Implantable device, in particular for the reconstruction of the hypodermis

Abstract

The present invention relates to a bioresorbable implantable device comprising a base structure comprising at least one base layer (10) comprising: • - an assembly A (1A) comprising a layer of a plurality of elongate elements A1 (1A1) which are oriented in a longitudinal direction LA1, and a layer of a plurality of elongate elements A2 (1A2); an assembly B (1B) comprising a layer of a plurality of elongate elements B1 (1B1) which are oriented in a longitudinal direction LB1, and a layer of a plurality of elongate elements B2 (1B2); • - the assembly B (1B) is placed at least partially on top of the assembly A (1A); • - the direction LA1 intersects the direction LB1; and • - the base structure comprises a plurality of base layers placed at least partially one on top of the other.

Description

[0001] DESCRIPTION

[0002] Title of the invention: Implantable device, in particular for reconstructing the hypodermis

[0003] Technical Field

[0004] The present invention relates to an implantable device, in particular for reconstructing the hypodermis, as well as a method for manufacturing said device.

[0005] The present invention relates to an implantable device for replacing and / or reconstructing and / or increasing a volume of soft tissue, in particular following the removal of a volume of soft tissue from a subject, in particular a volume of adipose tissue.

[0006] Without limitation, the volume of soft tissue removed from the subject may be a tumor, a portion of hypodermis, a portion of adipose tissue or a volume of breast tissue or a combination thereof.

[0007] State of the art

[0008] The skin is an envelope that covers our body. It represents 1 / 3 of the weight of the human body and has a surface area of ​​approximately 2 m 2 in an adult.

[0009] The skin is a complex organ, divided into three superficial to deep layers: the epidermis, the dermis, and the hypodermis. The entire skin is separated from the underlying organs by fascia.

[0010] The epidermis, or superficial layer, protects the body against external aggressions. It forms, following the migration of keratinocytes: a covering epithelium, stratified, squamous and keratinized.

[0011] Its thickness varies depending on the location and is determined by the thickness of the horny layer.

[0012] The epidermis is constantly renewing itself; it takes an average of 21 days to renew itself. The dermis is a support and nutrition tissue for the epidermis. The dermis is a complex connective tissue; unlike the epidermis, it is richly vascularized. Its thickness is greater than that of the epidermis (0.5 to 2 mm compared to 0.1 mm). The dermis gives elasticity and tone to the skin due to the presence of fibrous proteins. The hypodermis or subcutaneous tissue separates the dermis from the underlying muscles and bones. The hypodermis is the innermost and thickest layer of the skin. The hypodermis has mechanical, aesthetic, protective, and metabolic functions. It is formed of loose connective tissue containing fat cells. Its thickness varies greatly depending on the individual, age, body location, and nutrition.

[0013] Many injuries can affect, and therefore destroy or damage, the hypodermis depending on the area of ​​the body, more or less extensive, with serious after-effects. Every day in the world, we observe approximately 32,000 serious traumas with serious after-effects for which the hypodermis would be affected. These are burns of the 3 ieme and 4 ieme skin lesions, tumor resections, or following frostbite, ulcers or in the case of congenital defects. These traumas can be caused by explosive devices, firearms, or occur following transport accidents, or during domestic accidents.

[0014] A first way to reconstruct the hypodermis consists of transplanting an autologous flap, that is to say a total and vascularized skin graft. This surgical technique is long, difficult to implement, painful for the patient, and is only suitable for small wounds.

[0015] A second reconstruction option involves intradermal injections of non-autologous filler (e.g., hyaluronic acid). This type of surgery is minimally invasive, but the injected product is not autologous. Furthermore, the filler is not permanent. Finally, this type of reconstruction can only be performed on very small wounds.

[0016] A third way of reconstruction involves taking non-vascularized adipose tissue, processing it, and then reinjecting it by transfer (for example, lipofilling) into the area to be treated. The advantage is that this type of surgery is minimally invasive but requires multiple interventions spaced out over time to achieve the desired appearance and / or to fill the loss of injected adipose tissue.

[0017] The removal and subsequent injection of adipose tissue with a cannula having a small internal diameter (usually around 4 mm) exerts shear and abnormal pressure on the cells, which reduces initial cell viability. In addition, damaged cells are reinjected into a restricted space without direct access to nutrients and growth factors via the vascular network. As a result, there is an unpredictable loss of volume of adipocyte tissue of up to 80%.

[0018] There is currently no effective, rapid, simple and affordable surgical solution for reconstructing soft tissue, particularly the hypodermis.

[0019] The absence of reconstruction causes psychological, aesthetic and functional after-effects in the patient.

[0020] There is therefore a need for an implantable device for reconstructing soft tissue that must remain flexible, compressible, lightweight, and cuttable to a specific shape while maintaining its structure, cohesion, and mechanical properties.

[0021] There is also a need for a bioresorbable implantable device configured to receive a given volume of initial adipose tissue before implantation and capable of retaining this volume of adipose tissue as much as possible without significant loss of volume or requiring the addition of a new volume of fat into the implantable device after implantation.

[0022] There is a need for an implantable device that improves the behavior of the implanted adipose tissue volume in terms of: cell migration and proliferation, fat cell insertion and retention, and cell viability.

[0023] Finally, there is a need for an implantable device for reconstruction and / or replacement and / or augmentation of soft tissue that facilitates the surgical procedure, in particular by avoiding having to rework the cut edges of the implantable device after its shaping and filling it with a new volume of adipose tissue.

[0024] Statement of the invention

[0025] The subject of the present invention, according to a first aspect, is an implantable device, in particular bioresorbable, in particular for the replacement and / or reconstruction and / or augmentation of soft tissue, for example for the reconstruction and / or replacement of the hypodermis or for the replacement and / or reconstruction and / or breast augmentation, comprising a base structure, said base structure comprising at least one base layer, and said base layer comprising:

[0026] - an assembly A comprising a layer of several elongate elements Al, spaced from each other, and oriented in a longitudinal direction LAI, and a layer of several elongate elements A2, spaced from each other, and oriented in a longitudinal direction LA2, the directions LAI and LA2 being intersecting;

[0027] - a set B comprising a layer of several elongate elements Bl, spaced from each other, and oriented in a longitudinal direction LB1 and a layer of several elongate elements B2, spaced from each other, and oriented in a longitudinal direction LB2, the directions LB1 and LB2 being intersecting;

[0028] - set B is superimposed at least in part, in particular is superimposed, on set A;

[0029] - the LAI direction is intersecting with the LB1 direction;

[0030] - and the implantable device comprises a base structure comprising several base layers at least partially superimposed.

[0031] The inventors have discovered that the implantable device according to the invention offers numerous advantages, in particular concerning the volume of adipose tissue removed by liposuction and introduced into the implantable device: improves cell migration and proliferation, facilitates insertion into the entire thickness of the basic structure and the retention of fat cells in said structure, improves initial cell viability, and reduces long-term cell death. The superposition of elongated elements selected within the scope of the present invention makes it possible to create open and connected pores of various sizes allowing the reception and maintenance of different types of fat (for example macrofat, milifat, microfat or even nanofat, the name of which depends on the size of the fat removal cannula).

[0032] The implantable device also advantageously facilitates the surgical procedure because it is not necessary to re-inject a new volume of adipose tissue after implantation in the implantable device to compensate for the initial loss of adipose tissue.

[0033] In addition, the harvested adipose tissue can be applied by spreading to penetrate the thickness of the implantable device, which avoids shearing the cells when they are introduced into the implantable device and thus improves their initial cell viability.

[0034] The implantable device is also advantageously divisible without loss of its cohesion, and can therefore be adapted by cutting to the dimensions of the anatomical area to be treated, in particular to be filled and / or reconstructed. The implantable device according to the invention is advantageously customizable while being able to be manufactured industrially.

[0035] The observed advantages were evaluated compared to a reconstruction technique using only a layer of adipose tissue placed in the defect to be treated.

[0036] The implantable device according to the invention is generally used for filling any anatomical defect comprising adipose tissue, in particular non-vascularized or vascularized, preferably non-vascularized.

[0037] The implantable device is preferably suitable for hypodermal reconstruction or breast reconstruction.

[0038] Advantageously, the implantable device is configured to allow the reconstruction and / or replacement of the hypodermis but is also compatible with techniques for reconstructing the dermis and the epidermis.

[0039] In this text, the basic structure comprises n+1 basic layers, with n being an integer greater than or equal to 1.

[0040] In this text, an n+1 base layer is similar in construction to an n base layer.

[0041] Preferably, a base layer n+1 is superimposed on a base layer n such that at least one elongate element Al (or respectively A2) of the set A of the base layer n+1 is substantially parallel to at least one elongate element Al (or respectively A2) of the set A of the base layer n. Preferably, a base layer n+1 is superimposed on a base layer n without rotation of the set A of the layer n+1 relative to the set A of the layer n.

[0042] Preferably, a base layer n+1 is superimposed on a base layer n so that at least one elongate element Al (in particular B1 or Cl), and at least one elongate element A2 (in particular B2 or C2), of a set A (in particular of a set B or C) of the layer n+1 are substantially parallel respectively to at least one elongate element Al (in particular B1 or Cl), and at least one elongate element A2 (in particular B2 or C2), of a set A (in particular of the set B or C) of the layer n.

[0043] Preferably, a base layer n+1 is superimposed on a base layer n so that the direction LAI (in particular LB1 or LC1) and the direction LA2 (in particular LB2 or LC2) of the layer n+1 are substantially parallel respectively to the direction LAI (in particular LB1 or LC1) and to the direction LA2 (in particular LB2 or LC2), of a set A (in particular of a set B or C), of the layer n.

[0044] Implantable device

[0045] Advantageously, the basic structure comprises open and connected pores.

[0046] The grease taken and applied to one side of the basic structure thus diffuses through the basic structure, and remains maintained in the basic structure thanks to the network of open pores, connected to each other and having varied sizes.

[0047] In particular, the basic structure comprises open pores having a size greater than 1 mm, open pores having a size greater than or equal to 1 pm and less than or equal to 1 mm, and open pores having a size less than or equal to 1 pm and greater than or equal to 1 nm.

[0048] In this text, open and connected pores are understood to mean that said pores are in fluid communication with each other.

[0049] Advantageously, the basic structure, in particular the implantable device, is a plate having a determined thickness, in particular the general shape of which depends on the final application.

[0050] Advantageously, the basic structure, in particular the implantable device, may be manufactured in the form of a rectangular or square plate or in any determined three-dimensional shape, for example in the form of a dome, from which the structure may be resized, in particular by cutting, to conform to the defect of the subject to be treated.

[0051] In one embodiment, the basic structure is manufactured, in particular in three dimensions, according to a tailor-made shape corresponding specifically to the patient's defect (the determined shape of the basic structure is called patient-specific). Preferably, the basic structure is manufactured by three-dimensional printing.

[0052] The basic structure, in particular the implantable device, can thus have any shape: rectangular, square, disc, or even dome.

[0053] Preferably, the base structure, in particular the implantable device, comprises a first face and a second face substantially opposite said first face. The first face is advantageously in fluid communication with the second face via open and connected pores.

[0054] Preferably, the basic structure, in particular the implantable device, comprises open, connected pores opening onto its first face and onto its second face.

[0055] In one embodiment, the basic structure, in particular the implantable device, has a substantially homogeneous determined thickness, in particular corresponding to the distance separating the first face from the second face of the basic structure.

[0056] For example, the basic structure, in particular the implantable device, has a substantially constant thickness of between 0.5 mm and 50 mm, preferably a thickness of between 1 mm and 20 mm, in particular for the reconstruction and / or replacement of the hypodermis.

[0057] For example, the basic structure (in particular for the reconstruction and / or replacement of the hypodermis), in particular the implantable device, has a thickness greater than or equal to 2 mm or 3 mm or 4 mm or 4.5 mm, and preferably less than or equal to 15 mm or 10 mm or 8 mm or 6 mm or 5 mm.

[0058] In one embodiment, the base structure, in particular the implantable device, has a variable thickness, in particular corresponding to the distance separating the first face from the second face of the implantable device. For example, the base structure, in particular the implantable device, has a general dome shape.

[0059] For example, the basic structure, in particular the implantable device, has a variable thickness between 0.5 mm and 150 mm, preferably between 0.5 mm and 65 mm, in particular for breast reconstruction and / or replacement and / or augmentation.

[0060] In particular, when the basic structure is a dome, the value of 65 mm corresponds to the top of the dome.

[0061] In the present text, it is understood by a value between a and b that the lower bounds a and upper bounds b are included in said interval. In one example, the implantable device comprises, in particular is essentially made up of, several base layers superimposed on each other, and possibly a set A and / or a set B and / or a set C, and possibly one or more functional agent(s).

[0062] In one embodiment, in particular for the reconstruction and / or replacement of the hypodermis, the base structure comprises from 2 to 20 base layers, in particular from 3 to 20 base layers, preferably from 2 to 10 base layers, more preferably from 2 to 6 base layers, in particular from 3 to 5 base layers, in particular 3 base layers (in particular each comprising sets A, B and C) and a partial base layer consisting essentially of sets A and / or B.

[0063] In one embodiment, the base structure comprises 4 base layers, in particular each comprising sets A, B and C, and optionally at least one set A and / or B and / or C.

[0064] In one embodiment, a base layer (particularly comprising sets A, B and C) has a thickness of between 0.8 mm and 1.5 mm, preferably of the order of 1.1 mm to + / - 0.1 mm.

[0065] In one embodiment, a base layer has a thickness of between 0.5 mm and 1.5 mm.

[0066] In one example, the basic structure comprises, in particular is essentially made up of, several basic layers superimposed on each other, and possibly an additional set A and / or set B and / or set C.

[0067] The base layers are superimposed on each other until the desired final thickness for the base structure, particularly for the implantable device, is obtained. It is possible for the last base layer to be only partial, i.e. it only includes one set A, or one set A and one set B, in order to achieve the desired final thickness precisely.

[0068] Advantageously, the volume of adipose tissue placed in the porous volume of the basic structure, in particular the implantable device, is autologous.

[0069] Advantageously, the volume of adipose tissue placed in the porous volume of the basic structure, in particular the implantable device, is not vascularized.

[0070] Advantageously, the implantable device, in particular bioresorbable, and / or the base structure, and / or at least one of the base layers and / or the base layers, comprises / comprise, in particular is / are essentially constituted of one or more (co)polymer(s), in particular bioresorbable, as described in the present text. Functional agent(s)

[0071] Advantageously, the basic structure may be treated, for example impregnated or coated with one or more functional agent(s).

[0072] Preferably, a functional agent is any active substance, aimed at:

[0073] - (i) to improve cellular and tissue regeneration (for example promoting adipocyte growth, proliferation and / or differentiation) and / or the maintenance of the extracellular matrix; and / or

[0074] - (ii) to limit or inhibit the growth of microorganisms; and / or

[0075] - (iii) to inhibit a localized inflammatory reaction and to prevent the development of fibrosis.

[0076] Preferably, one or more functional agent(s):

[0077] - is / are chosen from a list I comprising (in particular consisting essentially of) growth factors promoting angiogenesis (proangiogenic), such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1 (SDF-1), any cellular fraction such as platelet-rich plasma (PRP) or platelet lysates;factors promoting cell proliferation, cell migration and adipocyte differentiation such as fibroblast growth factor (FGF), insulin-like growth factor (IGF), corticosteroids such as dexamethasone, hormones such as insulin, therapeutic agents such as 3-isobutyl-l methylxanthine (IBMX); stromal vascular fraction (SVF); factors promoting cell adhesion such as fibronectin, polydopamine; and / or;

[0078] - is / are chosen from a list II comprising (in particular consisting essentially of): cells chosen from adipocytes, cells capable of differentiating into adipocytes, mixtures of cells chosen from adipocytes and cells capable of differentiating into adipocytes, preferably said cells originate from the patient being treated, or a mixture of the latter; and / or

[0079] - is / are chosen from a list III comprising (in particular consisting essentially of): anti-thrombotics, in particular anti-coagulants, such as heparin, anti-platelet agents such as aspirin, thrombolytics for destroying a blood clot in place; anti-parasitic molecules; anti-inflammatories; vitamins; antiseptics (for example betadine); antibiotics; or a mixture of these;and / or - form(s) a bioresorbable polymeric matrix, in particular the bioresorbable polymeric matrix is ​​a hydrogel, preferably the functional agent(s) is / are then chosen from a list IV comprising (in particular consisting essentially of): cyclodextrins, cyclodextrin derivatives, gelatin, chitosans, lactic acid (co)polymer(s) (L or D form), glycolic acid (co)polymer(s), copolymers of lactic acid and glycolic acid, copolymers of lactic acid (L or D form) or glycolic acid and caprolactone, caprolactones, poly-p-dioxanone polymer, carrageenans, collagen or other molecules mimicking the structure and organization of the extracellular matrix, or a mixture thereof.;

[0080] In one embodiment, the base structure is coated at least in part with functional agent(s) forming a bioresorbable polymeric matrix, in particular chosen from list IV, optionally in admixture with one or more functional agent(s) chosen from list I and / or from list II and / or from list III.

[0081] Preferably, the functional agent(s) selected from list II is / are one or more volumes of adipose tissue arranged at least partly in the porous volume of the basic structure. Preferably, the volume(s) of adipose tissue is / are autologous.

[0082] In a first example, the implantable device comprises a coating, in particular in a bioresorbable polymer matrix as described in the present text, optionally said coating comprising one or more functional agent(s) chosen from list I and / or list II and / or from list III, coating entirely or in part at least one face of the basic structure, in particular coating entirely or in part the first face and / or the second face of the basic structure.

[0083] In a second example, optionally combined with the first example, at least a portion of the walls of the open and connected pores is coated with a coating, in particular in a bioresorbable polymeric matrix as described in the present text, optionally said coating comprising one or more functional agent(s) chosen from list I and / or list II and / or from list III, in particular said coating comprises at least one volume of adipose tissue.

[0084] Preferably, an elongate element is a portion of a monofilament yarn or a cord, in particular extruded from a mixture comprising at least one (co)polymer. Thus, advantageously at least a portion of the elongate elements chosen from the elongate elements A1 (in particular 1A1, 2A1), A2 (in particular 2A1, 1A2), B1 (in particular 1B1, 2B1), and B2 (in particular 1B2, 2B2), in particular C1 (in particular 1C1, 2C1) and C2 (in particular 1C2, 2C2), are portions of monofilament yarn(s) or cords, in particular extruded from a mixture comprising at least one (co)polymer, in particular the (co)polymer described in the present text.

[0085] Preferably, the basic structure is obtained by additive manufacturing, more particularly by three-dimensional printing of elongated elements Al, B1 and Cl, and in particular A2, B2 and C2.

[0086] Preferably, the basic structure comprises elongated elements A1 and / or A2 and / or B1 and / or B2 and / or C1 and / or C2 each comprising a portion having a diameter or a width of between 0.01 mm and 0.80 mm, more preferably between 0.01 mm and 0.50 mm, preferably between 0.01 mm and 0.30 mm, in particular between 0.10 mm and 0.30 mm.

[0087] Preferably, said elongated element, in particular said portion of monofilament thread or said cord, comprises, in particular consists essentially of, at least one bioresorbable (co)polymer.

[0088] In one embodiment, at least a portion of the elongate elements chosen from the elongate elements A1 (in particular 1A1, 2A1), A2 (in particular 2A1, 1A2), B1 (in particular 1B1, 2B1), and B2 (in particular 1B2, 2B2), in particular C1 (in particular 1C1, 2C1) and C2 (in particular 1C2, 2C2), comprises, in particular consists essentially of, at least one bioresorbable (co)polymer.

[0089] The (co)polymer may be a homopolymer or a copolymer or a terpolymer. Said (co)polymer may be chosen from: lactic acid (co)polymer(s), such as PLLA or PDLA, and PLA; E-caprolactone (co)polymer(s); polydioxanones; glycolic acid (co)polymer(s), such as PLGA; glycolic acid and lactic acid (co)polymer(s); lactic acid and E-caprolactone (co)polymer(s).

[0090] Preferably, said (co)polymer comprises at least two different repeating units.

[0091] Preferably, said (co)polymer is a polymer of E-caprolactone and at least one repeating unit different from E-caprolactone, for example derived from lactic acid and / or derived from glycolic acid.

[0092] Preferably, the repeating units derived from lactic acid may be L-form lactic acid repeating units and / or D-form lactic acid repeating units and / or D, L-form lactic acid repeating units. Preferably, said at least one (co)polymer comprises E-caprolactone repeating units whose molar fraction (in said (co)polymer) is less than or equal to 50%, more preferably less than or equal to 40%, in particular between 20% and 40% (limits included).

[0093] Preferably, said at least one (co)polymer comprises repeating units of lactic acid of L form and / or repeating units of lactic acid of D form and / or of D,L form whose molar fraction (in said (co)polymer) is greater than or equal to 50%, more preferably greater than or equal to 60%, in particular between 60% and 80% (limits included).

[0094] Said molar fractions can be determined by NMR spectroscopy.

[0095] Preferably, said at least one (co)polymer comprises repeating units of L-form lactic acid, and / or repeating units of D-form lactic acid and / or D-form, L-form lactic acid, the molar fraction of which is less than or equal to 90%, more preferably less than or equal to 80%.

[0096] In this text, an element consists essentially of one or more sub-element(s) as meaning that the said sub-element(s) represent(s) at least 80% by mass or volume, in particular at least 90% by mass or volume, of the said sub-element(s).

[0097] Advantageously, the layers of elongated elements Al and A2 are superimposed.

[0098] Advantageously, the layer of elongate elements A2 is placed above the layer of elongate elements Al.

[0099] Advantageously, the elongated elements Al are arranged substantially parallel to each other, and spaced apart from each other.

[0100] Advantageously, the elongated elements A2 are arranged substantially parallel to each other, and spaced apart from each other.

[0101] Advantageously, the layers of elongated elements B1 and B2 are superimposed.

[0102] Advantageously, the layer of elongate elements B2 is placed above the layer of elongate elements Bl.

[0103] Advantageously, the elongated elements Bl are arranged substantially parallel to each other, and spaced apart from each other.

[0104] Advantageously, the elongated elements B2 are arranged substantially parallel to each other, and spaced apart from each other.

[0105] Advantageously, set B is superimposed on set A according to an angle of rotation corresponding to the angle formed at the intersection of directions LAI and LB1.

[0106] The angle of rotation is measured clockwise, and therefore inversely to the trigonometric direction.

[0107] This arrangement makes it possible to generate open and connected pores of various sizes and shapes. In an alternative embodiment, the base layer comprises an assembly C comprising a layer of several elongate elements C1, spaced from each other, and oriented in a longitudinal direction LC1 and a layer of several elongate elements C2, spaced from each other, and oriented in a longitudinal direction LC2, the directions LC1 and LC2 being intersecting, the assembly C is superimposed at least in part on the assembly B, in particular the direction LC1 is intersecting with the direction LB1.

[0108] It has also been advantageously observed that blood vessels can be established from set A to set C in a base layer via the interconnected pores. Thus, vascularization of the base structure throughout its thickness is observed.

[0109] Advantageously, the superposition of three sets A, B and C makes it possible to create a network of open and connected pores having even more varied sizes and facilitating the reconstruction of the soft tissue.

[0110] Advantageously, the layers of elongated elements C1 and C2 are superimposed.

[0111] Advantageously, the layer of elongate elements C2 is placed above the layer of elongate elements Cl.

[0112] Advantageously, the elongated elements Cl are arranged substantially parallel to one another, and spaced apart from one another.

[0113] Advantageously, the elongated elements C2 are arranged substantially parallel to each other, and spaced apart from each other.

[0114] Advantageously, set C is superimposed on set B according to an angle of rotation corresponding to the angle formed at the intersection of directions LB1 and LC1.

[0115] In an alternative embodiment, the direction LAI intersects with the direction LB1 and forms at their intersection an angle λ greater than or equal to 10° and less than or equal to 60°, in particular greater than or equal to 20° and less than or equal to 45°, in particular greater than or equal to 30° and less than or equal to 40°, for example of the order of 36°.

[0116] In an alternative embodiment, the set B is superimposed on the set A while being pivoted by said angle λ1.

[0117] Advantageously, the elongate elements B1 are pivoted by said angle λ1 relative to the elongate elements A1.

[0118] In an alternative embodiment, the direction LAI intersects with the direction LC1 and forms at their intersection an angle λ3 greater than λ by at least 10°, in particular approximately twice λ. Preferably, λ3 is greater than or equal to 40° and less than or equal to 90°, more preferably greater than or equal to 60° and less than or equal to 80°. Advantageously, the assembly C is superimposed on the assembly B while being pivoted by an angle λ2 of at least 10°. Preferably, the angle λ2 is greater than or equal to 10° and less than or equal to 60°, in particular greater than or equal to 20° and less than or equal to 45°, in particular greater than or equal to 30° and less than or equal to 40°, for example of the order of 36°. Preferably, the angle λ2 is substantially equal to λ.

[0119] Advantageously, the sets A, B and C are not superimposed in a base layer so that the elongated elements Al, B1 and Cl are aligned in parallel directions.

[0120] The superposition of sets A, B and C in this way makes it possible to secure the layers of elongated elements (Al, A2, Bl, B2, Cl, C2) together and also makes it possible to increase the contact surface between these layers. If such a rotation were not carried out, we would obtain conduits with a perfectly reproducible shape.

[0121] It has also been observed that this arrangement advantageously contributes to the placement and orientation of blood vessels in set A and up to set C in a base layer via the interconnected pores. We thus advantageously observe a vascularization of the base structure throughout its thickness.

[0122] In an alternative embodiment, the angle formed between the direction LAI and the direction LA2 is greater than or equal to 70° and less than or equal to 110°, in particular between 80° and 100°, more particularly between 85° and 95°, in particular approximately 90°.

[0123] In an alternative embodiment, the angle formed between the direction LB1 and the direction LB2 is greater than or equal to 70° and less than or equal to 110°, in particular between 80° and 100°, more particularly between 85° and 95°, in particular approximately 90°.

[0124] In an alternative embodiment, the angle formed between the direction LC1 and the direction LC2 is greater than or equal to 70° and less than or equal to 110°, in particular between 80° and 100°, more particularly between 85° and 95°, in particular approximately 90°.

[0125] In an alternative embodiment, the distance separating two adjacent elongate elements Al, respectively A2, in a layer of several elongate elements Al, respectively A2, of a set A is between 2 mm and 8 mm, preferably between 3 mm and 6 mm, more preferably between 3.5 mm and 4.5 mm, in particular of the order of 4 mm.

[0126] This arrangement allows to play on the size of the open pores, and to offer a compromise in order to retain small cellular aggregates (for example microfat) and larger cellular aggregates (for example macrofat).

[0127] It has also been observed that this distance promotes good penetration, dispersion and retention of fatty tissue throughout the thickness of the base structure. In an alternative embodiment, the distance separating two adjacent elongate elements B1, respectively B2, in a layer of several elongate elements B1, respectively B2, of a set B is between 2 mm and 8 mm, preferably between 3 mm and 6 mm, more preferably between 3.5 mm and 4.5 mm, in particular of the order of 4 mm.

[0128] In an alternative embodiment, the distance separating two adjacent elongate elements C1, respectively C2, in a layer of several elongate elements C1, respectively C2, of a set C is between 2 mm and 8 mm, preferably between 3 mm and 6 mm, more preferably between 3.5 mm and 4.5 mm, in particular of the order of 4 mm.

[0129] In an alternative embodiment, at least one elongate element Al is secured to several elongate elements A2 by means of solidified thermofused portions originating from said elongate element Al and / or the elongate elements A2. The elongate elements A2 are superimposed, in a partially softened state, on the elongate elements Al, also in a partially softened state, so that they adhere to each other at their intersections, which creates anchoring points between the layer of elements Al and the layer of elements A2.

[0130] This arrangement promotes the cohesion and tear resistance of the basic structure, and thus allows it to be cut to the desired dimensions without loss of its structure.

[0131] In an alternative embodiment, at least one elongate element B1 is secured to several elongate elements B2 by means of solidified thermofused portions originating from said elongate element B1 and / or the elongate elements B2.

[0132] In an alternative embodiment, at least one elongate element C1 is secured to several elongate elements C2 by means of solidified thermofused portions originating from said elongate element C1 and / or the elongate elements C2.

[0133] In an alternative embodiment, at least one elongate element Al comprises at least one portion ail of its length in a zigzag or sinusoidal form.

[0134] Advantageously, said garlic portion comprises hollows and peaks.

[0135] This arrangement makes it possible to improve the flexibility, and therefore the ability to deform, of the assembly A, and therefore of the base layer, and ultimately of the base structure.

[0136] Advantageously, at least one elongate element A2 comprises at least one portion a22 of its length in a zigzag or sinusoidal shape, in particular comprising troughs and peaks.

[0137] Advantageously, at least one elongate element B1 comprises at least one portion b11 of its zigzag or sinusoidal length, in particular comprising troughs and peaks. Advantageously, at least one elongate element B2 comprises at least one portion b22 of its zigzag or sinusoidal length, in particular comprising troughs and peaks.

[0138] Advantageously, at least one elongate element Cl comprises at least one portion C1 of its length in a zigzag or sinusoidal shape, in particular comprising troughs and peaks.

[0139] Advantageously, at least one elongate element C2 comprises at least one portion C22 of its zigzag or sinusoidal length, in particular comprising troughs and peaks.

[0140] In an alternative embodiment, at least one elongate element A2 comprises at least one portion a22 of its length in a zigzag or sinusoidal shape, said portion a22 comprising hollows spaced from each other, and the portion a11 of said elongate element A1 is superimposed with the portion a22 of said elongate element A2 passing through a hollow of said portion a22 in a zigzag or sinusoidal shape.

[0141] This arrangement allows the stacking of layers of elongated elements to be blocked between them, and provides stability to the basic structure.

[0142] In the preceding variants, preferably a zigzag or sinusoidal portion is repeated over the entire length of an elongated element, in particular A1 and / or A2 and / or B1 and / or B2 and / or C1 and / or C2.

[0143] In a variant, at least one elongate element Al, respectively B1 or Cl, comprises at least one sinusoidal or zigzag portion comprising troughs and peaks, and at least one elongate element A2, respectively B2 or C2, comprises at least one sinusoidal or zigzag portion comprising troughs and peaks, said at least one elongate element Al, respectively B1 or Cl, is superimposed with said at least one elongate element A2, respectively B2 or C2, so that the troughs, respectively the peaks, of said at least one elongate element Al cooperate with the peaks, respectively the troughs, of said at least one elongate element A2.

[0144] In an alternative embodiment, the basic structure has a density greater than or equal to 0.01 g / cm 3 and less than or equal to 1 g / cm 3 , preferably less than or equal to 0.1 g / cm 3 , still preferably less than or equal to 0.05 g / cm 3 .

[0145] In one variant, at least a portion of the elongate elements chosen from the elongate elements A1, A2, B1, and B2, in particular C1 and C2, are portions of monofilament yarns each having a diameter or width less than or equal to 0.60 mm, preferably less than or equal to 0.40 mm, in particular between 0.10 mm and 0.30 mm, in particular of the order of 0.20 mm. In one embodiment, the basic structure comprises open and connected micropores, open and connected millipores and open and connected macropores.

[0146] In this text, micropores are understood to mean pores having at least one dimension less than or equal to 1.2 mm, in particular between 0.1 mm and 1.2 mm.

[0147] The size of the micropores of the basic structure is advantageously adapted to receive the cellular aggregates corresponding to the so-called microfat category and taken with a cannula whose internal diameter is less than or equal to 1.2 mm and preferably greater than or equal to 0.1 mm.

[0148] In this text, millipores are understood to mean pores having at least one dimension less than or equal to 2.4 mm, in particular between 1.2 mm and 2.4 mm.

[0149] The size of the millipores of the basic structure is advantageously adapted to receive the cellular aggregates corresponding to the so-called millifat category (millifat) and taken with a cannula whose internal diameter is less than or equal to 2.4 mm and preferably greater than or equal to 1.2 mm.

[0150] In this text, macropores are understood to mean pores having at least one dimension greater than 2.4 mm, in particular between 2.4 mm and 10 mm.

[0151] The size of the macropores of the basic structure is advantageously adapted to receive the cellular aggregates corresponding to the so-called macrofat category and taken with a cannula whose internal diameter is greater than 2.4 mm, preferably greater than or equal to 4 mm, still preferably less than or equal to 10 mm.

[0152] It has thus been observed that the basic structure advantageously comprises micropores, millipores and macropores whose sizes are adapted to receive different sizes of cell aggregates in relation to the different internal diameters of the cannulas for collecting said adipose cells. In an alternative embodiment, at least 50% in number of the open pores of the basic structure have at least one dimension less than or equal to 1.25 mm.

[0153] In an alternative embodiment, at least 10% by number of the open pores of the basic structure have at least one dimension greater than or equal to 1.25 mm.

[0154] In an alternative embodiment, at least 10% by number of the open pores of the basic structure have at least one dimension greater than or equal to 1.25 mm and less than or equal to 2.5 mm.

[0155] In an alternative embodiment, at least 5% by number of the open pores of the basic structure have at least one dimension greater than or equal to 2.5 mm. In an alternative embodiment, the basic structure comprises from 50% to 65% by number of pores having a diameter less than or equal to 1.25 mm, in particular greater than or equal to 0.5 mm, from 25% to 45% by number of pores having a diameter between 1.25 mm and 4 mm, and from 5% to 10% by number of pores having a diameter greater than or equal to 4 mm.

[0156] In one variant, at least 40% by number, preferably at least 60% by number, more preferably at least 80% by number, of the pores of the basic structure have a size greater than or equal to 0.5 mm. Preferably, the method for determining the pore size and their number distribution (%), preferably comprises the following steps:

[0157] - Binocular image capture using an XL0 lens with an apparent ruler, particularly seen from above;

[0158] - Measurement for each test of the size of approximately 100 pores on a sample, repeating the measurement at least 3 times;

[0159] - Import into ImageJ 1.53t software;

[0160] - Defining the image in 8-bit using the “Image > Type > 8-bit” tool;

[0161] - Definition of the scale by the “Analysis > Set Scale” tool using the visible ruler;

[0162] - Binarization of the image with the “Image > Adjust > Threshold” tool;

[0163] - Highlighting pores by variation of limits;

[0164] - “Analyze > Analyze particles” with Size(pixel A 2): 2-Infinity, Circularity [0.00- 1.00] and the “exclude on edges” box checked;

[0165] - Saving the generated table in csv;

[0166] - Import the table into Excel by separating the information to obtain a column “” (count), “Area”, “Mean”;

[0167] - Class distribution;

[0168] - Determination of the percentage of each class.

[0169] Preferably, the size of the pores is measured by optical microscopy of sections (therefore in two dimensions) of the basic structure or of the implantable device, in particular an average is taken over approximately 100 measurements taken along each of the three axes X, Y, and Z (in particular 3D printing of the basic structure).

[0170] The pore size can be measured on the raw base structure or on a base structure comprising one or more functional agent(s).

[0171] In a variant, at least a portion of the elongate elements chosen from the elongate elements A1, A2, B1, and B2, in particular C1 and C2, comprises, in particular is essentially constituted by, at least one bioresorbable (co)polymer, preferably comprising repeating units of E-caprolactone and repeating units of lactide of L or D or L, D form. Said copolymer can be written in the form poly (L-lactide or D-lactide or L, D-lactide-co-E-caprolactone), in particular poly (L-lactide-co-E-caprolactone).

[0172] In one variant, said bioresorbable (co)polymer has a number-average molar mass Mn greater than or equal to 10,000 g / mol, preferably greater than or equal to 25,000 g / mol, more preferably greater than or equal to 45,000 g / mol, in particular greater than or equal to 65,000 g / mol.

[0173] In one variant, said bioresorbable (co)polymer has a number-average molar mass Mn of less than or equal to 200,000 g / mol, preferably less than or equal to 175,000 g / mol, more preferably less than or equal to 150,000 g / mol, in particular less than or equal to 120,000 g / mol or 100,000 g / mol.

[0174] In one variant, said bioresorbable (co)polymer has a mass-average molar mass Mw greater than or equal to 50,000 g / mol, preferably greater than or equal to 75,000 g / mol, more preferably greater than or equal to 100,000 g / mol, in particular greater than or equal to 125,000 g / mol.

[0175] In one variant, said bioresorbable (co)polymer has a number-average molar mass Mw of less than or equal to 300,000 g / mol, preferably less than or equal to 275,000 g / mol, more preferably less than or equal to 250,000 g / mol, in particular less than or equal to 225,000 g / mol or 200,000 g / mol.

[0176] In one variant, the polydispersity index of said at least one bioresorbable (co)polymer is less than or equal to 2.5 or 2.3 or 2.1.

[0177] In a variant, the polydispersity index (1= Mw / Mn) of the bioresorbable (co)polymer is greater than or equal to 1 or 1.3 or 1.5.

[0178] In an alternative embodiment, at least a portion, or essentially all, of the elongate elements chosen from the elongate elements A1, A2, B1, and B2, in particular C1 and C2, comprises at least one bioresorbable (co)polymer, said at least one (co)polymer comprises:

[0179] - repeating units of E-caprolactone whose molar fraction (in said (co)polymer) is less than or equal to 50%, more preferably less than or equal to 40%, in particular between 20% and 40%, and / or

[0180] - repeating units of lactic acid of L form and / or repeating units of lactic acid of D form and / or of D,L form whose molar fraction (in said (co)polymer) is greater than or equal to 50%, more preferably greater than or equal to 60%, in particular between 60% and 80%.

[0181] In an alternative embodiment, at least a portion, or essentially all, of the elongate elements chosen from the elongate elements A1, A2, B1, and B2, in particular C1 and C2, comprises, in particular is essentially constituted of, at least one bioresorbable (co)polymer having an elongation at break (%) greater than or equal to 50%, preferably greater than or equal to 100%, more preferably greater than or equal to 150%, preferentially greater than or equal to 200%, in particular measured according to the printing direction, X or Y, in three dimensions of the specimen tested.

[0182] In one embodiment, the bioresorbable (co)polymer has an elongation at break (%) less than or equal to 2000%, preferably less than or equal to 1500%, more preferably less than or equal to 1200%, in particular measured according to the printing direction, X or Y, in three dimensions of the specimen tested.

[0183] In one embodiment, the bioresorbable (co)polymer has a Young's modulus greater than or equal to 50 MPa, preferably greater than or equal to 75 MPa, in particular greater than or equal to 100 MPa (preferably regardless of the three-dimensional printing direction of the specimen tested: X, Y, Z).

[0184] In one embodiment, the bioresorbable (co)polymer has a Young's modulus less than or equal to 800 MPa, in particular less than or equal to 600 MPa (preferably regardless of the three-dimensional printing direction of the specimen tested: X, Y, Z).

[0185] Young's modulus and elongation at break are measured according to ASTM D638-14 (“Standard Test Method for Tensile Properties of Plastics”) at a tensile speed of 10 mm / min on type V specimens, preferably at a temperature of 20°C. The specimens tested are preferably manufactured by an additive manufacturing process, in particular the printing direction can vary along the X, Y or Z axes.

[0186] In one variant, the base structure has a porosity greater than or equal to 90%.

[0187] Preferably, the porosity is determined by the following calculation formula: (total volume of the basic structure - void volume of the basic structure) / total volume of the basic structure * 100.

[0188] Preferably, the total volume and the full volume of the basic structure are estimated using the SOLIDWORKS 2019-SPO4 design software (the procedure used is: 1 / “evaluate” tab, 2 / Surface selection, 3 / “measurement” option, 4 / surface value).

[0189] In an alternative embodiment, the implantable device, in particular the basic structure, has a Young's modulus greater than or equal to 5KPa, preferably less than or equal to 80 KPa, more preferably between 5 KPa and 60 KPa, in particular between 5 KPa and 50 KPa, for example between 5 KPa and 25 KPa or even of the order of 10 KPa to + / - 5 KPa.

[0190] The Young's modulus is advantageously measured according to the ASTM D1621-16 standard “Standard Test Method for Compressive Properties of Rigid Cellular Plastics”, in particular under the conditions described with reference to Figure 13. The subject of the present invention is, according to a second aspect, a method for manufacturing an implantable device, in particular according to any one of the variant embodiments with reference to the first aspect of the invention, said method comprises the steps:

[0191] - a step of manufacturing a base layer (i), said step comprising:

[0192] - a step (il) of manufacturing an assembly A comprising the deposition of several elongate elements Al, in particular extruded, spaced from each other, and oriented in a longitudinal direction LAI, so as to form a layer, then the deposition of several elongate elements A2, in particular extruded, spaced from each other, and oriented in a longitudinal direction LA2, so as to form a layer arranged above the previous layer comprising the elongate elements Al, the directions LAI and LA2 being intersecting; and

[0193] - a step (i2) of manufacturing an assembly B comprising the deposition of several elongate elements B1, in particular extruded, spaced from each other, and oriented in a longitudinal direction LB1, so as to form a layer, then the deposition of several elongate elements B2, in particular extruded, spaced from each other, and oriented in a longitudinal direction LB2, so as to form a layer arranged above the previous layer comprising the elongate elements B1, the directions LB1 and LB2 being intersecting;

[0194] - set B is superimposed at least in part on set A;

[0195] - the LAI direction is intersecting with the LB1 direction;

[0196] - and the implantable device comprises a base structure comprising several base layers at least partially superimposed.

[0197] In one embodiment, said method comprises a step (i3) of manufacturing an assembly C comprising the deposition of several elongate elements C1, spaced from each other, and oriented in a longitudinal direction LC1, so as to form a layer, then the deposition of several elongate elements C2, spaced from each other, and oriented in a longitudinal direction LC2, so as to form a layer arranged above the previous layer comprising the elongate elements C1, the directions LC1 and LC2 being intersecting;

[0198] - set C is superimposed at least in part on set B;

[0199] - the LC1 direction is intersecting with the LB1 direction.

[0200] In one example, the implantable device comprises, in particular consists essentially of, several base layers superimposed on each other, and possibly a set A and / or a set B and / or a set C, and possibly one or more functional agent(s).

[0201] Advantageously, the method comprises several steps (i) carried out one after the other, optionally followed by the performance of a step (ii) or the performance of a step (ii) followed by a step (i2), until the desired thickness is obtained for the basic structure.

[0202] In one variant, the implantable device comprises a number of base layers n+1 with n being an integer greater than or equal to 1.

[0203] In a variant, a base layer n+1 is superimposed on a base layer n so that at least one elongate element Al (or respectively A2) of the set A of the base layer n+1 is substantially parallel to at least one elongate element Al (or respectively A2) of the set A of the base layer n.

[0204] Preferably, a base layer n+1 is superimposed on a base layer n without rotation of the set A (or respectively B or C) of the layer n+1 with respect to the set A (or respectively B or C) of the layer n.

[0205] Preferably, a base layer n+1 is superimposed on a base layer n so that at least one elongate element Al (in particular B1 or Cl), and at least one elongate element A2 (in particular B2 or C2), of a set A (in particular of a set B or C) of the layer n+1 are substantially parallel respectively to at least one elongate element Al (in particular B1 or Cl), and at least one elongate element A2 (in particular B2 or C2), of a set A (in particular of the set B or C) of the layer n.

[0206] Preferably, a base layer n+1 is superimposed on a base layer n so that the direction LAI (in particular LB1 or LC1) and the direction LA2 (in particular LB2 or LC2) of the layer n+1 are substantially parallel respectively to the direction LAI (in particular LB1 or LC1) and to the direction LA2 (in particular LB2 or LC2), of a set A (in particular of a set B or C), of the layer n.

[0207] In a variant, the base layer further comprises a set C comprising a layer of several elongate elements C1, spaced from each other, and oriented in a longitudinal direction LC1 and a layer of several elongate elements C2, spaced from each other, and oriented in a longitudinal direction LC2, the directions LC1 and LC2 being intersecting, the set C is superimposed at least in part on the set B, in particular the direction LC1 is intersecting with the direction LB1.

[0208] The variants, embodiments according to a first aspect of the invention apply independently of each other to the second aspect of the invention.

[0209] The present invention also relates, according to a third aspect, to a method for ex-vivo manufacturing of an implantable device for the replacement and / or reconstruction and / or for increasing a volume of soft tissue comprising: - the provision of an implantable device according to any one of the variant embodiments with reference to the first aspect of the invention or obtained by the manufacturing method according to a second aspect of the invention, said basic structure comprises a determined porous volume, and

[0210] - the arrangement, at least in part in said porous volume of the basic structure, of cells chosen from adipocytes, cells capable of differentiating into adipocytes and mixtures of these two types of cells, said cells preferably originating from said subject.

[0211] Preferably, adipocytes are understood to mean all cells from the adipocyte lineage, from the mesenchymal stem cell to the mature adipocyte, including all intermediate stages such as pre-adipocytes for example.

[0212] In one embodiment, the fatty tissue, in particular cells chosen from adipocytes, cells capable of differentiating into adipocytes and mixtures of these two types of cells, said cells preferably originating from said subject, is / are mixed with one or more functional agent(s) as described in the present text, in particular with reference to the first aspect of the invention chosen from list I and / or list III and / or list IV.

[0213] This arrangement makes it possible to improve the cellular response, in particular when the implantable device is intended for the treatment of a hypodermal defect.

[0214] The variant embodiments, as well as the definitions and embodiments according to a first aspect of the invention, can be combined with each other independently of each other, and with the variants according to a second aspect and / or a third aspect of the invention.

[0215] The present invention relates, according to a fourth aspect, to an implantable device obtained by implementing a manufacturing method as described with reference to the second aspect of the invention or to the third aspect of the invention.

[0216] Description of the drawings

[0217] The invention will be better understood on reading the following description of examples of embodiments of the invention given as non-limiting examples, with reference to the appended drawings, in which:

[0218] - [Fig. 1] Figure 1 schematically represents, seen from above, a first example of assembly A according to the invention;

[0219] - [Fig. 2] Figure 2 schematically represents, seen from the side, the first example of assembly A according to the invention;

[0220] - [Fig. 3] Figure 3 schematically represents a first example of superposition of sets A, B and C for the formation of a first example of base layer according to the invention;

[0221] - [Fig. 4] Figure 4 schematically represents a second example of a base layer according to the invention; - [Fig. 5] Figure 5 schematically represents an isometric view of the second example of a base layer shown in Figure 4;

[0222] - [Fig. 6] Figure 6 schematically represents a front view of the second example of base layer shown in Figures 4 and 5;

[0223] - [Fig. 7] Figure 7 schematically represents a side view of the second example of base layer shown in Figures 4, 5 and 6;

[0224] - [Fig. 8] Figure 8 is a photograph obtained by tomography, seen from above, of a first example of an implantable device according to the invention;

[0225] - [Fig.9] Figure 9 is a tomographic image, perspective view, of the first example of an implantable device shown in Figure 8;

[0226] - [Fig. 10] Figure 10 is a top view photograph of an enlarged portion of the first example of an implantable device shown in Figures 8 and 9;

[0227] - [Fig.11] Figure 11 is a tomographic image, seen in perspective and from above, of the first example of an implantable device shown in Figures 8 to 10;

[0228] - [Fig. 12] Figure 12 is a graph representing the distribution (% in number) of pores according to their sizes in the basic structure of the first example of implantable device shown in photographs 8 and 9;

[0229] - [Fig. 13] Figure 13 is a photograph of a histological section after two months of subcutaneous implantation in rats of the first example of implantable device shown in photographs 8 to 11;

[0230] - [Fig. 14] Figure 14 is a photograph of a portion of the first example of an implantable device representing angiogenesis using the model of the chicken Chorioallantoic Membrane;

[0231] - [Fig. 15] Figure 15 is a graph representing on the ordinate the Young's modulus (kPa) measured for a volume of adipose tissue and the Young's modulus measured (kPa) for the first example of an implantable device.

[0232] Description of the embodiments

[0233] Figure 1 schematically represents a first example of an assembly IA comprising a layer of several elongated elements 1A1, spaced from each other by a distance d iAi, and oriented in a longitudinal direction LAI, as well as a layer of several elongated elements 1A2, spaced from each other by a distance d iA2, and oriented in a longitudinal direction LA2, the directions LAI and LA2 being intersecting, in particular form between them an angle of between 85° and 95°, in particular of approximately 90°. The elongate elements 1A1 are substantially parallel to each other. Similarly, the elongate elements 1A2 are substantially parallel to each other. The elongate elements 1A2 are extruded and deposited by being superimposed in a layer on the layer of elongate elements 1A1. The elongate elements 1A2 are thus integral with the elongate elements 1A1 by means of thermofused polymer portions 5, shown in FIG. 2, originating from the elongate elements 1A2 and / or the elongate elements 1A1. When depositing the elongated elements 1A2, the elongated elements 1A1 were previously extradited and deposited in an aligned manner on a support, in particular a non-stick one.

[0234] Figure 3 schematically represents the superposition of an assembly IB on the assembly IA represented in Figures 1 and 2, the assembly IB being pivoted relative to the assembly IA by an angle λ1 formed between the directions LAI and LB1, in particular between 30° and 40°, for example of the order of 36°. Figure 3 also schematically represents the superposition of an assembly IC on the assembly IB, the assembly IC being pivoted relative to the assembly IB by an angle λ2 formed between the directions LB1 and LC1, in particular between 30° and 40°, for example of the order of 36°. The assemblies IA, IB and IC thus superimposed form a base layer 10 according to the invention.

[0235] As shown in Figure 3, the set IB comprises a layer of several elongate elements 1B1 extruded, spaced from each other by a distance d iBi, and oriented in a longitudinal direction LB1 and a layer of several elongate elements 1B2 extruded, spaced from each other by a distance di B2 , and oriented in a longitudinal direction LB2, the directions LB1 and LB2 being intersecting, in particular form between them an angle of between 85° and 95°, in particular of approximately 90°. The elongate elements 1B1 are substantially parallel to each other. Likewise, the elongate elements 1B2 are substantially parallel to each other.

[0236] Similarly, the set IC comprises a layer of several elongate elements ICI, spaced from each other by a distance dici, and oriented in a longitudinal direction LC1 and a layer of several elongate elements 1C2, spaced from each other by a distance di C2, and oriented in a longitudinal direction LC2, the directions LC1 and LC2 being intersecting, in particular form an angle between them of between 85° and 95°, in particular of approximately 90°. The elongate elements ICI are substantially parallel to each other. Similarly, the elongate elements 1C2 are substantially parallel to each other.

[0237] Advantageously, the elongate elements (1A1, 1A2, 1B1, 1B2, 1C1, 1C2) are deposited according to the arrangement described above so as to form a base layer just after their extrusion so that they adhere to each other by means of thermofused portions acting as bonding points. Preferably, an upper base layer (for example an n+1 layer) is superimposed on a lower base layer (for example an n layer) so that the elongate elements A1 and A2 of the upper layer are substantially parallel respectively to the elongate elements A1 and A2 of the lower layer. Preferably, an n+1 base layer is similar to an n base layer, i.e. concerning the composition of the elongate elements, and their stacking with each other.

[0238] Figure 4 shows a second example of a base layer 20 according to the invention, which is a variant of the first example of the base layer 10 whose stack is shown in Figure 3. The second example of the base layer 20 differs from the first example 10 in that the elongate elements (2A1, 2A2, 2B1, 2B2, 2C1, 2C2) of the base layer 20 have a sinusoidal or zigzag trajectory arranged so that they comprise alternating troughs and peaks, such as the peaks 2Ala and the troughs 2Alb shown for the elongate elements 2A1. This arrangement makes it possible to improve the flexibility of the base layer 20.Advantageously, the elongate elements (for example 2A2 or 2B2 or 2C2) of an upper layer of a given assembly (for example 2A or 2B or 2C) are superimposed with the elongate elements (for example 2A1 or 2B1 or 2C1) of the lower layer of said given assembly (for example 2A or 2B or 2C) so that the hollows, respectively the peaks, of the elongate elements of the upper layer cooperate with the peaks, respectively the hollows, of the lower layer. This arrangement makes it possible to improve the blocking and the maintenance of the elongate elements between them, and makes it possible to improve the mechanical resistance of the basic structure (i.e. the maintenance of the structure in the face of mechanical stresses before implantation and after implantation).

[0239] Figure 5 represents an isometric view of the unit base layer 20 in which the three directions of space (X, Y, Z) are represented with equal importance.

[0240] Figure 6 schematically represents a front view of the unitary base layer 20.

[0241] Figure 7 shows a side view of the base layer 20 having a thickness eb of the order of 1.2 mm. Figure 8 is a photograph showing a first example of an implantable device 100 according to the invention comprising a base structure 110 comprising several base layers superimposed until the desired final thickness is obtained.

[0242] Figures 9 and 11 are also tomographic images of the implantable device 100. When taking tomographic images, radiation (X-rays) is transmitted along a beam through the implantable device 100 placed between the beam source and a detector. The distribution of matter within the object is described by the beam attenuation and spatial variables. The resolution used for analyzing the implantable device 100 is 33 microns.

[0243] In this specific example, the base structure 110 has a thickness measured between its first and second opposite faces of the order of 5 mm. The base structure 110 comprises 3 base layers 20 stacked without rotation between them. The elongated elements of the base structure 110 are extruded from a copolymer of E-caprolactone and lactic acid of L form, the mass fraction in repeating units based on E-caprolactone is approximately 30% and the mass fraction in repeating units of lactic acid is approximately 70%. The porosity of the base structure 110 is approximately 94.5%. The density is approximately 0.04 g / cm 3 .

[0244] The base layers may be, for example, base layers 10 or 20. The final thickness of the base structure 110 may be adjusted by adding an A set, or an additional A set and B set.

[0245] As seen in Figures 8-11, the base structure includes numerous open and connected pores extending between its first and second opposing faces, such as pores 112 and 114.

[0246] As can be seen in Figure 10, the base structure 110 comprises portions of elongate elements, for example chosen from the elongate elements 1A1, 1A2, 2A1, 2A2, 1B1, 1B2, 2B1, 2B2, ICI, 1C2, 2C1 or even 2C2, having a diameter dl20 or a width of the order of 0.20 mm.

[0247] Figure 11 represents the distribution (%) of surface size (mm 2 ) pores of the base structure 110, in particular comprising stacked base layers 20.

[0248] Figure 12 represents a surface in mm 2 because the pore size is measured in a plane. Considering that said pore has a substantially circular size, by the formula 2*Pi*Radius 2, we find the diameter (mm).

[0249] It is noted that the pores having sizes corresponding to those of the "microfat", that is to say less than or equal to 1.25 mm, are the most important in number in the basic structure 110. Then, the pores corresponding to the millifat, that is to say between 1.25 mm and 2.5 mm, represent the second most important category of pores, and finally the pores corresponding to the macrofat, that is to say greater than or equal to 2.5 mm, represent the least important category of pores.

[0250] In Figure 13 of a histological layer performed on the implantable device 100 after 2 months of implantation, we observe a good adipocyte density and quality corroborated by a heterogeneity in the size of the adipocytes. The absence of space between the adipocytes and the low presence of connective tissue demonstrate the good maintenance of the adipocyte volume.

[0251] Figure 14 shows angiogenesis of the implantable device 100 tested in Figure 11. The basic structure 110 comprises portions of elongated elements 120 and pores allowing vascularization, with the formation of small blood vessels, such as the blood vessel 130, and large-caliber blood vessels, such as the blood vessel 140. Advantageously, the distribution of the pores, and their sizes, make it possible to guide the orientation of the vessels, and thus to obtain homogeneous vascularization of the adipose tissue.

[0252] Figure 15 represents, in a non-limiting manner, the Young's modulus obtained for the implantable device 100 comprising the basic structure 110 compared to the Young's modulus of adipose tissue. It is noted that these Young's moduli are similar and on average close to 10 KPa.

[0253] It would be possible to obtain an equivalent Young's modulus for an implantable device according to the invention but with elongated elements in one or more polymer(s) different from the caprolactone and lactic acid copolymer selected for the device 100.

[0254] The compression test for measuring Young's modulus was conducted according to ASTM D1621-16 "Standard Test Method for Compressive Properties of Rigid Cellular Plastics". During the test, six standardized specimens with a diameter of 60.0 mm and a height of 26.4 mm were immersed in a fixed distilled water bath placed on the lower plate of the testing machine. The bath temperature was controlled at 37 °C. The upper plate descended with a constant speed at 2.6 mm / min to compress the specimen. The cell used was 250N. The force and displacement were recorded and post-processed to obtain the elastic compression modulus.

Claims

CLAIMS 1. Bioresorbable implantable device (100), in particular for the replacement and / or reconstruction and / or augmentation of soft tissue, comprising a base structure (110) comprising at least one base layer (10, 20), said base layer comprising: - an assembly A (1A, 2A) comprising a layer of several elongate elements Al (1A1, 2A1), spaced from each other, and oriented in a longitudinal direction LAI, and a layer of several elongate elements A2 (1A2, 2A2), spaced from each other, and oriented in a longitudinal direction LA2, the directions LAI and LA2 being intersecting; - a set B (1B, 2B) comprising a layer of several elongate elements B1 (1B1, 2B1), spaced from each other, and oriented in a longitudinal direction LB1 and a layer of several elongate elements B2 (1B2, 2B2), spaced from each other, and oriented in a longitudinal direction LB2, the directions LB1 and LB2 being intersecting; - the set B (1B,2B) is superimposed at least in part on the set A (1A,2A); the direction LAI is intersecting with the direction LB1; - and in that the base structure (110) comprises several base layers (10, 20) at least partially superimposed.

2. Implantable device (100) according to claim 1, characterized in that the base layer (10, 20) comprises an assembly C (1C, 2C) comprising a layer of several elongate elements C1 (1C1, 2C1), spaced from each other, and oriented in a longitudinal direction LC1 and a layer of several elongate elements C2 (1C2, 2C2), spaced from each other, and oriented in a longitudinal direction LC2, the directions LC1 and LC2 being intersecting, the assembly C (1C, 2C) is superimposed at least in part on the assembly B (1B, 2B), in particular the direction LC1 is intersecting with the direction LB1.

3. Implantable device (100) according to either of claims 1 and 2, characterized in that the direction LAI intersects with the direction LB1 and forms at their intersection an angle λ1 greater than 10° and less than or equal to 60°.

4. Implantable device (100) according to either of claims 2 and 3, characterized in that the direction LAI intersects with the direction LC1 and forms at their intersection an angle λ3 greater than λ1 of at least 10°.

5. Implantable device (100) according to any one of claims 1 to 4, characterized in that the angle formed between the LAI direction and the LA2 direction is greater than or equal to 70° and less than or equal to 110°.

6. Implantable device (100) according to any one of claims 1 to 5, characterized in that an elongate element Al (1A1) is secured to several elongate elements A2 (1A2) by means of solidified thermofused portions (5) originating from said elongate element Al and / or from the elongate elements A2 (1A2).

7. Implantable device (100) according to any one of claims 1 to 6, characterized in that at least one elongate element Al (2A1) comprises at least one portion ail of its length in a zigzag or sinusoidal shape.

8. Implantable device (100) according to claim 7, characterized in that at least one elongate element A2 (2A2) comprises at least one portion a22 of its length in a zigzag or sinusoidal shape, said portion a22 comprising hollows spaced from each other, and in that the portion a11 of said elongate element A1 is superimposed with the portion a22 of said elongate element A2 passing through a hollow of said portion a22 in a zigzag or sinusoidal shape.

9. Implantable device (100) according to any one of claims 1 to 8, characterized in that the base structure (110) has a density greater than or equal to 0.01 g / cm 3 and less than or equal to 1 g / cm 3 .

10. Implantable device (100) according to any one of claims 1 to 9, characterized in that at least a portion of the elongate elements chosen from the elongate elements A1 (1A1, 2A1), A2 (2A1, 1A2), B1 (1B1, 2B1), and B2 (1B2, 2B2), in particular C1 (1C1, 2C1) and C2 (1C2, 2C2), are portions of monofilament yarns having a diameter or width less than or equal to 0.60 mm, preferably less than or equal to 0.40 mm.

11. Implantable device (100) according to any one of claims 1 to 10, characterized in that at least a portion of the elongate elements chosen from the elongate elements A1, A2, B1, and B2, in particular C1 and C2, comprises at least one bioresorbable copolymer comprising repeating units of E-caprolactone and repeating units of lactide of form L or D or L, D.

12. Implantable device (100) according to any one of claims 1 to 11, characterized in that the base structure (110) has a porosity greater than or equal to 90%.

13. Implantable device (100) according to any one of claims 1 to 12, characterized in that at least 40% by number of the pores of the basic structure have a size greater than or equal to 0.50 mm.

14. Method for manufacturing an implantable device (100) according to any one of claims 1 to 13, characterized in that it comprises the steps: - a step of manufacturing a base layer (110) (i), said step comprising: - a step (il) of manufacturing an assembly A comprising the deposition of several elongate elements A1 (1A1, 2A1), spaced from each other, and oriented in a longitudinal direction LAI, so as to form a layer, then the deposition of several elongate elements A2 (1A2, 2A2), spaced from each other, and oriented in a longitudinal direction LA2, so as to form a layer arranged above the previous layer comprising the elongate elements A1 (1A1, 2A1), the directions LAI and LA2 being intersecting; and - a step (i2) of manufacturing an assembly B (1B, 2B) comprising the deposition of several elongate elements B1 (1B1, 2B1), spaced from each other, and oriented in a longitudinal direction LB1, so as to form a layer, then the deposition of several elongate elements B2 (1B2, 2B2), spaced from each other, and oriented in a longitudinal direction LB2, so as to form a layer arranged above the previous layer comprising the elongated elements B1 (1B1,2B1), the directions LB1 and LB2 being intersecting; - set B (1B,2B) is superimposed at least in part on set A (1A,2A); - the LAI direction is intersecting with the LB1 direction; - and in that the implantable device (100) comprises a base structure (110) comprising several base layers (10, 20) at least partially superimposed.

15. Method for ex-vivo manufacturing of an implantable device (100) for the replacement and / or reconstruction and / or increase of a volume of soft tissue comprising: - providing an implantable device (100) according to any one of claims 1 to 13 comprising a base structure (110) comprising a determined pore volume and - the arrangement at least in part in said porous volume of the basic structure (110) of cells chosen from adipocytes, cells capable of differentiating into adipocytes and mixtures of these two types of cells, said cells preferably originating from said subject.

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