18 with a plurality of mechanical coupling elements 19, along the plane indicated by the line 3 in FIG. 2.
- mechanical linking of ePTFE and Gore-Tex can be accomplished using mechanical coupling elements 19 or otherwise structural components which can have caltrop or tetrapod shapes and can have varied orientations in different embodiments.
- distribution and orientation of mechanical coupling elements 19 can be standardized or repetitive.
- Various additional features of mechanical coupling elements 19 are contemplated include hooks, fasteners, protrusions, and others.
- both adhesives and mechanical components 19 can be used at interface 18 and in some embodiments mechanical components 19 can be treated with adhesives.
- mechanical linking of PTFE (Teflon) or ePTFE (Gore-Tex) and silicone can include application of zinc oxide nanocrystals (ZnONC) or other materials with caltrop or tetrapod shapes that link opposing surfaces of an ePTFE layer and a silicone layer.
- the mechanical components 19 can be placed between ePTFE layer 17 and silicone layer 12 before applying heat to one or both layers at the same time. This can cause the mechanical components 19, also known as nanostructure anchors, to imbed at least partially into both layers, thus holding the two layers together.
- metal oxide nano-, micro- or nano-micro-structures which can "join two extremely diffi cult-to-join polymer layers, namely poly(tertafluorethylene) (PTFE) and cross-linked poly(dimethyisiloxane) (PDMS),” as described in an article by Dodson, published August 26, 2012 on www.gizmag.com titled: "Bringing Teflon and silicone together shows promise for medical applications," which is hereby incorporated in its entirety by reference. See: http://www.gizmag.com/teflon-silicone- binding/23872/.
- complex shaped metal oxide nano-structures can create interconnected networks which can be applied to surfaces for linking materials.
- An example is described by Mishra et al in: "Versatile Fabrication of Complex Shaped Metal Oxide Nano- structures and Their Interconnected Networks for Multifunctional Applications," Kona Powder and Particle J., No. 31, (2014) pp. 92-110, which is hereby incorporated in its entirety by reference.
- adhesion between low surface energy polymers can be accomplished using tetrapodal ZnO components.
- tetrapodal ZnO components An example is described by Jin et al in: "Joining the un-joinable: Adhesion between low surface energy polymers using tetrapodal ZnO linkers," Adv. Mater., Vol. 24, (2012) pp. 5676-5680 which is hereby incorporated in its entirety by reference.
- FIG. 5 shows a side cross-sectional view of a fibrous capsule 24 in conjunction with an example embodiment of a breast implant 11 having an ePTFE coating 17 and silicone layer 12 just after implantation and before development of an intima.
- ePTFE layers 17 as shown in FIGs. 2-5 or similar surfaces can serve as a soft, pliable, microporous (e.g. micropores 21 shown in FIGs. 2-3), smooth outer layer of a breast implant or other implant, providing numerous beneficial properties over the prior art as described herein.
- an entire implant can be comprised of ePTFE (not shown) as opposed to merely using it as a coating as shown in FIGs. 2-5.
- an ePTFE implant can be an implant with a silicone surface, known in the art as a polysiloxanes implant and filled with a silicone gel or saline, where the silicone surface can be smooth or textured in various embodiments and has a constant or varying thicknesses of an outer layer of ePTFE or similar coating applied to the silicone surface at an interface.
- ePTFE or Gore-Tex has a microporous framework with a porosity of about 10-30 microns, averaging about 22 ⁇ in diameter as described in ePTFE Implants in Rhinoplasty: Literature Review, Operative Techniques, and Outcome, Ham J., Miller P. Facial Plastic Surgery 2003; Vol. 19, No. 4, which is hereby incorporated in its entirety by reference.
- These microporous framework characteristics, along with non-stick or electronegative and favorable biocompatible properties of ePTFE can help ePTFE resist tissue ingrowth which can be beneficial in various embodiments. Tissue ingrowth can cause tissue adherence to an implant surface of prior art implants and can thwart any postoperative implant movements.
- ePTFE coating layer can prevent this tissue adherence, allowing for postoperative implant movements by a patient, nurse, surgeon, doctor or other healthcare worker.
- postoperative implant movements can provide numerous benefits, at least one of which is that this can result in the forming of a post-operative scar capsule with a larger three-dimensional structure than the actual physical three-dimensional size of the implant with the ePTFE coating.
- micro-structured gaps as described above and also referred to herein as micro-pores (e.g. micro-pores 21 in FIGs. 2-3), in ePTFE layers of an ePTFE coated or ePTFE implant can also serve as reservoirs for various chemicals in the surface of the ePTFE. These chemicals, along with the soft, smooth characteristic of ePTFE, can serve to optimize biological acceptance of the implant and minimize risk of capsular contracture which will be further described below.
- delivery chemicals or substances implanted, stored or otherwise located in the micro-structured gaps of a treated ePTFE implant can assist in implant delivery or other implantation procedures by allowing for and enabling the use of a more slippery surface than currently available.
- This can be accomplished by a manufacturer applied or pre-operative treatment and maintenance a surface chemical or peri-implant space material in the micro-pores of the ePTFE surface, unlike the current state of the art that provides only for secondary treatments to implant surfaces.
- This pre-treatment or primary treatment can also encourage movement of the implant within an implant capsule and thus provide for the benefits of larger post-operative capsule formation, the benefits of which were described above.
- chemicals or other substances that can act to discourage immediate and prolonged tissue adherence can be applied and maintained in the micro-structured gaps.
- These surface chemicals or peri-implant space materials can function similar to several chemicals, substances or materials which are known in the art but are not integrated with a physical surface of an implant currently because they are merely applied as a secondary treatment to an implant surface.
- these secondary treatments of implant surfaces can include: a) a hydrophilic inner layer of a Keller funnel; b) a lubricating material in refresh drops, such as carboxymethylcellulose sodium/glycerin/polysorbate 80; and c) a synthetic synovial fluid.
- These secondary treatments as referred to herein are treatments applied to implants that typically occur at or near the time of implant delivery or implantation.
- the current ePTFE pre-treated or primary treated surface which is microporous and can maintain one or more chemicals or substances can also be used in conjunction with any of the secondary treatments as well, in order to provide additional benefits.
- additional or alternatively applied surface chemicals or peri-implant space materials can include at least: a) antibiotics, such as Rifampin and others; b) calcium channel blockers, such as Verapamil and others; c) Vitamin E, including the synthetic form alpha-tocopherol; d) Methylprednisolone and others; and e) others.
- Surface chemicals or peri-implant space materials can also optimize conditions for cellular adhesion and growth on an outer surface of implants for creation of an intima, bursa, and synovial environment as opposed to integration by the tissue around the implant. These chemicals, substances or materials can include one or more of: a) Synovial fluid-like material; b) Pre-treatment with alcohol or c) others.
- ePTFE reservoirs in the form of micropores can allow chemicals to be layered in and on the ePTFE surface, especially in embodiments where a layer of ePTFE of an implant is relatively thick.
- an external substance layer can be coated on an outer, external ePTFE implant surface to help optimize slippery characteristics of the ePTFE implant as would be beneficial in the first few days or weeks after an implantation procedure. This coating layer can dissipate over time and be appropriately absorbed by the body.
- a secondary or intermediate layer can be presoaked by a surgeon or otherwise implanted in the ePTFE reservoirs or surface by a manufacturer, typically prior to the external substance layer.
- the secondary or intermediate layer can include an antibiotic layer or inhibitory layer which can serve to prevent or inhibit bacterial infection or infections caused by other biological pathogens.
- a tertiary layer or other deeper layer or layers can be applied prior to the secondary or intermediate layers and external layers.
- the tertiary layer or deeper layers can include chemicals, substances and materials which can be expressed, released or administered more slowly, over a longer time or at a delayed time and can assist with cellular adhesion in order to help create a beneficial intima as a bursa or synovial type environment.
- Application or implantation of chemical, substance or material layers can be accomplished while accounting for particular timing, interaction, heating, cooling or other chemical, substance or material specific concerns taken into consideration during the pre-treatment or primary treatment process, as would be understood by those in the art.
- a thick or contracting scar capsule around an implant can be an undesirable side effect of implantation because it can cause numerous problems including: pain, hardness, and significant distortion of external anatomy. Additionally it can cause electrical disturbance and decreased lifespan of wires associated with internal defibrillators and pacemakers.
- an implant with at least one ePTFE surface can beneficially minimize tissue adherence problems associated prior art implants including capsular contracture.
- Microporous ePTFE surfaces can provide smooth, soft and biocompatible surfaces that can move easily in a capsular 'pocket' after implantation and thus produce a thin capsule size which can be larger in physical volume size without increased thickness of capsular walls.
- ePTFE micropores can provide an inhibitory effect on microbial contaminant growth with or without antibiotic soaking and thus can be correlated with lower capsular contracture rates.
- a solution of Fluorocarbons can be applied to an ePTFE layer of an implant and thus inhibit the creation of a bio film or other undesired bacterial layer or frank infection. Fluorocarbon coated implants have been described by Karlan et al in Potentiation of Infections by Biomaterials: a comparison of three materials. Otolaryngol Head Neck Surg. 1981; 89:528-534, which is hereby incorporated in its entirety by reference, as having a significantly decreased infection rate when compared to silicone.
- ePTFE or Gore-Tex layers can also reduce problems associated with capsular contracture using other mechanisms.
- Microporosity can be optimized for particular facilitating environments in which the optimized microporous ePTFE layers can allow for topical cellular growth outward or around the ePTFE implant in different amounts and at different rates. This is in direct contrast with 'tissue integration' in prior art implants in which the tissue grows into and fixes a location of the implant.
- an ePTFE implant can develop a monocellular or multicellular 'intima' (not shown) over the ePTFE surface of the implant.
- the relationship of the implant with the capsule can perform similarly to performance of naturally occurring biological environments in which a bursa or synovial type environment has two biological membranes opposing each other.
- a bursa or synovial type environment has two biological membranes opposing each other.
- one can be a biological membrane capsule and one can be a biological membrane intima around the ePTFE implant.
- this type of environment can be a beneficial structural environment: "[i]nterestingly, the macroscopically smooth-surface implant also presents with a rippled microscopic texture on the surface, which might increase the formation of a synovial-type epithelium, experienced in fibrotic breast capsules.”
- an intima can be described as follows: "[a]s a rule, host cells do not adhere directly to the surface of synthetic implanted materials. Extracellular proteins and proteoglycans form a substrate to which the cells attach. Interactions with cell membrane receptors furnish the linkage for cellular attachment to adsorbed extracellular matrix proteins on implant surfaces. The predominant cells that attach to the protein layer are the fibroblasts. The fibroblasts lay down immature collagen over the matrix on the implant and into the interstices of porous implant.
- an ePTFE implant can be safer from a medical standpoint for users receiving it as an implant.
- One or more ePTFE layers adhered to a silicone implant can serve to create an additional barrier to leakage of silicone gel out of a silicone implant when used with a silicone implant.
- users can have a reduced chance of negative tissue reaction due to failure of a silicone implant than with traditional silicone implants.
- one or more layers of ePTFE can greatly reduce any penetration of silicone into surrounding tissue since silicone particles are unable to pass through an ePTFE layer because the micropores in an ePTFE layer are smaller in diameter than the diameter of silicone particles. This can reduce or eliminate problems with silicone particles and silicone-laden macrophages in a capsular environment. Some of these problems are described by Prantl et al, including increased capsular thickness as correlated with an increase in silicone particles and silicone-laden macrophages in a capsule.
- An ePTFE or Gore-Tex covering over silicone implants can also provide a more natural 'feel,' more similar to a natural breast than current silicone gel implants without ePTFE. This advantage occurs by providing a softer cushion for finger touch due to the soft nature of ePTFE compared to silicone while also minimizing creation and feel of silicone rubber shell undulations, folding and rippling.
- ePTFE covered silicone implants can be lighter in weight than current, fully silicone implants of similar size, especially in embodiments where a thicker layer of ePTFE covering is provided. This is due to the fact that the density of ePTFE can be as low as ⁇ 0.1 gm/ml, with a porosity of 96%, while the density of a silicone gel implant is about .97gm/ml. and the specific gravity of saline is 1 gm/ml. Thus, the density of a quantity of ePTFE can be at least 9.7% less dense tha a similar quantity of silicone and at least 10% less de se than a similar quantity of saline.
- T he effect of pro viding implants with ePTFE that are lighter that other implants can make the implants easier to carry for most patients, decrease neck and shoulder pain sometimes associated with heavier breasts due to implants, and decrease breast ptosis and associated inframammary intertrigo.
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- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
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Abstract
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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MX2017004506A MX2017004506A (en) | 2014-10-06 | 2015-10-06 | Expanded polytetrafluoroethylene covered breast implants to minimize capsular reaction and infection while reducing palpability. |
EP15848612.6A EP3197395A4 (en) | 2014-10-06 | 2015-10-06 | Expanded polytetrafluoroethylene covered breast implants to minimize capsular reaction and infection while reducing palpability |
BR112017007164A BR112017007164A2 (en) | 2014-10-06 | 2015-10-06 | Expanded polytetrafluoroethylene-covered breast implants to minimize capsular reaction and infection while reducing palpability |
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US201462060480P | 2014-10-06 | 2014-10-06 | |
US62/060,480 | 2014-10-06 | ||
US201462206704P | 2014-10-21 | 2014-10-21 | |
US62/206,704 | 2014-10-21 |
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PCT/US2015/054320 WO2016057575A1 (en) | 2014-10-06 | 2015-10-06 | Expanded polytetrafluoroethylene covered breast implants to minimize capsular reaction and infection while reducing palpability |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4820303A (en) * | 1984-08-30 | 1989-04-11 | Daniel Brauman | Implantable prosthetic devices |
US5770734A (en) * | 1991-04-29 | 1998-06-23 | American Home Products Corporation | N-substituted-2-aminoquinolines useful for treating hypofunction of the cholinergic system |
-
2015
- 2015-10-06 WO PCT/US2015/054320 patent/WO2016057575A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4820303A (en) * | 1984-08-30 | 1989-04-11 | Daniel Brauman | Implantable prosthetic devices |
US5770734A (en) * | 1991-04-29 | 1998-06-23 | American Home Products Corporation | N-substituted-2-aminoquinolines useful for treating hypofunction of the cholinergic system |
Non-Patent Citations (2)
Title |
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JIN, X ET AL.: "Joining the un-joinable: Adhesion between low surface energy polymers using tetrapodal ZnO linkers.", ADVANCED MATERIALS., vol. 24, 2012, pages 5676 - 5680, XP055324022 * |
See also references of EP3197395A4 * |
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