Silicone breast implant with reinforcing fibers

Abstract

Subject of the invention is a medical implant comprising a fiber reinforced silicone comprising (A) a silicone matrix and (B) fibers embedded in the silicone matrix, wherein the fibers comprise a comb polymer having a base polymer and side chains, wherein the base polymer is an organic polymer and the side chains comprise polysiloxanes. The invention also relates to outer shells of breast implants and uses and methods.

Claims

1. An outer shell of a breast implant, wherein the outer shell comprises a fiber reinforced silicone comprising (A) a silicone matrix and (B) fibers embedded in the silicone matrix, wherein the fibers comprise a comb polymer having a base polymer and side chains, wherein the base polymer is an organic polymer and the side chains comprise polysiloxanes.

2. The outer shell of a breast implant according to claim 1, wherein the polysiloxane side chains are linked to the base polymer via ester bonds, amide bonds or ether bonds.

3. The outer shell of a breast implant according to claim 1, wherein the comb polymer comprises a) at least one structural unit A ##STR00004## wherein R.sup.1 independently of one another represents H or CH.sub.3; R.sup.2 independently of one another represents an ester group COO, an amide group CONH, an ether group O or no group (void), R.sup.3 independently of one another represents R.sup.7Y, wherein R.sup.7 is a C.sub.1-C.sub.6 alkylene group, and Y is either no group (void) or O, R.sup.4 independently of one another represents C.sub.1-C.sub.4 alkyl, R.sup.5 independently of one another represents C.sub.1-C.sub.18 alkyl, n independently of one another is a value between 5 and 2000, and b) at least one structural unit B ##STR00005## wherein R.sup.1 independently of one another represents H or CH.sub.3; R.sup.2 independently of one another represents H or CH.sub.3, R.sup.3 independently of one another represents H or CH.sub.3, R.sup.4 independently of one another represents H, CN, COOR.sup.6, OR.sup.6, CONR.sup.6 or R.sup.6, wherein R.sup.6 is C.sub.1-C.sub.8 alkyl.

4. The outer shell of a breast implant according to claim 1, wherein the fibers are electrospun.

5. The outer shell of a breast implant according to claim 1, wherein the fibers are oriented.

6. The outer shell of a breast implant according to claim 5, wherein at least a portion of the oriented fibers cross the equatorial region and/or equatorial plane of the implant.

7. The outer shell of a breast implant according to claim 1, wherein the surface of the fiber reinforced silicone is textured.

8. The outer shell of a breast implant according to claim 1, wherein the fiber reinforced silicone is a laminate comprising at least two layers of fibers.

9. A breast implant comprising an outer shell of claim 1 and a core.

10. A method for producing an outer shell of claim 1, wherein production of the fiber reinforced silicone comprises dip coating and/or electrospinning.

11. A method for producing an outer shell of claim 1, comprising the steps of: (a) providing a support and a solution of the comb polymer, (b) spinning the solution to obtain fibers of the polymer, (c) depositing fibers of the comb polymer on the support, (d) impregnating the fibers with a liquid silicone, (e) curing the product of step (d), thereby obtaining a fiber reinforced silicone, and (f) optionally repeating steps (a) to (e) at least once, whereby the fiber reinforced silicone obtained in step (e) is used as the support.

12. The method of claim 10, wherein the fibers are oriented by electrospinning by an electrode in the support.

13. A method for producing a breast implant or the outer shell of a breast implant, which comprises including in a breast implant or an outer shell of a breast implant a fiber reinforced silicone, wherein the fiber reinforced silicone comprises (A) a silicone matrix and (B) fibers embedded in the silicone matrix, wherein the fibers comprise a comb polymer having a base polymer and side chains, wherein the base polymer is an organic polymer and the side chains comprise polysiloxane.

14. A method which comprises implanting a breast implant in a female human, wherein the breast implant comprises a fiber reinforced silicone, wherein the fiber reinforced silicone comprises (A) a silicone matrix and (B) fibers embedded in the silicone matrix, wherein the fibers comprise a comb polymer having a base polymer and side chains, wherein the base polymer is an organic polymer and the side chains comprise polysiloxane.

15. A method which comprises implanting a breast implant in a human female, wherein the breast implant comprises an outer shell of claim 1.

16. The outer shell of a breast implant according to claim 3, wherein: in the at least one structural unit A, R.sup.7 is methylene, ethylene or propylene, R.sup.4 independently of one another represents methyl or ethyl, R.sup.5 independently of one another represents C.sub.1-C.sub.6 alkyl, n independently of one another is a value between 20 and 1000, and in the at least one structural unit B, R.sup.2 represents H, R.sup.3 represents H, R.sup.6 is methyl or ethyl.

17. The outer shell of a breast implant according to claim 7, wherein the texture is obtained in a process comprising modifying the surface with fractionated crystals, and/or wherein the surface roughness R.sub.Z is in the range from 10 m to 150 m, and/or wherein the average lateral distance (median (dx)) between indentations on the surface is between 45 m and 210 m.

18. A method for producing an outer shell of claim 11, which comprises in step (b), spinning the solution to obtain fibers of the polymer by electrospinning, and in step (d), impregnating the fibers with a liquid silicone by dip coating.

19. The method of claim 14, wherein the method comprises breast reconstruction and/or breast augmentation.

20. The method of claim 15, wherein the method comprises breast reconstruction and/or breast augmentation.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1 to 4 show schematically and in exemplified form how a support can be coated with silicone in a method of the invention.

(2) FIG. 5 shows schematically and in exemplified form an electro-spinning device for depositing fibers on a coated support.

(3) FIG. 6 shows schematically and in exemplified form a device of FIG. 5, in which a circular electrode is positioned in the support.

(4) FIGS. 7a and 7b show schematically and in exemplified form designs of circular electrodes in the support. FIG. 7a shows an embodiment of circular electrodes for obtaining fiber orientation as parallel disks. FIG. 7b shows an embodiment of circular electrodes for obtaining fiber orientation as rings with connections to the center electrode contact.

(5) FIG. 8 shows in graphical form the correlation between Weibull modulus m and normalized strength .sub.0 of various breast implants of the state of the art and an inventive implant. Where appropriate, the texture of the implant is specified in micrometers. The values are indicated for commercially available implants of Poly Implant Prothese (PIP) microtextured (white circles) and textured (black circles); a commercially available non-PIP standard implant (black rhombus), a series of textured silicone implants produced according to example without nanofibers with different average distances between indentations (white squares), and untextured silicone implants without and with nanofibers (black squares, the effect of nanofibers and increase of stability is demonstrated by the arrow).

(6) FIG. 9 shows the influence of mesh size on stress and strain at break as determined in example 9. One data point represents median and IQR from about 90 tensile specimen of a thickness between 0.50 mm and 1.00 mm, which is typical for commercial implants as shown in Daenicke, 2012. The open squares relate to strain at break and the black squares to stress at break.

(7) FIG. 10 shows a textured surface of a silicone implant obtained with fractionated crystals having a size below 63 m according to example 6.

EXAMPLES

(8) 1. Preparation of Salt for Texturing

(9) For later texturing, six particle size fractions were isolated from the commercial kitchen salt (trademark Zals, Eurovera Ltd. & KG). The salt was fractionated by consecutive sieving operations using 5 tests sieves with an aperture size of 500, 250, 150, 100 and 63 m on an As200 test sieve shaker (Retsch GmbH). The sieves fulfil ISO 3310 and ASTM E11 (according to Retsch GmbH, 2015). Three ceramic balls were added to each sieve and the salt was treated at an amplitude of 2.5 mm for 8 min. Thereby, crystal fractions were obtained comprising crystals of about <63 m (up to >0 m), >63 m (up to 100 m), >100 m (up to 150 m), >150 m (up to 250 m) and >250 m (up to 500 m) and >500 m.

(10) 2. Creating of a Curable Liquid Silicone Rubber (LSR) Blend for Mould Filling

(11) The liquid silicone rubber (trademark Elastosil LR 3003/30, available from Wacker Chemie AG, DE) has a high tear strength and exceeds the required 450% minimum strain at break for mammary implants according to ISO 14607:2009. Additionally it has the same Shore Hardness (Type A) and a similar tear strength as addition cured silicone dispersion available under the trademark MED-6400 of NuSil Technology LLC, US, used for manufacturing of mammary implant shells by the former company Poly Implant Prothse. Components A and B of Elastosil LR 3003/30 were weighted in ratio 1:1 and mixed at 1000 rpm for 5 min by a SAC 150 SP speed mixer (Hauschild & Co. KG). The ratio of 1:1 was kept with a resolution of 1 mass %.

(12) 3. Removing Dispersed Air for Better Mechanical and Surface Properties

(13) The curable LSR blend is exposed to an under pressure of 0.4 mbar in a desiccator for 20 min. This was followed by mixing the blend for another 5 min at 1000 rpm and evacuating for 15 min at 0.4 mbar. Air removal is important, because otherwise the mechanical values such as .sub.0 and m can be decreased.

(14) 4. Mould Filling and Preparation of a Homogeneous LSR Surface for Texturing

(15) LSR specimen for texturing can be produced similar to commercial breast implants using the dip coating process. At a withdrawal speed of e.g. 2.5 mm/s a layer thickness of 1.81+/0.30 mm was achieved. Other thicknesses can be manufactured by adapting the viscosity and/or the withdrawal speed. The desired thickness should be manufactured under adaption of the withdrawal speed if the desired recipe remains unmodified. The thickness can be adjusted according to the equation (thicknessviscosity.sup.n velocity.sup.m), wherein n and m are in the range between 0.5 and 0.7 (mostly 0.5) and in most cases n=m. For achieving a greater volume, LSR test stripes of a thickness of 0.50 mm; 0.75 mm and 1.00 mm were made by casting the curable blend into a milled PTFE trough mould. The casting was fastened by spreading the LSR with a doctor blade. At first the material was spread in greater thickness than the final stripe. Then dispersed air is drawn to the surface through under pressure of 0.4 mbar for 15 min. In a second step the bubble containing surplus of LSR at the surface was removed with a doctor blade. Thereby the withdrawal speed of the doctor blade was 5+/2.5 mm/s. If 10 min at 0.4 mbar caused yet again air bubbles at the surface, more LSR was added and the casting procedure was repeated.

(16) 5. Preparation of Composite

(17) For preparation of a composite, electrospun fibers from poly(methyl methacrylate)-graft-poly(dimethyl siloxane) copolymer (PMMA-g-PDMS) were used which had been prepared according to the process described in Swart et al., 2010 (see section experimental, copolymer synthesis and electrospinning procedure). A silicone composite was prepared in line with Swart et al, 2010 (experimental, composite preparation) with an LSR blend as in examples 2 to 4 above. In brief, a thin layer of the uncured LSR was evenly spread on a piece of non-stick Teflon surface. This layer was subjected to vacuum to remove any air bubbles remaining from the mixing of silicone oligomers with catalyst. A pre-cut piece of nanofiber mat was gently placed on top of the silicone layer and completely wetted. The system was repeatedly placed under vacuum to remove air. Additional silicone was placed on top of the fiber mat to ensure complete coverage of the fibers and uniform wetting. The system was placed in an air ventilated oven and allowed to cure for 20 h at 120 C.

(18) 6. Texturing

(19) The surfaces of homogeneous LSR prepared according to the examples above were textured with salt crystal fractions obtained by sieving according to example 1. From a height of 4+/3 cm, a salt fraction prepared was trickled on the prepared surface and then distributed by tilting and shaking. Particle impact and weight as well as surface tension and deformation were responsible for the degree of particle sinking in. For shells manufactured by dip coating the outer (last) layer is additionally brought in contact with salt or sugar or other soluble substances, preferably water soluble solid substances. Therefore it is possible in a subsequent step to wash out the above describe salt, sugar or other dissolvable substance to achieve a desired surface structure. The applied solvent should not dissolve or substantially swell the LSR material. The specimens were cured at typically 120 C. for up to 20 h. After cooling down to room temperature, the salt was removed by running tap water for 4 min. A textured surface obtained with fractionated crystals having a size below 63 m is shown in FIG. 10. By this process, surface structures very similar to those of commercial silicone breast implants could be created at a comparable thickness. However, a fractionation of salt with respect to grain size enables deliberate textures.

(20) 7. Surface Roughness of Textured Products

(21) The mean surface roughness R.sub.z was determined according to DIN ISO 4287 for a series of textured silicone products obtained according to the examples above without reinforcing fibers. To achieve comparable information about the dimensions of the surface texture generated, the surface roughness was investigated. According to DIN EN ISO 4287 the mean surface roughness R.sub.z was determined. Therefore images of the textured surface were taken with a 3D laser scanning microscope (Keyance VK-9700). For determination of the R.sub.z values, the sampling length and the filter parameters were selected according DIN EN ISO 4288 and DIN EN ISO 3274, respectively. The results with mean values and standard deviation of the six surface textures are summarized in table 1 below. The mean value and standard deviation was obtained from five measurements each. The results demonstrate that a large variety of R.sub.z values is accessible by texturing silicone implants with salt fractions according to the above described procedure.

(22) TABLE-US-00001 TABLE 1 Mean surface roughness R.sub.z according to DIN ISO 4287 of six surfaces textured with salt fractions Texture [m] R.sub.z (m) >500 623.05 57.02 >250 508.74 62.21 >150 146.50 4.19 >100 172.45 1.82 >63 123.83 5.51 <63 24.80 0.85

(23) Further, the average lateral distance (medium (dx)) between indentations on the surface was determined graphically from microscopic images of cross sectional samples. A baseline x was defined parallel to the surface with a y coordinate perpendicular to the surface. The lowest positions in all indentations are marked on the x baseline. Distances dx between adjacent indentations on the x axis were calculated. The median (dx) was determined as 420.9 m for the >500 m sample, 283.9 m for the >250 m sample, 211.1 m for the >150 m sample, 149.4 m for the >100 m sample, 75.3 m for the >63 m sample and 47.7 m for the <63 m sample.

(24) 8. Influencing Mechanical Properties by Varying Size of Salt Particles Used for Texturing

(25) The mechanical properties were determined by tensile testing. Three stripes textured with salt particles of each fraction were produced according to the examples above, but without incorporation of fibers. This was done for each of the thicknesses 0.50 mm, 0.75 mm and 1.00 mm. Ten dumbbell specimens shaped according to DIN 53504 type S3 were punched out of each stripe. They were tested in a Zwick/Roell Frank-811110 universal testing machine according to DIN 53504, but with an elongation speed of 20 mm/min instead of 200 mm/min. As a measure for the size of the salt particles the mesh width is used in the following. The effect of varying the mesh size on stress at break and strain at break is shown in FIG. 9. By reducing the mesh size from 500 m to 63 m the median of stress at break could be increased by more than 85% from 2.17 MPa (IQR: 0.58 MPa) to 4.04 MPa (IQR: 0.52 MPa). The median of strain at break at the same time could be raise by over 30% from 656.56% (IQR: 81.96%) to 865.57% (IQR: 149.41%). Reducing the size of the salt particles by using sieves with smaller mesh size improves the stress at break and the strain at break simultaneously. Smaller particles cause smaller indentions on the surface and thereby cause lesser deterioration of the mechanical properties. In addition, it was found that thicker silicone layers while using the same particles for texturing increase the mechanical properties by increasing the portion of not deteriorated material (data not shown). Overall, the data demonstrates that fine microstructures provided with fine sieved crystals can significantly enhance the mechanical stability of silicone implants.

(26) 9. Resilience of the Products

(27) The resilience of products obtained as described above was examined by determining parameters .sub.0 and m and graphical evaluation in a Weibull plot according to the method described in Schubert et al., 2013. The results and values for conventional silicone implants are summarized in FIG. 8. A series of textured silicone stripes without nanofibers was examined, wherein the average depths of indentations and average distances between indentations were decreased by applying smaller sized salt fractions from >500 m to <63 m according to example 6 above. The open squares in FIG. 8 indicate the general improvement of resilience by modifying the implant shell structure from rough to smaller microstructures to smooth. Further, silicone stripes were prepared according to the examples with and without nanofibers (FIG. 8, black squares). The shift along the arrow demonstrates the improvement by adding the fibers. Overall, the results show that by inclusion of fibers into the silicone matrix, the stability parameters can be shifted into a region which is highly advantageous for use of breast implants and long-term stability. A fine microstructure can impart additional stability to the implant.

LITERATURE

(28) Bayley et al., Large strain and toughness enhancement of poly(dimethyl siloxane) composite films filled with electrospun polyacrylonitril-graft-poly(dimethyl siloxane) fibers and multi-walled carbon nanotubes, 2011, Polymer 52, 4061-4072 Colas and Curtis, Silicone biomaterials: history and chemistry & medical applications of silicones, 2005, from An introduction to materials in medicine, Biomaterials Science, 2.sup.nd edition, editor: Ratner et al., Elsevier, Inc. Daenicke, Jonas, Kartierung and Untersuchung der mechanischen Eigenschaften von Silicon-Brustimplantathllen, Bachelor Thesis, 2012, Friedrich-Alexander-Universitt Erlangen Nrnberg Daniels, Silicone breast implant materials, 2012, Swiss Medical Weekly, 142:w13614 RETSCH GMBH, Sieve AnalysisTaking a Close Look at QualityAn Expert Guide to Particle Size Analysis, 2015, http://www.retsch.com/dltmp/www/53e4b562-5294-4711-9111-636500000000-c5e17882ae92/expert_guide_sieving_en.pdf, Accessed 23 Sep. 2015 Schubert et al., On the failure of silicone breast implants: new insights by mapping the mechanical properties of implant shells, 2013, Polymer International, DOI 10.1002/pi.4619 Swart et al., Organic-inorganic hybrid copolymer fibers and their use in silicone laminate composites, 2010, Polymer Engineering and Science, DOI 10.1002/pen

LIST OF REFERENCE SIGNS

(29) 1 support 2 container 3 silicone bath 4 silicone coating 5 fibers 6 electrospinning device 7 syringe 8 pump 9 needle 10 voltage source 11 connection 12 direction 13 double ring type collector electrode