Implantable devices, especially for the reconstruction of subcutaneous tissue

Abstract

The present invention relates to a bioabsorbable implantable device (100) comprising a base structure including at least one base layer (10), said base structure comprising: an assembly A (1A) including a layer of a plurality of elongated elements A1 (1A1) and a layer of a plurality of elongated elements A2 (1A2) oriented in a longitudinal direction LA1; and an assembly B (1B) including a layer of a plurality of elongated elements B1 (1B1) and a layer of a plurality of elongated elements B2 (1B2) oriented in a longitudinal direction LB1, said assembly B (1B) being at least partially disposed on said assembly A (1A), said direction LA1 intersecting said direction LB1, said base structure comprising a plurality of base layers disposed at least partially overlapping each other.

Description

[Technical Field]

[0001] The present invention relates to an implantable device, particularly for the reconstruction of subcutaneous tissue, and to a method for manufacturing said device.

[0002] In particular, the present invention relates to an implantable device for replacing and / or reconstructing and / or augmenting an amount of soft tissue, particularly an amount of adipose tissue, after harvesting the tissue from a subject.

[0003] The amount of soft tissue taken from the subject may be, but is not limited to, a tumor, a portion of subcutaneous tissue, a portion of adipose tissue, or a portion of breast tissue, or a combination thereof. [Background technology]

[0004] The skin is the outer membrane that covers our body. It accounts for one-third of the human body's weight and covers approximately 2 m² in adults. 2 has a surface area of

[0005] The skin is a complex organ, consisting of three layers: the epidermis, dermis, and subcutaneous tissue, separated from the underlying organs by fascia.

[0006] The epidermis, or surface layer, protects the body from external aggressions. After migration of keratinocytes, the epidermis forms a multilayered, flattened and keratinized covering epithelium.

[0007] The thickness of the epidermis varies from region to region and is determined by the thickness of the stratum corneum.

[0008] The epidermis is constantly regenerating, regenerating every 21 days on average. The dermis is the tissue that supports and nourishes the epidermis. It is a complex connective tissue and, unlike the epidermis, is richly vascularized. It is thicker than the epidermis (0.5-2 mm compared to 0.1 mm), and the presence of fibrous proteins gives the skin its elasticity and firmness. The subcutaneous tissue, or subcutaneous adipose tissue, separates the dermis from the underlying muscle and bone. The subcutaneous tissue is the deepest and thickest layer of the skin. It has mechanical, aesthetic, protective, and metabolic functions and is composed of loose connective tissue containing adipocytes. Its thickness varies greatly depending on the individual, age, location, and nutritional status.

[0009] Many traumatic injuries affect the subcutaneous tissue over large areas or parts of the body, destroying or damaging it and potentially resulting in serious sequelae.

[0010] Every day, approximately 32,000 serious injuries affecting the subcutaneous tissue and resulting in serious sequelae occur worldwide. These injuries include third- and fourth-degree burns to the skin, tumor resections, frostbite, ulcers, or birth defects. These injuries can be caused by explosive devices or firearms, or by transportation or domestic accidents.

[0011] The primary approach to the reconstruction of the subcutaneous tissue is autologous skin flap transfer, i.e., vascularized full-thickness skin grafting. This surgical procedure is time-consuming, difficult, and painful for the patient, and therefore is only applicable to small wounds.

[0012] A second reconstructive approach involves the intradermal injection of non-autologous fillers (e.g., hyaluronic acid). This procedure is minimally invasive, but the injected material is not autologous and the filler is not permanent. Furthermore, this technique can only be applied to very small wounds.

[0013] A third reconstructive approach involves harvesting non-vascularized adipose tissue, processing it, and then reinjecting it into the treatment area via grafting (e.g., fat injection). This method has the advantage of being minimally invasive, but requires multiple procedures over time to achieve the desired appearance and to replace lost adipose tissue.

[0014] The harvesting and subsequent injection of adipose tissue using a small diameter cannula (typically about 4 mm) subjects cells to shear stress and abnormal pressure, reducing initial cell viability. Furthermore, damaged cells are re-injected into a restricted space where they cannot directly access nutrients and growth factors via the vascular network. As a result, the volume of adipose tissue can unpredictably decrease by up to 80%.

[0015] To date, there is no effective, fast, simple and inexpensive surgical solution for reconstructing soft tissue, especially subcutaneous tissue.

[0016] If reconstruction is not performed, patients will suffer psychological, aesthetic, and functional sequelae.

[0017] Therefore, there is a need for an implantable device for soft tissue reconstruction that is flexible, compressible, lightweight, and cuttable to specific shapes while retaining its structure, integrity, and mechanical properties.

[0018] There is also a need for a bioabsorbable implantable device that is configured to accept a predetermined amount of initial adipose tissue before implantation and to retain as much adipose tissue volume as possible after implantation without significant volume loss or the need for additional fat filling.

[0019] Additionally, there is a need for implantable devices that improve the behavior of transplanted adipose tissue with respect to cell migration and proliferation, adipocyte uptake and retention, and cell viability.

[0020] Finally, there is a need for an implantable device for soft tissue reconstruction and / or replacement and / or augmentation that facilitates the surgical procedure by avoiding the need to rework the cut ends of the implantable device, particularly after shaping the device and filling with new adipose tissue.

[0021] DISCLOSURE OF THE INVENTION According to a first aspect, the present invention relates to an implantable device, in particular a bioabsorbable device, in particular for soft tissue replacement and / or reconstruction and / or augmentation, such as subcutaneous tissue reconstruction and / or replacement or breast replacement and / or reconstruction and / or augmentation, said implantable device comprising a base structure, said base structure comprising at least one base layer, said base layer comprising: an assembly A comprising a layer of elongated elements A1 spaced apart from one another and oriented in a longitudinal direction LA1, and a layer of elongated elements A2 spaced apart from one another and oriented in a longitudinal direction LA2, wherein the directions LA1 and LA2 intersect; an assembly B comprising a layer of elongated elements B1 spaced apart from one another and oriented in a longitudinal direction LB1, and a layer of elongated elements B2 spaced apart from one another and oriented in a longitudinal direction LB2, wherein the directions LB1 and LB2 intersect; Including, said assembly B is at least partially disposed on said assembly A, in particular on said assembly A; The direction LA1 intersects with the direction LB1, The implantable device includes a base structure having a plurality of base layers disposed at least partially on top of one another.

[0022] The inventors have found that the implantable device of the present invention has numerous advantages, including improved cell migration and proliferation, easier full-thickness insertion of and enhanced retention of adipocytes within the base structure, increased initial cell viability, and reduced long-term cell death, particularly with respect to the amount of adipose tissue harvested by liposuction and introduced into the implantable device.

[0023] By stacking and arranging selected elongated elements within the framework of the present invention, open and interconnected pores of various sizes can be formed, which can receive and retain different types of fat (e.g., macrofat, millifat, microfat, and even nanofat, which are named depending on the size of the fat-collecting cannula).

[0024] The implantable device also has the advantage of facilitating surgery since it does not require reinjection of new amounts of adipose tissue to replace the initial loss of adipose tissue after implantation.

[0025] Additionally, the harvested adipose tissue can be spread to penetrate the entire thickness of the implantable device, avoiding shearing of cells during delivery and improving initial cell viability.

[0026] The implantable device also has the advantage that it can be divided without losing its cohesion, and can be adapted by cutting to the dimensions of the anatomical area to be treated, particularly the area requiring filling and / or reconstruction. The implantable device according to the present invention is also advantageous in that it can be manufactured industrially and yet can be customized.

[0027] These observed benefits were evaluated in comparison with reconstructive techniques that place only a layer of adipose tissue in the treated defect.

[0028] The implantable device according to the present invention is generally used to fill any anatomical defect containing adipose tissue, particularly non-vascularized or vascularized, preferably non-vascularized.

[0029] The implantable device is preferably suitable for subcutaneous tissue reconstruction or breast reconstruction.

[0030] Advantageously, the implantable device is configured to allow for the reconstruction and / or replacement of subcutaneous tissue and is also compatible with dermal and epidermal reconstruction techniques.

[0031] In this specification, the base structure includes n+1 base layers, where n is an integer of 1 or more.

[0032] In this specification, base layer n+1 has the same structure as base layer n.

[0033] Preferably, base layer n+1 is arranged on base layer n and is arranged such that at least one elongated element A1 (or the respective corresponding A2) of assembly A of base layer n+1 is substantially parallel to at least one elongated element A1 (or the respective corresponding A2) of assembly A of base layer n.

[0034] Preferably, the base layer n+1 is placed on the base layer n without rotating the assembly A of the layer n+1 relative to the assembly A of the layer n.

[0035] Preferably, base layer n+1 is arranged on base layer n and is arranged so that at least one elongated element A1 (particularly B1 or C1) and at least one elongated element A2 (particularly B2 or C2) of assembly A (particularly assembly B or C) of layer n+1 are substantially parallel to at least one elongated element A1 (particularly B1 or C1) and at least one elongated element A2 (particularly B2 or C2) of assembly A (particularly assembly B or C) of layer n, respectively.

[0036] Preferably, base layer n+1 is arranged on base layer n and is arranged so that the direction LA1 (particularly LB1 or LC1) and direction LA2 (particularly LB2 or LC2) of layer n+1 are substantially parallel to the direction LA1 (particularly LB1 or LC1) and direction LA2 (particularly LB2 or LC2) of assembly A (particularly assembly B or C) of layer n, respectively.

[0037] implantable devices Advantageously, the base structure has open and interconnected pores.

[0038] Thus, fat that is harvested and applied to one side of the base structure diffuses through the base structure and is retained within said base structure by the array of interconnected, open pores of different sizes.

[0039] In particular, the base structure has open pores with a size greater than 1 mm, open pores with a size between 1 μm and 1 mm, and open pores with a size between 1 μm and 1 nm.

[0040] As used herein, open and connected pores means that the pores are in fluid communication with one another.

[0041] Advantageously, the base structure, in particular the implantable device, is a plate-like body having a thickness, in particular the general shape of which depends on the end use.

[0042] Advantageously, the base structure, in particular the implantable device, can be manufactured in the form of a rectangular or square plate or any predetermined three-dimensional shape, for example a dome, from which the structure can be resized, in particular by cutting, to fit the defect to be treated.

[0043] In one embodiment, the base structure is manufactured, particularly three-dimensionally, according to a custom-made shape that corresponds specifically to the patient's defect (the predetermined shape of the base structure is said to be patient-specific).

[0044] Preferably, the base structure is manufactured by three-dimensional printing.

[0045] Thus, the base structure, and in particular the implantable device, may have any shape, such as rectangular, square, disc-shaped, or even dome-shaped.

[0046] Preferably, the base structure, in particular the implantable device, has a first surface and a second surface substantially opposite the first surface, the first surface being in fluid communication with the second surface, advantageously via open and interconnected pores.

[0047] Preferably, the base structure, and in particular the implantable device, has open and interconnected pores opening onto its first and second sides.

[0048] In one embodiment, the base structure, and in particular the implantable device, has a substantially uniform predetermined thickness, and in particular corresponds to the distance separating the first and second sides of the base structure.

[0049] For example, the base structure, in particular the implantable device, has a substantially constant thickness of 0.5 mm to 50 mm, preferably 1 mm to 20 mm, in particular for the reconstruction and / or replacement of subcutaneous tissue.

[0050] For example, the base structure (especially for the reconstruction and / or replacement of subcutaneous tissue), especially the implantable device, has a thickness of 2 mm or 3 mm or 4 mm or 4.5 mm or more, preferably 15 mm or 10 mm or 8 mm or 6 mm or 5 mm or less.

[0051] In one embodiment, the base structure, particularly the implantable device, has a variable thickness that particularly corresponds to the distance separating the first and second sides of the implantable device, e.g., the base structure, particularly the implantable device, has a generally dome-shaped configuration.

[0052] For example, the base structure, in particular the implantable device, has a variable thickness ranging from 0.5 mm to 150 mm, preferably from 0.5 mm to 65 mm, in particular for breast reconstruction and / or replacement and / or augmentation.

[0053] In particular, if the base structure is dome-shaped, the value of 65 mm corresponds to the apex of the dome.

[0054] In this specification, a value included in the range a to b means that the lower limit a and the upper limit b are included in the range.

[0055] In one example, the implantable device comprises, in particular consists essentially of, a plurality of base layers arranged on top of one another, optionally Assembly A and / or Assembly B and / or Assembly C, and optionally one or more functional agents.

[0056] In one embodiment, particularly for the reconstruction and / or replacement of subcutaneous tissue, the base structure comprises 2 to 20 base layers, particularly 3 to 20 base layers, preferably 2 to 10 base layers, more preferably 2 to 6 base layers, particularly 3 to 5 base layers, particularly 3 base layers (particularly each comprising assembly A, assembly B and assembly C), and a partial base layer essentially consisting of assembly A and / or assembly B.

[0057] In one embodiment, the base structure comprises four base layers, in particular, each base layer comprises assembly A, assembly B, and assembly C, optionally at least one of assembly A and / or assembly B and / or assembly C.

[0058] In one embodiment, the thickness of the base layer (particularly the base layer including assemblies A, B, and C) is about 0.8 mm to 1.5 mm, and preferably about 1.1 mm to ±0.1 mm.

[0059] In one embodiment, the base layer has a thickness of 0.5 mm to 1.5 mm.

[0060] In one embodiment, the base structure comprises, in particular essentially consists of, a plurality of base layers arranged on top of one another and optionally additional assemblies A and / or B and / or C.

[0061] The base layers are placed one on top of the other until the desired final thickness of the base structure, in particular for the implantable device, is obtained. The final base layer may be partial, i.e., it may contain only assembly A, or one assembly A and one assembly B, to precisely achieve the desired final thickness.

[0062] Advantageously, the base structure, and in particular the amount of adipose tissue placed within the porous space of the implantable device, is of autologous origin.

[0063] Advantageously, the base structure, and in particular the amount of adipose tissue placed within the porous spaces of the implantable device, is non-vascularized.

[0064] Advantageously, the implantable device and / or said base structure and / or at least one and / or more of the base layers, which are particularly bioabsorbable, comprise, in particular consist essentially of, one or more (co)polymers, as described herein, which are particularly bioabsorbable.

[0065] Functional Agents Advantageously, the base structure may be treated, such as impregnated or coated, with one or more functional agents.

[0066] Preferably, the functional agent is one of the following: (i) improving cell and tissue regeneration (e.g., promoting the growth, proliferation, and / or differentiation of adipocytes) and / or maintaining the extracellular matrix; and / or (ii) suppressing or inhibiting the growth of microorganisms; and / or (iii) Suppressing local inflammatory responses and preventing the progression of fibrosis The present invention is directed to any active substance for the purpose of

[0067] Preferably, the one or more functional agents are: The following: growth factors that promote angiogenesis, for example, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1 (SDF-1), any cell fraction such as platelet-rich plasma (PRP) or platelet lysate; factors that promote cell proliferation, cell migration and adipocyte differentiation, such as fibroblast growth factor (FGF) and insulin-like growth factor (IGF); corticosteroids such as dexamethasone; hormones such as insulin; therapeutic agents such as 3-isobutyl-1-methylxanthine (IBMX); stromal vascular fraction (SVF); cell adhesion-promoting factors such as fibronectin and polydopamine, and / or selected from List I, which includes (in particular consists essentially of): Cells selected from adipocytes, cells that can be differentiated into adipocytes, a mixture of cells selected from adipocytes and cells that can be differentiated into adipocytes, preferably these cells derived from the patient to be treated, or a mixture of the latter, and / or selected from List II, which comprises (in particular consists essentially of) The following: antithrombotic agents, especially anticoagulants (such as heparin), antiplatelet agents (such as aspirin), thrombolytic agents that destroy blood clots in situ; antiparasitic molecules; anti-inflammatory agents; vitamins; disinfectants (such as betadine); antibiotics; or mixtures of the latter, and / or selected from List III, which includes (in particular consists essentially of): A bioabsorbable polymer matrix is ​​formed, in particular the bioabsorbable polymer matrix is ​​a hydrogel, and preferably the functional agent is the following: cyclodextrin, cyclodextrin derivatives, gelatin, chitosan, lactic acid (co)polymers (L or D), glycolic acid (co)polymers, copolymers of lactic acid and glycolic acid, copolymers of lactic acid (L or D) or glycolic acid with caprolactone, caprolactone, poly-p-dioxanone polymers, carrageenan, collagen, or other molecules that mimic the structure and organization of the extracellular matrix, or mixtures thereof; and selected from List IV including (in particular consisting essentially of):

[0068] In one embodiment, the base structure is at least partially coated with a functional agent that forms a bioabsorbable polymer matrix, particularly selected from List IV, optionally in admixture with one or more functional agents selected from List I and / or List II and / or List III.

[0069] Preferably, the functional agent selected from List II is one or more volumes of adipose tissue at least partially disposed within the porous volume of said base structure. Preferably, said volumes of adipose tissue are autologous.

[0070] First, the implantable device has a coating in a bioabsorbable polymer matrix, particularly as described herein, optionally comprising one or more functional agents selected from List I and / or List II and / or List III, fully or partially covering at least one side of the base structure, particularly fully or partially covering the first and / or second sides of the base structure.

[0071] In a second example, optionally in combination with the first example, at least a portion of the walls of the open and connected pores are coated with a coating, particularly formed as a bioabsorbable polymer matrix as described herein, optionally the coating comprising one or more functional agents selected from List I and / or List II and / or List III, particularly the coating comprising at least a certain amount of adipose tissue.

[0072] elongate elements A1 and / or A2 and / or B1 and / or B2 and / or C1 and / or C2 (as described in the remainder of the text) Preferably, the elongate elements are part of a monofilament thread or cord, in particular extruded from a mixture comprising at least one (co)polymer.

[0073] Advantageously, therefore, at least a portion of the elongate elements selected 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 part of a monofilament yarn or cord and are in particular extruded from a mixture comprising at least one (co)polymer, in particular a (co)polymer as described herein.

[0074] Preferably, said base structure is obtained by additive manufacturing, more particularly by three-dimensional printing of elongated elements A1, B1 and C1, in particular A2, B2 and C2.

[0075] Preferably, the base structure comprises elongate elements A1 and / or A2 and / or B1 and / or B2 and / or C1 and / or C2 each comprising a portion with a diameter or width of 0.01 mm to 0.80 mm, more preferably 0.01 mm to 0.50 mm, preferably 0.01 mm to 0.30 mm, especially 0.10 mm to 0.30 mm.

[0076] Preferably, said elongate element, in particular a part of said monofilament thread or said cord, comprises, in particular consists essentially of, at least one bioabsorbable (co)polymer.

[0077] In one embodiment, at least a portion of the elongate elements selected from the elongate elements A1 (particularly 1A1, 2A1), A2 (particularly 2A1, 1A2), B1 (particularly 1B1, 2B1), and B2 (particularly 1B2, 2B2), particularly C1 (particularly 1C1, 2C1) and C2 (particularly 1C2, 2C2), comprises, particularly consists essentially of, at least one bioabsorbable (co)polymer.

[0078] The (co)polymer may be a homopolymer, or a copolymer, or a terpolymer.

[0079] Said (co)polymers may be selected from lactic acid (co)polymers (such as PLLA or PDLA, and PLA); ε-caprolactone (co)polymers; polydioxanone; glycolic acid (co)polymers (such as PLGA); (co)polymers of glycolic acid and lactic acid; and (co)polymers of lactic acid and ε-caprolactone.

[0080] Preferably, said (co)polymer comprises at least two different repeat units.

[0081] Preferably, the (co)polymer is an ε-caprolactone polymer and has at least one unit different from ε-caprolactone, for example a repeat unit derived from lactic acid and / or glycolic acid.

[0082] Preferably, the repeating unit derived from lactic acid may be an L-lactic acid repeating unit and / or a D-lactic acid repeating unit and / or a D,L-lactic acid repeating unit.

[0083] Preferably, said at least one (co)polymer comprises ε-caprolactone repeat units in a molar fraction (in said (co)polymer) of not more than 50%, more preferably not more than 40%, in particular between 20% and 40%, both limits included.

[0084] Preferably, the at least one (co)polymer contains repeating units of L-lactic acid and / or D-lactic acid and / or D,L-lactic acid, the molar fraction of which (in the (co)polymer) is 50% or more, more preferably 60% or more, and in particular 60% to 80% (both inclusive).

[0085] The mole fraction may be determined by NMR spectroscopy.

[0086] Preferably, the at least one (co)polymer comprises repeating units of L-lactic acid and / or D-lactic acid and / or D,L-lactic acid in a molar fraction of 90% or less, more preferably 80% or less.

[0087] In this specification, it is understood to mean that an element essentially consists of one or more subelements, said subelements making up at least 80% by weight or at least 80% by volume of the element, in particular at least 90% by weight or at least 90% by volume.

[0088] Advantageously, several layers of elongate elements A1 and A2 are arranged stacked on top of each other.

[0089] Advantageously, the layer of elongate elements A2 is arranged above the layer of elongate elements A1.

[0090] Advantageously, said plurality of elongate elements A1 are arranged substantially parallel to one another and spaced apart from one another.

[0091] Advantageously, a plurality of said elongate elements A2 are arranged substantially parallel to one another and spaced apart from one another.

[0092] Advantageously, several layers of elongate elements B1 and B2 are arranged stacked on top of each other.

[0093] Advantageously, the layer of elongated elements B2 is arranged above the layer of elongated elements B1.

[0094] Advantageously, said plurality of elongate elements B1 are arranged substantially parallel to one another and spaced apart from one another.

[0095] Advantageously, said elongate elements B2 are arranged substantially parallel to one another and spaced apart from one another.

[0096] Advantageously, said assembly B is placed above said assembly A at an angle of rotation corresponding to the angle formed by the intersection of the directions LA1 and LB1.

[0097] The rotation angle is measured clockwise and is therefore opposite to the trigonometric direction.

[0098] This arrangement allows for the creation of open and interconnected pores of various sizes and shapes.

[0099] In another embodiment, the base layer comprises an assembly C including a layer of elongated elements C1 spaced apart from one another and oriented in a longitudinal direction LC1 and a layer of elongated elements C2 spaced apart from one another and oriented in a longitudinal direction LC2, the directions LC1 and LC2 intersecting, and the assembly C is at least partially arranged on the assembly B, in particular the direction LC1 intersecting with the direction LB1.

[0100] It was also observed that the base layer could be vascularized through interconnected pores from assembly A to assembly C. Thus, vascularization was observed throughout the thickness of the base structure.

[0101] Advantageously, the three assemblies A, B, and C can be placed one on top of the other to form an array of open and connected pores with a greater variety of sizes, facilitating soft tissue reconstruction.

[0102] Advantageously, the layers of elongate elements C1 and C2 are arranged one on top of the other.

[0103] Advantageously, the layer of elongate elements arranged at least partially on C2 is arranged on top of the layer of elongate elements C1.

[0104] Advantageously, said elongate elements C1 are arranged substantially parallel to one another and spaced apart from one another.

[0105] Advantageously, said elongate elements C2 are arranged substantially parallel to one another and spaced apart from one another.

[0106] Advantageously, said assembly C is placed above said assembly B at a rotation angle corresponding to the angle formed by the intersection of said direction LB1 and said direction LC1.

[0107] In another embodiment, the direction LA1 intersects with the direction LB1 and forms an angle λ1 at the intersection of 10° to 60°, in particular 20° to 45°, in particular 30° to 40°, for example around 36°.

[0108] In another embodiment, the assembly B is placed above the assembly A rotated by the angle λ1.

[0109] Advantageously, said elongate element B1 is rotated by said angle λ1 relative to said elongate element A1.

[0110] In another embodiment, the direction LA1 intersects with the direction LC1 and forms an angle λ3 at the intersection that is at least 10° greater than λ1, in particular about twice λ1. Preferably, λ3 is between 40° and 90°, more preferably between 60° and 80°.

[0111] Advantageously, the assembly C is arranged on the assembly B rotated by an angle λ2 of at least 10°. Preferably, the angle λ2 is between 10° and 60°, in particular between 20° and 45°, in particular between 30° and 40°, for example around 36°. Preferably, the angle λ2 is substantially equal to λ1.

[0112] Advantageously, said assemblies A, B and C are not arranged one above the other in the base layer such that said elongate elements A1, B1 and C1 are aligned in parallel directions.

[0113] This arrangement of the assemblies A, B and C on top of one another allows the layers of elongate elements (A1, A2, B1, B2, C1, C2) to be fixed together and also increases the contact area between these layers, which, without such rotation, results in conduits of perfectly reproducible shape.

[0114] This arrangement has also been observed to favorably contribute to the placement and orientation of blood vessels in the base layer through the interconnected pores from Assembly A to Assembly C. Thus, vascularization is favorably observed throughout the thickness of the base structure.

[0115] In another embodiment, the angle formed between the direction LA1 and the direction LA2 is 70° to 110°, in particular 80° to 100°, more particularly 85° to 95°, in particular about 90°.

[0116] In another embodiment, the angle formed between said direction LB1 and said direction LB2 is ≧70° and ≦110°, in particular 80°-100°, more in particular 85°-95°, in particular about 90°.

[0117] In another embodiment, the angle formed between the direction LC1 and the direction LC2 is 70° to 110°, in particular 80° to 100°, more particularly 85° to 95°, in particular about 90°.

[0118] In another embodiment, in the layer of multiple elongated elements A1, A2 of the assembly A, the spacing between two adjacent elongated elements A1 or two adjacent elongated elements A2 is 2 mm to 8 mm, preferably 3 mm to 6 mm, more preferably 3.5 mm to 4.5 mm, and in particular about 4 mm.

[0119] This configuration allows the size of the open pores to be adjusted to achieve an appropriate compromise for retaining both small cell aggregates (e.g., microfat) and larger cell aggregates (e.g., macrofat).

[0120] This spacing has also been found to promote good penetration, distribution and retention of adipose tissue throughout the thickness of the base structure.

[0121] In another embodiment, in the layer of multiple elongated elements B1 and B2 of assembly B, the spacing between two adjacent elongated elements B1 or between two adjacent elongated elements B2 is 2 mm to 8 mm, preferably 3 mm to 6 mm, more preferably 3.5 mm to 4.5 mm, and in particular about 4 mm.

[0122] In another embodiment, in the layer of multiple elongated elements C1 and C2 of the assembly C, the spacing between two adjacent elongated elements C1 or between two adjacent elongated elements C2 is 2 mm to 8 mm, preferably 3 mm to 6 mm, more preferably 3.5 mm to 4.5 mm, and in particular about 4 mm.

[0123] In another embodiment, at least one elongate element A1 is secured to the plurality of elongate elements A2 by a solidified heat melt arising from said elongate element A1 and / or said elongate element A2.

[0124] The elongated element A2 is placed on top of the elongated element A1 in a partially softened state, and the elongated element A1 is also in a partially softened state and is positioned so that they adhere to each other at their intersections, thereby forming anchor points between the element A1 layer and the element A2 layer.

[0125] This configuration improves the cohesion and tear resistance of the base structure, allowing it to be cut to desired dimensions without damaging the structure.

[0126] In another embodiment, at least one elongate element B1 is secured to the plurality of elongate elements B2 by solidified heat seals originating from the elongate element B1 and / or the elongate element B2.

[0127] In another embodiment, at least one elongate element C1 is secured to the plurality of elongate elements C2 by solidified heat seals originating from the elongate element C1 and / or the elongate element C2.

[0128] In another embodiment, at least one elongate element A1 has a zigzag or sinusoidal shape over at least a portion a11 of its length.

[0129] Advantageously, said portion a11 includes a valley and a peak.

[0130] Such a configuration can improve the flexibility and therefore the deformation capacity of the assembly A, and therefore of the base layer and ultimately of the base structure.

[0131] Advantageously, at least one elongate element A2 has, for at least a portion a22 of its length, a zigzag or sinusoidal shape, in particular including valleys and peaks.

[0132] Advantageously, at least one elongate element B1 has, for at least a portion b11 of its length, a zigzag or sinusoidal shape, in particular including valleys and peaks.

[0133] Advantageously, at least one elongate element B2 has, for at least a portion b22 of its length, a zigzag or sinusoidal shape, in particular including valleys and peaks.

[0134] Advantageously, at least one elongate element C1 has, for at least a portion c11 of its length, a zigzag or sinusoidal shape, in particular including valleys and peaks.

[0135] Advantageously, at least one elongate element C2 has, for at least a portion C22 of its length, a zigzag or sinusoidal shape, in particular including valleys and peaks.

[0136] In another embodiment, at least one elongate element A2 has a zigzag or sinusoidal shape over at least a portion a22 of its length, said portion a22 including spaced apart valleys, and portion a11 of said elongate element A1 is disposed over said portion a22 of said elongate element A2 such that it passes through the valleys of said zigzag or sinusoidal shape of said portion a22.

[0137] This configuration allows the layers of elongate elements to be stacked without movement between them, providing stability to the base structure.

[0138] In the aforementioned variants, preferably zigzag or sinusoidal sections are formed repeatedly over the entire length of the elongate elements, in particular A1 and / or A2 and / or B1 and / or B2 and / or C1 and / or C2.

[0139] In one variant, at least one elongated element A1, B1 or C1 has at least one sinusoidal or zigzag portion including valleys and peaks, and at least one elongated element A2, B2 or C2 has at least one sinusoidal or zigzag portion including valleys and peaks, and said at least one elongated element A1, B1 or C1 is arranged above said at least one elongated element A2, B2 or C2, so that the valleys and peaks of said at least one elongated element A1 cooperate with the peaks and valleys of said at least one elongated element A2, respectively.

[0140] In another embodiment, the density of the base structure is 0.01 g / cm 3 More than 1g / cm 3 or less, preferably 0.1 g / cm 3 or less, more preferably 0.05 g / cm 3 The following is the result.

[0141] In one variant, at least a portion of the elongate elements A1, A2, B1 and B2, in particular selected from C1 and C2, are portions of monofilament thread having a diameter or width of 0.60 mm or less, preferably 0.40 mm or less, in particular 0.10 mm to 0.30 mm, in particular around 0.20 mm.

[0142] In another embodiment, the base structure comprises open and connected micropores, open and connected millipores, and open and connected macropores.

[0143] In this specification, micropores refer to pores having at least one dimension less than or equal to 1.2 mm, in particular in the range of 0.1 mm to 1.2 mm.

[0144] The size of the micropores of the base structure is advantageously adapted to accommodate cell aggregates corresponding to the so-called microfat category, which are collected with a cannula having an internal diameter of 1.2 mm or less, preferably 0.1 mm or more.

[0145] In this specification, millipores are understood to mean pores having at least one dimension less than or equal to 2.4 mm, in particular in the range from 1.2 mm to 2.4 mm.

[0146] The size of the millipores of said base structure is advantageously adapted to accommodate cell aggregates corresponding to the category called millifat category, which are collected with cannulas having an internal diameter of 2.4 mm or less, preferably 1.2 mm or more.

[0147] In this specification, macropores are understood to mean pores having at least one dimension greater than 2.4 mm, in particular pores ranging from 2.4 mm to 10 mm.

[0148] The size of the macropores of the base structure is advantageously adapted to accommodate cell aggregates corresponding to the category called macrofat category, which are collected with cannulas having an internal diameter of more than 2.4 mm, preferably 4 mm or more, and even more preferably 10 mm or less.

[0149] It is thus observed that the base structure advantageously comprises micropores, millipores and macropores adapted to accommodate cell aggregates of different sizes depending on the different internal diameters of the cannula for harvesting the fat cells.

[0150] In another embodiment, at least 50% of the open pores in said base structure have at least one dimension less than or equal to 1.25 mm.

[0151] In another embodiment, at least 10% of the open pores in said base structure have at least one dimension greater than or equal to 1.25 mm.

[0152] In another embodiment, at least 10% of the open pores in said base structure have at least one dimension that is greater than or equal to 1.25 mm and less than or equal to 2.5 mm.

[0153] In another embodiment, at least 5% of the open pores in said base structure have at least one dimension greater than or equal to 2.5 mm.

[0154] In another embodiment, the base structure is composed of pores with a diameter of 1.25 mm or less (particularly 0.5 mm or more) in a range of 50% to 65%, pores with a diameter of 1.25 mm to 4 mm in a range of 25% to 45%, and pores with a diameter of 4 mm or more in a range of 5% to 10%.

[0155] In one variant, at least 40%, preferably at least 60%, more preferably at least 80% by number of pores in said base structure have a size of 0.5 mm or greater.

[0156] Preferably, the method for determining the pore size and number distribution (%) comprises the following steps: - Observe and take images using binoculars with a 10x objective lens equipped with an apparent ruler, especially from above; -For each test, measure the size of approximately 100 pores on the sample and repeat at least three times; -Upload to ImageJ1.53t software; -Define the image as 8-bit using the "Image > Type > 8-bit" tool; - Use the "Analysis>Set Scale" tool to define the scale by referring to the ruler in the field of view; - Binarize the image using the "Image > Adjust > Threshold" tool; - Highlight pores according to threshold changes; - "Analyze>Analyze particles" - Size (pixels) 2 ):2-∞, circularity [0.00-1.00] and check the "exclude on edges" box; - Save generated tables in CSV format; -Upload the table to Excel and split the information into "count", "area", and "mean" columns; -Calculate the class distribution -Determine the proportion of each class.

[0157] Preferably, the pore size is measured by cross-sectional optical microscopy of the base structure or the implantable device (i.e., measured in two dimensions), and in particular is calculated as an average of about 100 measurements along each of the three axes X, Y, and Z (in particular, each axis corresponding to the 3D printing of the base structure).

[0158] Pore ​​size can be measured on the raw base structure or on the base structure containing one or more functional agents.

[0159] In one variant, at least a portion of the elongate elements A1, A2, B1 and B2, in particular selected from C1 and C2, comprises, in particular essentially consists of, at least one bioabsorbable (co)polymer, preferably comprising repeating units of ε-caprolactone and repeating units of L- or D- or L,D-lactide.

[0160] The copolymer can be expressed in the form of poly(L-lactide or D-lactide or L,D-lactide-co-ε-caprolactone), in particular poly(L-lactide-co-ε-caprolactone).

[0161] In one variant, the bioabsorbable (co)polymer has a number average molecular weight Mn of 10,000 g / mol or more, preferably 25,000 g / mol or more, more preferably 45,000 g / mol or more, in particular 65,000 g / mol or more.

[0162] In one variant, the bioabsorbable (co)polymer has a number average molecular weight Mn of 200,000 g / mol or less, preferably 175,000 g / mol or less, more preferably 150,000 g / mol or less, in particular 120,000 g / mol or less or 100,000 g / mol or less.

[0163] In one variant, the bioabsorbable (co)polymer has a weight average molecular weight Mw of 50,000 g / mol or more, preferably 75,000 g / mol or more, more preferably 100,000 g / mol or more, in particular 125,000 g / mol or more.

[0164] In one variant, the bioabsorbable (co)polymer has a number average molecular weight Mw of 300,000 g / mol or less, preferably 275,000 g / mol or less, more preferably 250,000 g / mol or less, in particular 225,000 g / mol or less or 200,000 g / mol or less.

[0165] In one variation, the polydispersity index of the at least one bioabsorbable (co)polymer is no greater than 2.5, no greater than 2.3, or no greater than 2.1.

[0166] In one variation, the polydispersity index (I=Mw / Mn) of the bioabsorbable (co)polymer is 1 or greater, 1.3 or greater, or 1.5 or greater.

[0167] In one variant, at least a portion, or essentially all, of the elongate elements A1, A2, B1 and B2, in particular selected from C1 and C2, comprise at least one bioabsorbable (co)polymer, said at least one (co)polymer being one of the following: - repeat units of ε-caprolactone in a molar fraction (in said (co)polymer) of not more than 50%, more preferably not more than 40%, in particular in the range from 20% to 40%, and / or - the molar fraction (in the (co)polymer) of L-lactic acid repeating units and / or D-lactic acid repeating units and / or D,L-lactic acid repeating units is 50% or more, more preferably 60% or more, in particular in the range of 60% to 80%, Includes.

[0168] In another embodiment, at least a portion, or essentially all, of the elongate elements selected from the elongate elements A1, A2, B1 and B2, in particular C1 and C2, comprise, in particular consist essentially of, at least one bioabsorbable (co)polymer having an elongation at break (%) of 50% or more, preferably 100% or more, more preferably 150% or more, even more preferably 200% or more, measured in a three-dimensional direction of the specimen to be tested, in particular in the printing direction X or Y.

[0169] In one embodiment, the bioabsorbable (co)polymer has an elongation at break (%) of 2000% or less, preferably 1500% or less, more preferably 1200% or less, particularly measured along the printing direction X or Y in the three dimensions of the specimen being tested.

[0170] In one embodiment, the bioabsorbable (co)polymer has a Young's modulus of 50 MPa or more, preferably 75 MPa or more, in particular 100 MPa or more (preferably independent of the three-dimensional printing directions X, Y, Z of the specimen being tested).

[0171] In one embodiment, the bioabsorbable (co)polymer has a Young's modulus of 800 MPa or less, in particular 600 MPa or less (preferably independent of the three-dimensional printing directions X, Y, Z of the specimen to be tested).

[0172] The Young's modulus and elongation at break are measured according to ASTM D638-14 ("Standard Test Method for Tensile Properties of Plastics") using a Type V test specimen at a tensile speed of 10 mm / min, preferably at a temperature of 20° C. The test specimen is preferably manufactured by an additive manufacturing method, in particular the printing direction can vary along the X-axis, Y-axis or Z-axis.

[0173] In one variation, the base structure has a porosity of 90% or greater.

[0174] Preferably, the porosity is determined by the following formula: (total volume of base structure-void volume of base structure) / total volume of base structure×100.

[0175] Preferably, the total and actual volumes of the base structure are estimated using the SOLIDWORKS 2019-SPO4 design software (steps for use: 1 / "evaluate" tab, 2 / selection of surface, 3 / "measurement" option, 4 / surface values).

[0176] In another embodiment, the implantable device, in particular the base structure, has a Young's modulus of 5 KPa or more, preferably 80 KPa or less, more preferably 5 KPa to 60 KPa, in particular 5 KPa to 50 KPa, such as 5 KPa to 25 KPa, or around 10 KPa (±5 KPa).

[0177] The Young's modulus is advantageously measured in accordance with ASTM D1621-16 "Standard Test Method for Compressive Properties of Rigid Cellular Plastics", under the conditions described in particular with reference to FIG.

[0178] According to a second aspect, the present invention provides a method for manufacturing an implantable device, in particular according to any one of the variants relating to the first aspect of the invention, said method comprising: Step (i) of producing a base layer, said step (i) comprising: - a step (i1) of manufacturing an assembly A, comprising stacking a plurality of elongated elements A1, in particular extruded, spaced apart and oriented in a longitudinal direction LA1, to form a layer, and then stacking a plurality of elongated elements A2, in particular extruded, spaced apart and oriented in a longitudinal direction LA2, to form a layer arranged on top of the previous layer comprising said elongated elements A1, said direction LA1 and said direction LA2 intersecting; a step (i2) of manufacturing an assembly B, comprising stacking a plurality of elongated elements B1, in particular extruded, spaced apart and oriented in a longitudinal direction LB1, to form a layer, and then stacking a plurality of elongated elements B2, in particular extruded, spaced apart and oriented in a longitudinal direction LB2, to form a layer arranged on top of the previous layer comprising said elongated elements B1, said direction LB1 and said direction LB2 intersecting; Step (i) comprising: said assembly B is disposed at least partially above said assembly A; The direction LA1 intersects with the direction LB1, wherein the implantable device comprises a base structure including a plurality of base layers disposed at least partially on top of one another.

[0179] In one embodiment, the method comprises: a step (i3) of manufacturing an assembly C, comprising: depositing a plurality of elongated elements C1 spaced apart from one another and oriented in a longitudinal direction LC1 to form a layer; and then depositing a plurality of elongated elements C2 spaced apart from one another and oriented in a longitudinal direction LC2 to form a layer disposed on top of the previous layer comprising elongated elements C1, wherein the directions LC1 and LC2 intersect; Including, said assembly C being at least partially disposed above said assembly B; The direction LC1 intersects with the direction LB1.

[0180] In one example, the implantable device comprises, in particular consists essentially of, multiple base layers arranged on top of one another, and optionally Assembly A and / or Assembly B and / or Assembly C, and optionally one or more functional agents.

[0181] Advantageously, the method comprises sequentially performing a plurality of steps (i) and, optionally, then performing step (i1) or performing step (i2) after performing step (i1) until a desired thickness of the base structure is obtained.

[0182] In one variation, the implantable device includes a plurality of base layers n+1, where n is an integer greater than or equal to 1.

[0183] In one variant, the base layer n+1 is arranged on the base layer n such that at least one elongated element A1 (or respectively A2) of the assembly A of the base layer n+1 is substantially parallel to at least one elongated element A1 (or respectively A2) of the assembly A of the base layer n.

[0184] Preferably, base layer n+1 is placed on base layer n without rotating assembly A (or B or C, respectively) of said layer n+1 relative to assembly A (or B or C, respectively) of layer n.

[0185] Preferably, the base layer n+1 is arranged on the base layer n such that at least one elongated element A1 (particularly B1 or C1) and at least one elongated element A2 (particularly B2 or C2) of the assembly A (particularly assembly B or C) of the layer n+1 are substantially parallel to at least one elongated element A1 (particularly B1 or C1) and at least one elongated element A2 (particularly B2 or C2) of the assembly A (particularly assembly B or C) of the layer n, respectively.

[0186] Preferably, base layer n+1 is arranged on base layer n so that the direction LA1 (particularly LB1 or LC1) and direction LA2 (particularly LB2 or LC2) of layer n+1 are substantially parallel to the direction LA1 (particularly LB1 or LC1) and direction LA2 (particularly LB2 or LC2) of assembly A (particularly assembly B or C) of layer n, respectively.

[0187] In one variant, the base layer further comprises an assembly C including a layer of elongated elements C1 spaced apart from one another and oriented in a longitudinal direction LC1 and a layer of elongated elements C2 spaced apart from one another and oriented in a longitudinal direction LC2, the directions LC1 and LC2 intersecting, and the assembly C is at least partially arranged on the assembly B, in particular the direction LC1 intersecting with the direction LB1.

[0188] The variations and embodiments of the first aspect of the present invention are each independently applicable to the second aspect of the present invention.

[0189] The present invention also relates, according to a third aspect, to a method for manufacturing ex vivo an implantable device for replacing and / or reconstructing and / or augmenting an amount of soft tissue, said method comprising the steps of: providing an implantable device according to any one of the variants according to the first aspect of the invention or an implantable device obtained by a manufacturing method according to the second aspect of the invention, wherein the base structure has a predetermined porous volume; and disposing, at least partially within the porous volume of the base structure, cells selected from adipocytes, cells capable of differentiating into adipocytes, and a mixture of these two types of cells, wherein the cells are preferably derived from the subject; Includes.

[0190] Preferably, adipocytes are understood to refer to all cells of the adipocyte lineage from mesenchymal stem cells to mature adipocytes, including all intermediate stages such as, for example, preadipocytes.

[0191] In one embodiment, the adipose tissue, in particular cells (preferably derived from a subject) selected from adipocytes, cells capable of differentiating into adipocytes, and mixtures of these two types of cells, are mixed with one or more functional agents described herein, in particular selected from List I and / or List III and / or List IV with respect to the first aspect of the invention.

[0192] This arrangement can improve cellular response, especially when the implantable device is intended to treat a subcutaneous defect.

[0193] The variants and definitions and embodiments according to the first aspect of the invention can be combined independently of each other and can also be combined with variants according to the second and / or third aspect of the invention.

[0194] According to a fourth aspect, the present invention relates to an implantable device obtainable by carrying out the manufacturing method described with respect to the second aspect of the invention or the third aspect of the invention. [Brief explanation of the drawings]

[0195] [Figure 1] 1 shows a first example of an assembly A according to the invention, diagrammatically in top view. [Figure 2] 1 shows a first example of an assembly A according to the invention, diagrammatically in side view. [Figure 3] 1 shows a first example of assemblies A, B and C placed one on top of the other to form a first example of a base layer according to the present invention. [Figure 4] 2 shows a schematic representation of a second example of a base layer according to the present invention; [Figure 5] 5A and 5B show schematic isometric views of a second example of the base layer shown in FIG. 4; [Figure 6] FIG. 6 shows a schematic front view of a second example of the base layer shown in FIGS. 4 and 5; [Figure 7] 7 shows a schematic side view of a second example of the base layer shown in FIGS. 4, 5 and 6; FIG. [Figure 8] 1 is a top-view tomographic photograph of a first example of an implantable device according to the present invention. [Figure 9] 9 is a cross-sectional photograph showing a perspective view of the first example of the implantable device shown in FIG. 8. [Figure 10] 10 is a top view photograph of a portion of the first example of the implantable device shown in FIGS. 8 and 9, enlarged. [Figure 11] 11A-11C are cross-sectional photographs showing a perspective view and a top view of the first example of the implantable device shown in FIGS. 8-10. [Figure 12] 10 is a graph showing the distribution (by number %) of pores by size in the base structure of the first example of the implantable device shown in Photos 8 and 9. [Figure 13] This is a photograph of a tissue section taken two months after the first example of the implantable device shown in Photos 8 to 11 was subcutaneously implanted into a rat. [Figure 14] 1 is a photograph of a portion of a first example of an implantable device demonstrating angiogenesis using a chick chorioallantoic membrane model. [Figure 15] 1 is a graph showing Young's modulus (kPa) measured against the volume of adipose tissue on the vertical axis and Young's modulus (kPa) measured for a first example of an implantable device. DETAILED DESCRIPTION OF THE INVENTION

[0196] FIG. 1 shows a first example of an assembly 1A comprising a layer of a plurality of elongated elements 1A1 and a layer of a plurality of elongated elements 1A2, the elongated elements 1A1 being spaced apart from one another by a distance d 1A1 and oriented in the longitudinal direction LA1, the elongated elements 1A2 are spaced apart by a distance d 1A2 The elongate elements 1A1 are spaced apart by a distance .05 mm and oriented in a longitudinal direction LA2. The directions LA1 and LA2 intersect, in particular forming an angle of 85° to 95°, in particular an angle of about 90°. The elongate elements 1A1 are substantially parallel to one another, and likewise the elongate elements 1A2 are substantially parallel to one another.

[0197] The elongated elements 1A2 are extruded and deposited layer on layer of the elongated elements 1A1, and are fixed to the elongated elements 1A1 via heat-sealed polymer parts 5 originating from the elongated elements 1A2 and / or the elongated elements 1A1, as shown in Figure 2. When depositing the elongated elements 1A2, the elongated elements 1A1 have previously been extruded and deposited in alignment on a support, in particular a non-stick support.

[0198] FIG. 3 schematically shows assembly 1B placed on assembly 1A shown in FIGS. 1 and 2. Assembly 1B is rotated relative to assembly 1A by an angle λ1, particularly 30° to 40°, for example, approximately 36°, formed between directions LA1 and LB1. FIG. 3 also schematically shows assembly 1C placed on top of assembly 1B. Assembly 1C is rotated relative to assembly 1B by an angle λ2, particularly 30° to 40°, for example, approximately 36°, formed between directions LB1 and LC1. Assemblies 1A, 1B, and 1C placed one on top of the other in this manner form a base layer 10 according to the present invention.

[0199] As shown in FIG. 3, the assemblies 1B are spaced apart by d 1B1 a layer of a plurality of extruded elongated elements 1B1 spaced apart and oriented in a longitudinal direction LB1, and a layer of a plurality of extruded elongated elements 1B1 spaced apart from each other by a distance d 1B2 and a layer of a plurality of extruded elongated elements 1B2 spaced apart and oriented in a longitudinal direction LB2, said direction LB1 and said direction LB2 intersecting and in particular forming an angle of 85° to 95°, in particular about 90°. The elongated elements 1B1 are substantially parallel to one another, and likewise the elongated elements 1B2 are also substantially parallel to one another.

[0200] Similarly, the assemblies 1C are spaced apart by d 1C1 and a layer of a plurality of elongated elements 1C1 arranged at intervals d 1C2 and a layer of a plurality of elongated elements 1C2 spaced apart and oriented in a longitudinal direction LC2, said direction LC1 and said direction LC2 intersecting and in particular forming an angle of 85° to 95°, in particular about 90°. The elongated elements 1C1 are substantially parallel to one another, and likewise the elongated elements 1C2 are also substantially parallel to one another.

[0201] Advantageously, the elongate elements (1A1, 1A2, 1B1, 1B2, 1C1, 1C2) are deposited according to the above arrangement so as to form the base layer immediately after extrusion and are bonded to one another via heat seals which act as adhesive connection points.

[0202] Preferably, an upper base layer (e.g., layer n+1) is disposed on a lower base layer (e.g., layer n) such that the elongated elements A1 and A2 of the upper layer are substantially parallel to the elongated elements A1 and A2 of the lower layer, respectively. Preferably, base layer n+1 is similar to base layer n, i.e., the configuration of the elongated elements and their stacking structure are similar.

[0203] FIG. 4 shows a second example of a base layer 20 according to the present invention, which is a variation of the first example of the base layer 10, the layered structure of which is shown in FIG. 3. The second example of the base layer 20 differs from the first example 10 in that the elongated elements (2A1, 2A2, 2B1, 2B2, 2C1, 2C2) have sinusoidal or zigzag loci with alternating peaks and valleys, such as the peaks 2A1a and valleys 2A1b shown in the elongated element 2A1. This arrangement improves the flexibility of the base layer 20. Advantageously, the elongated elements (e.g., 2A2, 2B2, 2C2) of an upper layer of a given assembly (e.g., 2A, 2B, 2C) are arranged above the elongated elements (e.g., 2A1, 2B1, 2C1) of a lower layer of the same assembly, with the valleys and peaks of the upper layer cooperating with the peaks and valleys of the lower layer, respectively. This arrangement improves the mutual fixation and retention of the elongate elements and improves the mechanical strength of the base structure (ie, the ability of the structure to withstand mechanical stresses before and after implantation).

[0204] FIG. 5 shows an isometric view of the unit base layer 20, with the three directions in space (X, Y, Z) shown with equal importance.

[0205] FIG. 6 shows a schematic front view of the unit base layer 20.

[0206] Figure 7 shows a side view of a base layer 20 having a thickness eb of about 1.2 mm. Figure 8 is a photograph of a first example of an implantable device 100 according to the present invention. The implantable device 100 includes a base structure 110 made up of multiple base layers stacked one on top of the other to achieve a desired final thickness.

[0207] 9 and 11 are also photographs obtained by tomography of the implantable device 100. When taking a tomographic photograph, radiation (X-rays) penetrates the implantable device 100, which is positioned between a beam source and a detector, along a beam. The distribution of matter within the object is represented by linear attenuation and spatial parameters. The resolution used to analyze the implantable device 100 is 33 microns.

[0208] In this particular example, the base structure 110 has a thickness of about 5 mm between the first and second opposing surfaces. The base structure 110 includes three base layers 20 that are stacked without rotation relative to one another. The elongated elements of the base structure 110 are extruded from a copolymer of ε-caprolactone and L-lactic acid, with a mass fraction based on ε-caprolactone repeat units of about 30% and a mass fraction based on lactic acid repeat units of about 70%. The porosity of the base structure 110 is about 94.5% and the density is about 0.04 g / cm. 3 is.

[0209] The base layer may be, for example, base layer 10 or 20. The final thickness of base structure 110 can be adjusted by adding an assembly A or by adding additional assemblies A and B.

[0210] As shown in FIGS. 8-11, the base structure has a number of open and interconnected pores (eg, pores 112 and 114) extending between its first and second opposing surfaces.

[0211] As shown in FIG. 10, the base structure 110 includes a portion of an elongated element having a diameter d120 or a width of about 0.20 mm, for example selected from elongated elements 1A1, 1A2, 2A1, 2A2, 1B1, 1B2, 2B1, 2B2, 1C1, 1C2, 2C1, or 2C2.

[0212] FIG. 11 shows the surface area (mm ) of the pores of the base structure 110, including in particular the laminated base layer 20. 2 ) distribution (%) is shown.

[0213] Figure 12 shows the pore size in mm because it is measured on a plane. 2 The surface area of ​​the pore is given by the formula 2 x π x radius. 2 The diameter (mm) can be calculated by:

[0214] It can be seen that in the base structure 110, pores of a size corresponding to "microfat," i.e., 1.25 mm or less, are most prevalent. Next, pores of a size corresponding to "millifat," i.e., 1.25 mm to 2.5 mm, constitute the second most prevalent category of pores, and finally, pores of 2.5 mm or more, which correspond to "macrofat," constitute the least prevalent category of pores.

[0215] 13 shows a histological section taken from the implantable device 100 two months after implantation, demonstrating good adipocyte density and quality as evidenced by heterogeneity in adipocyte size. The lack of intercellular spaces and the presence of little connective tissue indicate good maintenance of adipocyte volume.

[0216] Figure 14 shows angiogenesis in the implantable device 100 tested in Figure 11. The base structure 110 comprises portions of elongate elements 120 and pores that allow angiogenesis, resulting in the formation of small blood vessels, such as blood vessel 130, and large diameter blood vessels, such as blood vessel 140. Advantageously, the distribution and size of the pores can guide the direction of the blood vessels, resulting in uniform angiogenesis in the adipose tissue.

[0217] 15 compares, without limitation, the Young's modulus of implantable device 100, including base structure 110, with that of adipose tissue, showing that the Young's moduli are similar, averaging close to 10 KPa.

[0218] Implantable devices according to the present invention can achieve a similar Young's modulus even when the elongated elements are made of one or more polymers other than the copolymer of caprolactone and lactic acid selected for device 100.

[0219] Compression tests to measure Young's modulus were conducted in accordance with ASTM D1621-16, "Standard Test Method for Compressive Properties of Rigid Cellular Plastics." During testing, six standardized specimens, each 60.0 mm in diameter and 26.4 mm in height, were immersed in a stationary distilled water bath mounted on the lower plate of the testing machine. The temperature of the water bath was controlled at 37°C. The upper plate was lowered at a constant rate of 2.6 mm / min, compressing the specimens. The cell used was 250 N. Force and displacement were recorded and post-processed to obtain the compressive modulus.

Claims

1. A bioabsorbable implantable device (100), in particular for soft tissue replacement and / or reconstruction and / or augmentation, said implantable device (100) comprising a base structure (110), said base structure (110) comprising at least one base layer (10, 20), said base layer comprising: an assembly A (1A, 2A) comprising a layer of elongated elements A1 (1A1, 2A1) spaced apart from one another and oriented in a longitudinal direction LA1, and a layer of elongated elements A2 (1A2, 2A2) spaced apart from one another and oriented in a longitudinal direction LA2, wherein the direction LA1 and the direction LA2 intersect; an assembly B (1B, 2B) comprising a layer of elongated elements B1 (1B1, 2B1) spaced apart from one another and oriented in a longitudinal direction LB1, and a layer of elongated elements B2 (1B2, 2B2) spaced apart from one another and oriented in a longitudinal direction LB2, wherein the direction LB1 and the direction LB2 intersect; Including, the assembly B (1B, 2B) is at least partially disposed on the assembly A (1A, 2A); The direction LA1 intersects with the direction LB1, An implantable device (100) wherein the base structure (110) comprises a plurality of base layers (10, 20) arranged at least partially on top of one another.

2. 2. The implantable device of claim 1, wherein the base layer comprises an assembly C (1C, 2C) including a layer of elongated elements C1 (1C1, 2C1) spaced apart from one another and oriented in a longitudinal direction LC1, and a layer of elongated elements C2 (1C2, 2C2) spaced apart from one another and oriented in a longitudinal direction LC2, wherein the directions LC1 and LC2 intersect, and the assembly C (1C, 2C) is at least partially arranged on the assembly B (1B, 2B), in particular the direction LC1 intersects the direction LB1.

3. 3. The implantable device (100) of claim 1 or 2, wherein the direction LA1 intersects with the direction LB1 and forms an angle λ1 at the intersection that is greater than 10° and less than or equal to 60°.

4. 4. An implantable device (100) according to claim 2 or 3, characterized in that the direction LA1 intersects with the direction LC1 and at the intersection forms an angle λ3 that is at least 10° greater than λ1.

5. 5. An implantable device (100) according to any one of claims 1 to 4, characterized in that the angle formed between the direction LA1 and the direction LA2 is between 70° and 110°.

6. An implantable device (100) according to any one of claims 1 to 5, characterized in that the elongated element A1 (1A1) is fixed to a plurality of elongated elements A2 (1A2) by a solidified thermal melt (5) arising from the elongated element A1 and / or the elongated element A2.

7. An implantable device (100) according to any one of claims 1 to 6, characterized in that at least one elongate element A1 (2A1) has a zigzag or sinusoidal shape for at least a portion a11 of its length.

8. 8. The implantable device (100) of claim 7, wherein at least one elongate element A2 (2A2) has at least a portion a22 of its length in a zigzag or sinusoidal shape, said portion a22 including valleys spaced apart from one another, and said portion a11 of said elongate element A1 being arranged over said portion a22 of said elongate element A2 so as to pass through the valleys of said zigzag or sinusoidal portion a22.

9. The density of the base structure (110) is 0.01 g / cm ３ 1g / cm or more ３ An implantable device (100) according to any one of claims 1 to 8, characterized in that:

10. 10. An implantable device (100) according to any one of claims 1 to 9, characterized in that at least a portion of the elongated elements selected from the elongated elements A1 (1A1, 2A1), A2 (2A1, 1A2), B1 (1B1, 2B1) and B2 (1B2, 2B2), in particular C1 (1C1, 2C1) and C2 (1C2, 2C2), are sections of monofilament thread having a diameter or width of 0.60 mm or less, preferably 0.40 mm or less.

11. 11. The implantable device (100) according to any one of claims 1 to 10, characterized in that at least a portion of the elongate elements selected from the elongate elements A1, A2, B1 and B2, in particular C1 and C2, comprise at least one bioabsorbable copolymer comprising repeating units of ε-caprolactone and repeating units of L- or D- or L,D-lactide.

12. 12. The implantable device (100) of any one of claims 1 to 11, wherein the base structure (110) has a porosity of 90% or greater.

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

14. A method for manufacturing an implantable device (100) according to any one of claims 1 to 13, said method comprising: A step (i) of manufacturing a base layer (110), said step (i) comprising: a step (i1) of manufacturing an assembly A, comprising stacking a plurality of elongated elements A1 (1A1, 2A1) spaced apart from one another and oriented in a longitudinal direction LA1 to form a layer, and then stacking a plurality of elongated elements A2 (1A2, 2A2) spaced apart from one another and oriented in a longitudinal direction LA2 to form a layer disposed on top of the previous layer comprising said elongated elements A1 (1A1, 2A1), said direction LA1 and said direction LA2 intersecting; a step (i2) of manufacturing an assembly B (1B, 2B), comprising stacking a plurality of elongated elements B1 (1B1, 2B1) spaced apart from one another and oriented in a longitudinal direction LB1 to form a layer, and then stacking a plurality of elongated elements B2 (1B2, 2B2) spaced apart from one another and oriented in a longitudinal direction LB2 to form a layer disposed on top of the previous layer comprising said elongated elements B1 (1B1, 2B1), said direction LB1 and said direction LB2 intersecting; step (i) comprising: the assembly B (1B, 2B) is at least partially disposed on the assembly A (1A, 2A); The direction LA1 intersects with the direction LB1, The method of claim 1, wherein the implantable device (100) comprises a base structure (110) including a plurality of base layers (10, 20) disposed at least partially on top of one another.

15. 1. A method for extracorporeally manufacturing an implantable device (100) for replacing and / or reconstructing and / or augmenting a volume of soft tissue, the method comprising: Providing an implantable device (100) according to any one of claims 1 to 13, comprising a base structure (110) having a predetermined porous volume; and placing, at least partially within the porous volume of the base structure (110), cells selected from adipocytes, cells capable of differentiating into adipocytes, and a mixture of these two types of cells, said cells preferably originating from the subject; A method comprising:

Images