Device to be implanted in a subject's body to form an implant, and associated tissue mass and method

Abstract

A device to be implanted in a subject's body to form an implant for replacing and/or increasing a volume of soft tissue, the device being of the type including a three-dimensional frame which defines an inner space in the frame. The frame is typically bio-absorbable and includes two side apertures forming a transverse passage for inserting a vascular pedicle. The device further has at least two bio-absorbable textile sheets that can be stacked on each other in the inner space of the frame.

Claims

1. A device adapted to be implanted in the body of a subject to form an implant capable of replacing and/or increasing a soft tissue volume, said device being of the type comprising a three-dimensional wireframe which defines a space internal to said wireframe, wherein said wireframe is bioresorbable, comprises two lateral openings forming a transverse passage enabling the insertion of a vascular pedicle and further comprises at least two sheets of a bioresorbable textile adapted to be stacked one on top of the other in said space internal to said wireframe, and wherein said textile is a three-dimensional structure which includes at least two superimposed surface layers, each layer being a respective face of two opposite faces of said textile, and both layers being formed by an interweaving of at least two same strands connecting and defining said surface layers, said interwoven strands form pores which pass throughout the thickness of said textile; and wherein said textile includes connection points between said surface layers, said connection points corresponding to nodes or fastening areas between said strands, and being distributed so that said surface layers may be separated in the direction of the thickness of the textile over at least 30% of the surface of the textile.

2. The device according to claim 1, wherein said wireframe includes a wall which defines an edge and a plurality of perforations distributed over said wall and/or an open portion formed in said wall and extending above said edge of said wireframe, said open portion extending from the apex of the dome when said wireframe is substantially dome-like shaped.

3. The device according to claim 1, wherein said wireframe includes assembled arches whose free ends are located in the same plane and at least a first group of outer arches and a second group of inner arches, located in the space defined by said outer arches, the free ends of said arches of said first and second groups form feet being located in the same plane, and the feet of the outer arches rest on a first sheet of said at least two sheets of bioresorbable textile, and the feet of the inner arches pass throughout a second sheet of said at least two sheets of bioresorbable textile, said second sheet being disposed above said first sheet.

4. The device according to claim 1, wherein the connection points are distributed so that said surface layers may be separated in the direction of the thickness of the textile over at least 50% of the surface of the textile.

5. The device according to claim 4, wherein said textile further includes at least one interlayer disposed between said surface layers and formed with interwoven threads, said interwoven threads of said surface layer and said interlayer form apertures.

6. The device according to claim 4, wherein said textile includes pores with dispersed diameters, the arithmetic mean of the diameter of said pores is substantially equal to or smaller than 3.5 mm and substantially equal to or larger than 1.5 mm and 75% of said pores have a diameter substantially equal to or larger than 2 mm and substantially equal to or smaller than 3.5 mm.

7. The device according to claim 4, wherein said textile has a deformation at break-up in the machine direction and/or in the cross-machine direction lower than 50%.

8. The device according to claim 4, wherein said textile is formed by at least two threads of different diameters and the ratio of the diameters of the threads is comprised between 2 and 3.

9. The device according to claim 4, wherein said textile has an air permeability higher than or equal to 10000 L/m.sup.2/s and a thickness larger than or equal to 0.50 mm.

10. The device according to claim 1, further comprising a layer of cells selected from adipocytes located between the two textile sheets, the cells being capable of differentiating into adipocytes and mixtures of these two types of cells and said stacking is housed in said wireframe and fills it at least partially.

11. The device according to claim 5, wherein apertures of said interlayer do not match with said apertures of said surface layers of said textile.

12. The device according to claim 4, wherein said textile includes pores with dispersed diameters, the arithmetic mean of the diameter of said pores is substantially equal to 2 mm.

13. A device adapted to be implanted in the body of a subject to form an implant capable of replacing and/or increasing a soft tissue volume, said device being of the type comprising a three-dimensional wireframe which defines a space internal to said wireframe, wherein said wireframe is bioresorbable, comprises two lateral openings forming a transverse passage enabling the insertion of a vascular pedicle and further comprises at least two sheets of a bioresorbable textile adapted to be stacked one on top of the other in said space internal to said wireframe, wherein said wireframe includes assembled arches whose free ends are located in the same plane and at least a first group of outer arches and a second group of inner arches, located in the space defined by said outer arches, the free ends of said arches of said first and second groups form feet being located in the same plane, and the feet of the outer arches rest on a first sheet of said at least two sheets of bioresorbable textile, and the feet of the inner arches pass throughout a second sheet of said at least two sheets of bioresorbable textile, said second sheet being disposed above said first sheet.

Description

FIGURES

(1) The present invention, its features and the various advantages provided thereby will better appear and will be better understood upon reading the following description of three particular embodiments of the present invention, presented as non-limiting illustrative examples with reference to the drawings in which:

(2) FIGS. 1a and 1b schematically represent perspective views of two embodiments of the wireframe of the device of the invention;

(3) FIG. 2 represents a schematic view of a cross-section of a particular third embodiment of the device of the invention ready for its implantation in the body of a subject;

(4) FIG. 3A to 3C represent photographs taken with an optical microscope of the different textiles used for the manufacture of the sheets equipping the device of the invention and referenced from A to C;

(5) FIG. 4 represents a photograph of the tissue masses obtained respectively with sheets of the textile A, to the left and to the right with sheets of the textile B;

(6) FIG. 5 represents a photograph showing to the left a tissue mass obtained with the textile A in an aqueous solution tube and to the right, a tissue mass obtained with the textile B also plunged in a tube containing an aqueous solution;

(7) FIG. 6 represents a photograph showing the aspect of the mass obtained with disks of the textile A (to the left) and that of the mass obtained with disks of the textile B (to the right), after 24 h in a physiologic serum;

(8) FIG. 7 represents a photograph showing a cross-section of the mass obtained with disks of the textile A, made with the scalpel and, a cross-section of the tissue mass obtained with disks of the textile B;

(9) FIG. 8 represents a photograph of the aspect of each of the tissue masses after peel-off of a sheet, the photograph to the top concerns the mass obtained with sheets of the textile A and that to the bottom, the mass obtained with sheets of the textile B;

(10) FIG. 9 represents a photograph obtained with an optical microscope of a sheet of the textile A (to the top) and of a sheet of the textile B on which a supernatant has been deposited as explained later on;

(11) FIG. 10 represents a fourth embodiment of the wireframe of the device of the invention; and

(12) FIG. 11 represents diagrams of the dispersion of the size of the pores for each of Samples A to C.

(13) Referring to FIG. 1a, a first embodiment of the wireframe of the device of the invention will be described. The wireframe 1 includes a wall 11 which defines a lower edge 13. The wall 11 includes a plurality of perforations 15 and two lateral openings 17 and 19 which perforate the wall 11 and are located substantially opposite each other so as to define a passage transverse to the wireframe 1. The openings 17 and 19 are located above the lower edge 13.

(14) The second embodiment will now be described with reference to FIG. 1b; the elements in common with the first embodiment are referenced identically. The wall 11 of the wireframe includes an open portion 16 located above the open bottom of the wireframe 1. This open portion forms an upper edge 18. The wall also includes two indentations 21 and 23 which cut the lower edge 13 and form openings in the wall 11 above the lower edge 13. These two indentations 21 and 23 form a passage which passes throughout the wireframe 1.

(15) A third embodiment of the device of the invention will now be described with reference to FIG. 2. The elements in common with the aforementioned two embodiments are referenced identically.

(16) The wireframe 1 includes a wall 11 which has a plurality of perforations 15 and two indentations 21 and 23. The wireframe comprises a stacking 3 which is formed by superimposed textile sheets 31 (in black) and layers of adipocytes 33 (in white) or fatty tissue. The stacking 3 comprises a through passage 35 formed by incision for example. The openings of this passage 35 correspond to the indentations 21 and 23. It is thus possible by introducing a suitable tool through one of the indentations 21 and 23 and by hooking it to a vascular pedicle, to introduce this pedicle into the passage 35 and to deposit it, for example, substantially at the center of the latter.

(17) A fourth embodiment of the wireframe will now be described with reference to FIG. 10.

(18) In this particular embodiment, the wireframe 1 includes three series of arches 30, 50 and 70. The arches of the first series 30 form 6 feet which correspond to the ends 310 of the arches and which rest on a first textile sheet 61. These arches form a first dome. Inside this dome, lies the second series of arches 50 which includes 6 feet 510 which correspond to the free ends of the arches and which rest on the first sheet 61. The arches of the second series 50 pass throughout a second sheet 63 which is disposed above the first sheet 61. The second sheet 63 has a smaller surface area than the first sheet 61. The arches of the second series 50 pass throughout the second sheet 63 either at the level of its pores, or at the level of openings formed in the latter. The third series of arches 70 is located inside the volume delimited by the arches 5. The arches 70 include 6 feet 710 which correspond to the free ends of the arches 70 and which rest on the first sheet 61. The arches 70 pass throughout a third sheet 65 with a smaller surface area than that of the first and second sheets. Such a wireframe allows defining, with minimum material, a chamber which allows blocking the stacking of the sheets and promotes the cellular growth when cells are deposited on the sheets. Hence, it is easily resorbable in the organism of a subject and allows easy formation of the stacking by simple drilling of the sheets with the arches 30, 50 or 70. The arches naturally define openings which form a through passage enabling the insertion of the pedicle into the three-dimensional structure.

EXAMPLES

(19) Several textiles have been studied with reference to the formation of the stacking which also forms the tissue mass of the invention.

(20) Characterization of the Textiles

(21) Three samples of different textiles, referenced from A to C, have been studied. Each of these textiles has been obtained by interweaving of two threads. All textiles include connection points which in this case consist of nodes. For each of the samples, we have measured the grammage, the thickness, the air permeability and the diameter of the threads. The porosity has been calculated as aforementioned.

(22) The measurement of the grammage (g/m.sup.2) has been implemented according to standard ISO 3374. Three samples of each textile sample referenced A to C have been collected with a 14 cm diameter (100 cm.sup.2) circular die in order to obtain a good representativeness of the different textiles. Each of the samples is weighted and the grammage is calculated by dividing the measured mass by the surface area of the sample. Afterwards, the average and the standard deviation of the obtained grammages are calculated. All samples whose grammage is not comprised within the range [average−standard deviation; average+standard deviation] are removed and we start again collecting textile samples until obtaining five samples per reference textile comprised within the aforementioned grammage range. The weighing is performed with a Sartorius ENTRIS224i-1S scale.

(23) The air permeability is measured using an AP-36 VVC air permeability meter with a suction pressure drop fixed at 196 Pa according to standard AFNOR G07-111. The air permeability result is expressed in L/m.sup.2/s which represents an air flow rate relative to a 1 m.sup.2 surface area. The textile samples used for the measurement of permeability have a 20 cm.sup.2 surface area.

(24) The measurement of the thickness is carried out according to standard EN ISO 5084 on VVC 2000 apparatus with a used weight corresponding to a 1 kPa load, the unit of measurement is the millimeter. Once the grammage is measured and validated, these same samples are used for the measurement of the thickness of each of the textiles.

(25) The measurement of the diameter of the threads is implemented with an optical microscope. A cross-section of the thread is made using a razor blade and then the diameter of the single yarn(s) forming the thread is observed and measured using a binocular optical microscope (Axiolab Pol of Carl Zeiss).

(26) Table I below groups together the different parameters of each of the textiles.

(27) TABLE-US-00001 TABLE I A B C Grammage (g/m.sup.2) 84.41 129.00 108.78 Thickness (mm) 0.84 0.94 0.77 Porosity (%) 91.31 88.17 87.88 Thread diameter (μm) 80.07 119.52 81.75 Air permeability (L/m.sup.2/s) 10960.00 9042.00 8702.00

(28) Moreover, photographs taken with the microscope of each of the samples have also been made. These photographs are shown in FIG. 3A to 3C.

(29) Referring to FIG. 3A to 3C, we notice that Sample A has three superimposed layers of threads, the layers do not mesh into each other. Sample A is obtained by interweaving two threads with different diameters, in this instance a 49 dtx thread with a 120 dtx thread. Sample A includes apertures with different sizes and no compact area formed by side-by-side threads is likely to create an area devoid of apertures. The apertures of one layer do not match with those of the two other ones but the textile includes pores which are formed by the areas where the apertures of the three layers coincide. We also notice that the nodes are sufficiently away from each other so as to enable the layers of threads to locally separate from each other in the direction of the thickness of the textile.

(30) Sample B does not include a thickness formed by an interweaving of two threads of different diameters. Moreover, Sample B has a denser localized area which includes no or only very tiny apertures (see the top left of Photograph B).

(31) Sample C has two layers of threads of different diameters. The size of the apertures is not homogeneous. Sample C is formed by an interweaving of two threads of different diameters. Most of the pores is formed by apertures of the two layers which coincide. The two layers are close to each other because of the large number of nodes; locally it seems that there is only but one single layer of threads (see the area to the left where the pores have a larger size). Sample C includes an area where the interwoven threads form a continuous threads surface without any pores (see the bottom left of FIG. 3C).

(32) Study of the Mechanical Properties of the Textiles

(33) Table II below groups together the results obtained during the tensile tests on the aforementioned textiles A to C.

(34) TABLE-US-00002 TABLE II A_cross- C_cross- Sample A_machine machine B C_machine machine Number of 4/5 3/4 2/4 4/5 5/5 considered test pieces Maximum 32.04 57.13 67.85 53.31 91.08 deformation (%) Deformation 32.68 57.54 70.62 53.56 93.72 at break-up (%) Maximum force (N) 70.53 153.67 187.60 87.53 233.58 Force at 66.65 143.20 174.50 83.60 216.98 break-up (N) Maximum stress 0.71 1.54 1.88 0.88 2.34 (Mpa) Elastic modulus 5.87 6.72 5.92 2.87 4.77 (Mpa)

(35) The term «maximum deformation» refers to the maximum deformation obtained before break-up. The term «machine» indicates a tensile test in the machine direction. In light of the results of Table II, we notice that Sample A, in the machine direction, has the lowest values in terms of deformation, maximum force and force at break-up. Sample A, in the machine direction, is the least extendible of all, with only 32% of deformation at break-up and has an elastic modulus amongst the highest with 5.87 Mpa. Sample A, in the cross-machine direction, extends two times more than in the machine direction with a 57% elongation and has the highest elastic modulus. In general, Sample A is the least extendible of all samples while having the highest elastic modulus.

(36) Sample B presents intermediate mechanical characteristics between the cells of Samples A and C; it is more extendible than Sample A in both directions and less extendible than Sample C in the cross-machine direction. Sample B has an elastic modulus close to that of Sample A with 5.92 Mpa.

(37) Sample C, in the cross-machine direction, is the most extendible with 93% of deformation at break-up and the highest values for the maximum force and the force at break-up but its elastic modulus does not reach the value of that of Sample A with only 4.77 Mpa.

(38) Study of the Size of the Pores of the Samples

(39) We have used a profilometer which allows determining the roughness and the micro-geometry of a surface.

(40) The used profilometer is the AltiSurf 500 supplied by the manufacturer Altimet.

(41) The performed measurements do not follow any standard and are serve only a purely qualitative purpose.

(42) The dimensions of the samples are described in Table III below.

(43) TABLE-US-00003 TABLE III Sample A B C Dimensions of the sample 50 × 50 40 × 40 23 × 23 (mm × mm) Surface area (mm.sup.2) 2500 1600 529

(44) From the images obtained using the profilometer, the distribution of the size of the pores has been studied thanks to the software ImageJ. This software is an image analysis program developed by the National Institute of Mental Health Bethesda, Md., in the United States. The software allows calculating the surface area as a function of the pixels and of the scale imposed by the user. The images obtained thanks to the profilometer are transformed into 8-bit images, in gray shades. Afterwards, the «Binary» function has been used in order to transform the image in gray shades into an image in black and white. Once this step is completed, we proceed with the delimitation step with the «Threshold» function which allows segmenting the pores and the background. Finally, it is possible to use the «Analyze Particles» function in order to quantify the amount of pores as well as the respective surface area of each of these pores.

(45) It is possible to select the size of the pores that is taken into account in the analysis. All sizes have been taken into account. The pores that are located on the edges of the sample and which are not therefore delimited have not been taken into account, since their size cannot be determined.

(46) For the calculation of the surface area of the pores, we have considered that these pores were circles and then we have calculated the corresponding diameter.

(47) FIG. 11 represents diagrams of the distribution of the size of the pores. We have considered a 0.05 mm interval in order to have a quite fine distribution.

(48) On the basis of the results represented in FIG. 11, we notice that Sample A has a very heterogeneous distribution of the diameters of pores. This distribution defines the interval on which the samples will be compared. Indeed, the diameters of the pores vary from 0.087 to 7.225 mm. We notice that the small-sized pores are very numerous in comparison with the other samples. For Sample A, there are as many as 33 pores having a diameter comprised between 0.10 and 0.15.

(49) Sample B presents a distribution curve of the size of the pores which is approximately a Gauss curve.

(50) For Sample C, we observe a larger number of small-diameter pores.

(51) Table IV below groups together the different values of the different averages of the sizes of pores for each of the samples.

(52) TABLE-US-00004 TABLE IV Sample A B C Arithmetic mean (mm) 2.002 1.211 0.629 Geometric mean (mm) 1.129 1.135 0.453 Standard deviation (mm) 1.561 0.347 0.531 Variance (mm.sup.2) 2.436 0.121 0.282 Maximum (mm) 7.225 2.071 1.939 Minimum (mm) 0.087 0.118 0.107 Total number of members 277 171 102 Median (mm) 2.068 1.223 0.424 Quartile 1 (mm) 0.407 1.021 0.242 Quartile 2 (mm) 2.068 1.223 0.424 Quartile 3 (mm) 3.233 1.470 0.742

(53) The difference between the arithmetic and geometric means with reference to Sample A in comparison with the other samples is indicative of the heterogeneity of the distribution of the diameters of the pores. We also observe the highest standard deviation for Sample A among the four samples which shows the large dispersion of the diameters of the pores for Sample A. The standard deviation for Samples B and C being the lowest, it is possible to conclude that the values are centered around the arithmetic mean. Finally, the quartiles indicate the value of the diameter comprising respectively 25, 50 and 75% of the total number of members.

(54) Making of the Tissue Mass

(55) The fatty tissue is prepared following the protocols used for an auto-transplantation. After liposuction, the fatty tissue is centrifuged and we only recover the lipid phase that forms the supernatant, the blood elements remaining in the bottom of the centrifugation tube. The lipid phase contains adipocytes.

(56) We collect several sheets of each of the textiles referenced A to E. We cut 4 cm diameter disks in each of the textiles and we make a stacking of these disks. On one face of each disk, we dispose cells of the aforementioned supernatant with a 25 ml pipette. The supernatant is spread out in order to obtain a constant thickness of adipocytes over each disk. We obtain stackings formed by textile disks spaced by a layer of adipocytes. Afterwards, each stacking is wrapped in a Parafilm M® type film and the set is placed for 24 hours at 37° C. Afterwards, we remove the film and we examine the aspect of the tissue mass thus formed.

(57) Study of the Properties of the Tissue Mass

(58) We have made tissue masses as previously explained with the different textile samples. Afterwards, we have compared some properties of the obtained tissue masses. The following results concern the masses obtained respectively with the textile A and the textile B. The textile C allows obtaining the same results as the textile B.

(59) a) External Aspect of the Tissue Mass

(60) FIG. 4 represents the tissue masses A and B obtained according to the aforementioned protocol, respectively with disks of the textile A and disks of the textile B. In FIG. 4, we notice that the disks of the textile B do not enable holding of the mass when the film is removed. We notice that the mass B presents an expansion of its diameter by about 25% which corresponds to a peripheral collapse of the formed layered structure. On the contrary, the tissue mass A, obtained with the textile A, keeps its shape and does not expand.

(61) b) Cohesion in an Aqueous Medium (Physiologic Serum 9:100 NaCl Water)

(62) We plunge a tissue mass of a smaller size into a physiologic serum (9:100) in order to assess its cohesion. FIG. 5 shows, in the tube to the left, a tissue mass A plunged into water and in the tube to the right, a tissue mass B plunged into water. We notice that the mass A remains in one piece which floats on the surface of water whereas for the mass B, the latter has completely fallen apart and forms a suspension in water.

(63) c) Study of the Cohesion Holding Over Time

(64) FIG. 6 represents the aspect of the mass A obtained with disks of the textile A and that of the mass B obtained with disks of the textile B, after 24 h; both masses are placed in a physiologic serum. We notice in FIG. 6, that the mass A remains homogeneous despite the drainage of its surface due to the evaporation of the medium. The mass B falls apart and adipose cells of the supernatant are found in the medium.

(65) d) Dissection of the Tissue Mass

(66) FIG. 7 shows to the right a cross-section of the mass A made with the scalpel and, to the left, a cross-section of the tissue mass B. We notice that the structure of the mass A is homogeneous which allows obtaining neat slices. The mass B is hardly cut and releases fatty heaps which fall from the tissue mass.

(67) e) Peel-Off Test

(68) The principle consists in peeling off a disk from each tissue mass A and B and observing whether or not the adipose cells remain on the peeled textile disk. The results are shown in FIG. 8. For the mass A, we observe that the textile disk is completely covered with adipose cells whereas for the mass B, the textile B is easily removed and on cell remains hooked to its surface.

(69) f) Microscopic Observation

(70) FIG. 9 represents photographs obtained with an optical microscope (indicate the magnification and the type of microscope used) of a sheet of the textile A (to the top) and of a sheet of the textile B on which the aforementioned supernatant has been deposited (for more than 24 hours). We notice that the supernatant spreads out uniformly throughout the entire structure of the textile for the textile A while there are areas devoid of supernatant for the textile B (paler areas, in the bottom right of photograph B2).

(71) The aforementioned results indicate that sheets of the textile A allow obtaining a tissue mass which is homogeneous, compact and which can be cut in order to confer it with a desired shape, for example. This mass being compact, it can also be incised in particular in order to introduce a vascular pedicle therein with neither decohesion nor alteration of the mass.