EP2217292A1

EP2217292A1 - Surgical prosthesis for plastic reconstruction

Info

Publication number: EP2217292A1
Application number: EP08845613A
Authority: EP
Inventors: Patrick O'leary
Original assignee: Individual
Current assignee: Individual
Priority date: 2007-10-29
Filing date: 2008-10-28
Publication date: 2010-08-18
Also published as: WO2009056542A1; US20100234945A1; FR2922773A1

Abstract

Surgical prosthesis (10; 20; 30) designed to be implanted in a body for the purpose of plastic reconstruction, said prosthesis (10; 20; 30) being in contact with tissues of the body, said prosthesis (10; 20; 30) having an outer surface (12; 22; 32) which is hydrophilic in order to at least partially prevent the attachment and/or development of bacteria, especially of the hydrophobic type, on said outer surface (12; 22; 32).

Description

Surgical prosthesis for plastic reconstitution

The present invention relates to a prosthesis intended to be implanted in a human body for plastic reconstitution, and more particularly to a soft tissue body prosthesis, and more specifically to a prosthesis or a breast implant. A well-known problem with breast implants is capsular contracture. The formation of a capsule around a foreign object placed in the body is a normal consequence of implantation. Capsular contracture is the condition that occurs in approximately 5% of women, and in which the capsule surrounding the implant contracts in an attempt to isolate the implant from the rest of the body because a bacterial infection has occurred. developed. If this capsular contracture is not treated, it can lead to extrusion or permanent damage to the implant. Silicone elastomers have long been used in the manufacture of devices that can be implanted in the human body because they are chemically stable with the body as well as non-toxic.

However, despite the relatively inert nature of silicone elastomers, these can cause a foreign body reaction in some patients. When a foreign substance enters a human tissue, the natural and immediate reaction of the tissues surrounding the foreign substance is to render it harmless to the rest of the body. An inert and bulky foreign body is thus encapsulated in a layer of fibrous tissue to isolate it from surrounding tissues. This is a defense mechanism that occurs in a process similar to the formation of scar tissue following an injury or surgical incision. A fibrous tissue capsule will form around and completely surround an implanted device, such as a permanent prosthesis, and this in an intimate manner by conforming to the respective shapes and curves of the implanted device.

Many hypotheses have been proposed to explain the mechanism of capsular contraction. However the most likely mechanism involves a sub-clinical infection where bacteria normally present to a certain extent on the skin, are introduced on the surface of the silicone implant during the placement of the implant. These bacteria grow slowly and produce a bio film on the surface in contact with the surrounding tissues of the prosthesis. Organisms comprising the bio film can release exotoxins that can have a broad-spectrum effect both locally and systemically. One of these effects is the irritation of the capsule. It is assumed that when the capsule is irritated, the body's immune response attempts to isolate the implant to resolve the problem which may result in capsular contracture. The bacteria responsible for capsular contracture are usually slow-growing and highly hydrophobic bacteria to resist drying out of the skin. An example of such skin bacteria often isolated in association with capsular contracture is Staphylococcus epidermitis. This bacterium is an opportunistic bacterium that is not normally associated with an infection. It can, however, produce a bio film surrounding the bacteria that can be protective of the environment. The bacteria will preferably attach to a solid support and can then multiply. The bio film layer is the virulence factor that allows Staphylococcus epidermitis to survive where other bacteria are destroyed by the normal immune system. The bacteria can live for long periods of time with low metabolic rate.

It is almost impossible to completely sterilize the skin. The number of organisms can be reduced, but complete eradication is impossible. As a result, there will always be bacteria on the skin that can contaminate the surgical field. The bacterium Staphylococcus epidermitis can therefore attach to the silicone implant, especially during implantation, when a relatively large implant has passed through a small relative incision in the skin. The implant becomes colonized by the bacterium because of the high hydrophobicity of the external surface of the implant, (generally silicone for soft tissue prostheses) and the surface of the bacterium are both highly hydrophobic, and attract solids in a non-specific way. This allows the information of a bio film to slow growth on the external surface of the implant. Since these bacteria grow slowly, they can adhere to the external surface of the implant, remain dormant during periods of time equilibrium with the host, sometimes for several years, and then, for example, because of stress on the body, the bacteria stops living in balance with the body's immune system. At this time, under such imbalanced trigger conditions, the bacterium can rapidly replicate or at least exude exotoxins into its environment and cause inflammation on and around the capsule. Typical triggering conditions include loss or decrease in immune status due to diseases, drug treatments, etc., which will allow the bacteria to multiply.

EP-0 057 033 and FR-2 822 383 describe methods for modifying the surfaces of breast implants. These methods are complex and therefore expensive to implement.

The present invention aims to provide a prosthesis intended to be implanted in a human body for plastic reconstitution, which does not reproduce the aforementioned drawbacks.

More particularly, the present invention aims to provide a prosthesis, including a silicone breast prosthesis, for which the risks of capsular contracture are reduced.

The present invention also aims to provide such a prosthesis which is simple and inexpensive to manufacture and to achieve, and which does not require modifications of the implantation process by the surgeon. The present invention therefore relates to a surgical prosthesis intended to be implanted in a human body, as described in claim 1.

Advantageous embodiments are described in the dependent claims. These and other features and advantages of the present invention will become more apparent in the following detailed description of several embodiments, with reference to the accompanying drawings, given by way of non-limiting examples, on which

Fig. 1 is a cross-sectional view of a portion of a prosthesis, where the outer surface of the prosthesis is a silicone elastomer which is chemically modified to render it hydrophilic;

Fig. 2 is a cross-sectional view of a portion of a prosthesis having a plurality of hydrophilic microparticles partially embedded in the outer surface of the prosthesis; and

Figure 3 is a cross-sectional view of a portion of a prosthesis having a hydrophilic layer coated on the outer surface of the prosthesis.

The present invention consists in responding to the problem of post-implantation capsular contracture by attacking the hydrophobic / hydrophobic interaction between the surface of the prosthesis, which in the prior art is generally a hydrophobic surface, and potentially colonizing bacteria, also hydrophobic. If one disrupts the ability of the outer surface to become a substrate or a support for bacterial growth, then the bacterium will not be able to attach to this surface or produce a bio-protective film, with the adverse consequences induced described above. If the bacterium remains in a hydrophilic tissue and / or a hydrophilic fluid, then it will not be able to attach to the surface of the prosthesis, and the normal immune response of the host will "clean" the bacterium in a known manner. The invention therefore provides for making the prosthesis hydrophilic, made of elastomer, in particular silicone, to prevent any bacterial growth.

The preferred embodiment of the invention, which provides for chemically modifying the side and / or end groups of the silicone chain to make them more hydrophilic, will be described hereinafter in more detail. Preferably, basic silicone building blocks (or chains), which are normally hydrophobic, are chemically modified to render the molecule hydrophilic. This can be achieved by substituting the methyl groups along the silicone backbone by any group hydrophilic. Examples of these hydrophilic groups could be (but not limited to) alcohols, ionic groups, organic molecules, etc., used alone or in combination with each other. The substitution could be carried out at the end of the molecule, over the entire length of the molecule, or a combination of these two variants. The concentration of the substitution can be modified to alter the importance of hydrophilicity. Depending on which group is used for the substitution and the concentration, the hydrophilicity of the silicone could be limited to the surface where it extends through the entire silicone layer. Figure 1 is a cross-sectional view of a portion of a prosthesis 10 in which at least the outer surface 12 of the prosthesis is a silicone elastomer that is chemically modified to render the external surface hydrophilic. In this preferred embodiment of the invention, the silicone is modified from the outset to make it hydrophilic. After crosslinking, it is thus possible to form an implant that is hydrophilic from the start. However, modifying the surface of an already existing implant which is hydrophobic, as described in documents EP-0 057 033 and FR-2 822 383, requires the use of sophisticated and expensive means. The present invention makes it possible to obtain the desired hydrophilic properties in a simpler and less expensive manner.

The entire prosthesis can be made from the outset from hydrophilic silicone (or other suitable elastomer). Alternatively, the invention may also provide for making a hydrophobic silicone prosthesis blank, and then dipping this blank one or more times in a hydrophilic modified silicone, to form one or more hydrophilic outer layers. After baking or crosslinking, the resulting prosthesis will have a hydrophobic internal support structure, and a hydrophilic external surface. Here too, there is no treatment of the external surface of an implant previously made of hydrophobic silicone, but on the contrary, the external surface of the prosthesis is directly made of hydrophilic material during the manufacturing process of the prosthesis. Various variants that can be used in addition will be described below. These variants may include treatments of the surface of the implant, to further improve the hydrophilic properties of said surface. They may also include the use of a bactericidal and / or bacteriostatic material, in particular silver, especially in ionic form, which will have a non-toxic antimicrobial effect and which can therefore be used to kill or eliminate the bacterium if the one It must still develop on the surface of the prosthesis. This antimicrobial material may be embedded in or on the surface of the prosthesis and may, of course, be used in conjunction with hydrophilic surface properties of the prosthesis as mentioned above.

Hereinafter, various alternative embodiments will be described in more detail.

1.- Chemical modification of the external surface of a prosthesis.

While the outer surface of a prosthesis may include a wide variety of biocompatible elastomers, silicone is the most widely used elastomer for implantable soft tissue prostheses. Consequently, the modification of the external surface of a silicone prosthesis will be described by way of non-limiting example. The external surface of a silicone implant according to the invention can be made even more hydrophilic by covalently attaching it to a hydrophilic end group, especially at the end of the manufacturing process, by putting the external surface in contact with a reagent, such as, for example, cyanogen bromide. These types of agents activate the molecule to covalently link it to other molecules, thus fixing molecules preferably over an area in which they were not previously existing. In this way hydrophilic molecules can be covalently attached to the surface of the implant, making it even more hydrophilic. Alternatively, a hydrophobic end group may be covalently attached to the silicone surface, and subsequently separated, either chemically biologically, to render the surface hydrophilic. Still another method for rendering the outer surface of a silicone implant hydrophilic is to coat the silicone outer surface of the implant with silicone comprising monomers having both a hydrophobic end group and an end group opposite hydrophilic, to form the outermost layer. This "bipolar" silicone could be hydrophobically bonded to the silicone outer surface of the implant, leaving the opposing hydrophilic group exposed to the environment. Alternatively, the surface of the silicone implant may be coated with a hydrophobic-hydrophilic micelle.

2.- Hydrophilic particulate coating

Fig. 2 is a cross-sectional view of a portion of a prosthesis 20 having a plurality of biocompatible hydrophilic particles 21 partially embedded in the outer surface 22. Such a prosthesis can be made by several manufacturing methods. A preferred method comprises the steps of forming a silicone shell by repeatedly dipping a prosthesis mandrel into a silicone dispersion, whereby the coating formed between the dives is fired. After the final layer of the silicone elastomer is formed on the outer surface and the shell is of desired thickness, a coating of solid microparticles of a biocompatible hydrophilic material is applied to the surface before the outermost layer is completely cooked. The biocompatible hydrophilic material may be hydrophilic throughout the entire microparticle or only on the surface of said microparticle. After the microparticles have been applied to the uncured surface, the silicone is completely cooked (for example by heating), so that an embedded portion of the microparticles is embedded in the fired outer layer of silicone and an exposed portion of the microparticles. extends outward from the silicone surface. The prosthesis thus formed can be implanted in the body of a person. 3.- Coating of a silicone implant with a biocompatible hydrophilic material

It is known that certain hydrophilic biopolymers, such as collagen and hyaluronic acid, and synthetic hydrophilic polymers such as polyvinylpyrrolidone, which have a molecular weight less than

50,000 AMU (Atomic Mass Unit), are tolerated by the body, metabolized and / or excreted. Accordingly, a silicone film-wrapped implant comprising such polymers will have a hydrophilic outer surface. Figure 3 is a cross-sectional view of a portion of a prosthesis 30 having a hydrophilic layer or film 31 coated on the outer surface 32 of the implant. Such biocompatible hydrophilic film 31 may be attached to either a smooth surface or a textured surface of a silicone implant.

4.- Use of hydrophilic compounds non-covalently bound around the implant

Any solution, cream, compound, material, gel, that is reabsorbable in the body and that can interfere with the ability of a hydrophobic-hydrophobic interaction, can be used at the time of surgery to modify, break or interrupt the hydrophobic interaction -hydrophobe. This may for example include (but not limited to) lubricating materials for implant insertion, anti-adhesion materials, betadine, etc. These materials can be added directly to the implant pocket, on the surface of the implant itself, or a combination of both.

5.- Use of silver or silver-containing compounds or nanoparticles to interfere with the growth of bacteria in or on an implant Silver is well known to be a metal with therapeutic and low-toxicity capabilities. man. It can be bactericidal and / or bacteriostatic. Money or compounds containing money or silver nanoparticles, especially in ionic form, could be incorporated in the silicone or embedded in the surface of the prosthesis. Silver in any form can be used in conjunction with a previously mentioned hydrophilic external surface, or alone.

Although the present invention has been described with reference to several variants, it is understood that a person skilled in the art can make any useful modification without departing from the scope of the present invention as defined by the appended claims.

Claims

claims

1.- Surgical prosthesis (10; 20; 30) intended to be implanted in a body for plastic reconstitution, said prosthesis (10; 20; 30) being in contact with tissues of the body, characterized in that said prosthesis (10; 20; 30) has an outer surface (12; 22; 32) which is hydrophilic to at least partially prevent the attachment and / or development of bacteria, especially hydrophobic type, on said outer surface (12; 22; 32) .

2. The prosthesis according to claim 1, wherein said prosthesis (10; 20; 30) is made of elastomer, in particular silicone, said elastomer being modified and rendered hydrophilic before manufacture of said prosthesis.

The prosthesis of claim 2, wherein said outer surface (22) further comprises a plurality of biocompatible hydrophilic microparticles (21) partially embedded in the hydrophilic elastomer.

4. The prosthesis according to claim 2 or 3, wherein said outer surface (12) is made even more hydrophilic by a modification of silica contained in said outer surface.

5. The prosthesis according to any one of claims 2 to 4, wherein hydrophilic end groups are attached to the silicone by a covalent bond.

The prosthesis of any one of claims 2 to 5, wherein said outer surface (32) comprises a coating (31) of a biocompatible hydrophilic film.

The prosthesis of any one of claims 2 to 6, wherein said outer surface (32) is coated with a hydrophilic organic substance (31) in a covalent or ionic manner.

8. Prosthesis according to any one of the preceding claims, wherein the outer surface of the prosthesis is coated with and / or contains a bactericidal material and / or bacteriostatic to eliminate and / or prevent the growth and / or metabolism of bacterial contamination around, on and / or in said prosthesis.

The prosthesis of claim 8, wherein said bactericidal and / or bacteriostatic material comprises silver, silver compounds or silver nano-particles, or alloys comprising such material.

The method of manufacturing a prosthesis according to any one of the preceding claims, comprising the steps of providing an elastomer, such as silicone, modifying said elastomer to render it hydrophilic, and using said modified elastomer to manufacture an at least partially hydrophilic prosthesis.

11. The method of claim 10, wherein a hydrophobic elastomer prosthesis blank is dipped, preferably several times, in a hydrophilic modified elastomer, and then crosslinked, to produce a prosthesis having a hydrophobic internal support and a hydrophilic outer surface. .

The method of claim 10 or 11, wherein the step of modifying the elastomer is performed chemically by substituting the methyl groups of the elastomer molecules with hydrophilic groups.