Implantable device for the progressive release of one or more functional agent(s) and method for manufacturing such a device

Abstract

The present invention relates to an implantable device, particularly for the reconstruction of an anterior cruciate ligament or tendon, comprising an elongated core (20) and an elongated hollow shell with an internal volume that at least partially houses said core. This elongated core is composed of a bioerodible polymer matrix in an aqueous medium and one or more functional agents, and the shell has through-holes in fluid communication with said internal volume. The invention also relates to a method for manufacturing said implantable device.

Description

Technical Field

[0001] The present invention relates to the technical field of implantable devices with progressive release of one or more functional agent(s), in particular of an osteo-inducing and / or osteo-conducting agent, especially for the reconstruction of an anterior cruciate ligament. Previous technique

[0002] Acute ligament injury, particularly rupture of the anterior cruciate ligament (ACL), especially in the knee, is common, especially among athletes. Studies estimate that this type of injury affects approximately 100,000 to 200,000 athletes in the USA each year. In addition to joint instability, clinical signs may include pain and post-traumatic swelling.

[0003] Anatomically, the anterior cruciate ligament (ACL) is a structure that connects the femur to the tibia, and ensures various movements in the anterior direction and inhibits extreme rotation of the knee.

[0004] Ligaments are known to be non-regenerative and to have limited vascularization. ACLs, therefore, have a poor capacity to heal on their own.

[0005] At least 150,000 ACL surgeries are performed annually in the USA to repair ACL abnormalities and restore normal function. Generally, ACL repair and function restoration strategies rely on autografts or allografts, such as Hamstring tendon autografts and patellar tendon autografts. The surgical technique involves inserting a graft into a tunnel drilled in bone and fixing it between the tibia and femur with specific fixation devices, such as interference screws. This type of procedure often requires subsequent revision surgery. In addition to the risks of comorbidities (infection, rejection, etc.), there are also significant risks associated with ACL reconstruction.) associated with the use of biological grafts, ACL reconstruction can fail due to certain problems, such as the intercondylar roof, graft impacts, placement in a non-anatomical tunnel or the inability to form a transition zone at the interface of the graft and the bone.

[0006] Incomplete ligament healing can compromise the success of a reconstruction procedure due to a lack of osseointegration. This lack of osseointegration affects approximately 15% to 25% of patients treated surgically.

[0007] The histological and biomechanical properties of the ACL are determined by the anthesis, the attachment site present in the native ACL, which is composed of three regions: fibrocartilaginous tissue, the ligament, and bone. The reproduction of these structures plays a crucial role in the success of ligament reconstruction, particularly of the ACL.

[0008] Devices for the reconstruction of ligaments or tendons are known from documents IT-A-2018 0000 2536 and EP-A-0 452 807.

[0009] There is thus a need for implantable interfacial tissue-engineered structures. Recently, tissue-engineered structures have received increasing interest and are considered a promising alternative for developing a therapeutic approach that addresses bone defects and restores living tissue using biomaterials, cells, and growth factors. Attempting to recreate bone morphology is one of the most complex research topics due to the complexity of this bone structure and its ability to constantly remodel and change its shape. Histologically, bone is made of living cells and an extracellular matrix secreted by osteoblasts. The matrix is ​​composed of two phases: the first phase comprises organic elements that consist primarily of type I collagen (90%) and non-collagenous proteins (10%).This first phase is responsible for bone flexibility and resistance to torsion and tension. The second phase is the mineralized phase, consisting of 60% of the volume of the extracellular matrix and containing hydroxyapatite (Ca10(PO4)6(OH)12) arranged in crystals, ensuring bone hardness.

[0010] The implantable device for bone tissue engineering must be biocompatible, possibly fully or partially biodegradable, promote osseointegration and be sufficiently mechanically resistant to withstand the tensile and / or rotational loads experienced by a tendon or ligament.

[0011] Furthermore, the structure of implantable devices in a hydrophobic synthetic material, for example polyethylene terephthalate, tends to inhibit tissue adhesion.

[0012] Therefore, there is a need for an implantable bone tissue engineering device that solves the aforementioned problems. Description of the invention

[0013] The present invention advantageously relates to an implantable device for bone tissue engineering, in particular in the reconstruction of a ligament or tendon in connection with a bone element having a structure that reproduces / imitates the bone extracellular matrix and promotes bone formation, i.e. promotes osteo-conduction.

[0014] The present invention advantageously relates to an implantable device promoting osseointegration, mechanically imitating the behavior of a ligament or tendon, and promoting cell adhesion.

[0015] The present invention relates to a device and a method as defined in the accompanying claims.

[0016] The present invention relates, according to a first aspect, to an implantable device that addresses all or part of the aforementioned problems, particularly for the reconstruction of an anterior cruciate ligament or tendon. The device comprises a longitudinal core and a hollow longitudinal covering member with an internal volume that receives at least part of said longitudinal core. Advantageously, said longitudinal core comprises a bio-erodible polymer matrix in aqueous media and one or more functional agent(s), and the covering member comprises through-holes in fluidic communication with said internal volume.

[0017] Advantageously, the bio-erodible polymer matrix is ​​arranged in the internal volume of the hollow limb, so that its progressive disintegration, in particular its progressive solubilization, is slowed down by the structure of the long, slender hollow limb.

[0018] Furthermore, the combination of the long core and the long hollow limb provides the mechanical resistance properties in tension and torsion required to reproduce the properties of a tendon or ligament.

[0019] Advantageously, the long, hollow limb also allows the functional agent(s) to be immobilized in the internal volume in a controlled manner according to the arrangement of the traversing orifices retained.

[0020] This particular provision of the device allows for the control of the progressive release of the functional agent(s).

[0021] The progressive release is thus controlled on the one hand by the bio-erodible nature in aqueous environment of the matrix but also by the mechanical barrier of the hollow limb whose structure is determined to allow on the one hand the release of the functional agent(s) through its orifices but also to allow the formation of bone according to its external surface.

[0022] The term "implantable device" in this text means any device configured to be implanted in a human or animal body for a period of several days to several months or several years. Bio-erodible polymer matrix

[0023] In this text, bio-erodible means the degradation, disassembly, or digestion of the polymer matrix, and in particular of the bio-resorbable polymer(s) that the matrix comprises, by the action of one or more environmental biological factor(s) (for example, the acidity, temperature, or humidity of the target site, the existence of enzyme(s), protein(s) or other molecule(s) on the target site) or by the action of the physical or chemical properties of the functional agent(s) dispersed in the matrix, preferably by the action of at least an aqueous medium, and even more preferably by the action of the water contained in the environment of the implantation site.

[0024] In this text, a polymer matrix is ​​understood to mean a physical structure of polymer(s) that retains one or more functional agent(s).

[0025] Advantageously, the polymer matrix comprises one or more bio-resorbable polymer(s), in particular having a determined solid structure before its contact with an aqueous medium.

[0026] Preferably, in this text the term "polymer" is understood to mean: a polymer or oligomer comprising one repeating motif or two or three or more repeating motifs different from each other.

[0027] In this text, the term copolymer refers to any polymer or oligomer comprising two or more different repeating motifs.

[0028] In particular, in this text, an oligomer comprises a number of repeating motifs less than or equal to 10, and a polymer comprises a number of repeating motifs greater than 10.

[0029] In this text, bio-resorbable (or resorbable) means any material which, when placed in a living organism, will disappear after a specified period, for example after three days, or after 3 months, 6 months, or more.

[0030] A person skilled in the art knows which bio-resorbable material to choose, in particular according to its degree of polymerization and / or its degree of cross-linking and / or its chemical nature, to obtain resorption at the end of a determined period.

[0031] Advantageously, the implantable device is an artificial ligament or an artificial tendon, in particular osteo-conductive and / or osteo-inductive.

[0032] Advantageously, the polymer matrix is ​​water-soluble, that is to say, in contact with water, in particular in contact with a physiological environment, said matrix dissolves progressively, for example said matrix is ​​totally dissolved after 3 months or 6 months or more depending on the needs.

[0033] In particular, the polymer matrix is ​​water-soluble upon contact with the aqueous environment of the area of ​​the living organism in which it is implanted.

[0034] In particular, the polymer matrix is ​​water-soluble in contact with a medium containing water and having a temperature greater than or equal to 20°C, in particular greater than or equal to 25°C, 30°C, 35°C or 37°C. Preferably, the aqueous medium comprises at least 50%, 60%, 70%, 80% or 90% by mass or volume of water, in particular distilled and / or reverse osmosis water.

[0035] The aqueous medium can be a physiological medium, in particular an aqueous medium comprising distilled water, and sodium chloride (for example diluted at a rate of 0.9% by mass of NaCl relative to the volume of the medium), and possibly other minerals such as potassium chloride, calcium chloride, magnesium sulfate or a mixture of these.

[0036] Advantageously, one or more functional agent(s), in particular the functional agent(s), is / are dispersed in the bio-erodible polymer matrix.

[0037] Preferably, the bio-erodible polymer matrix comprises the functional agent(s). Preferably, the mass of the bio-erodible polymer matrix and one or more functional agent(s) is greater than or equal to 0.05 g / meter of implantable device and less than or equal to 10 g / meter of implantable device, more preferably less than or equal to 5 g / meter or 3 g / meter or 2 g / meter or 1 g / meter.

[0038] Preferably, the implantable device has an overall elongated structure and a determined length (cm). Functional agent(s)

[0039] Advantageously, in this text, a functional agent is understood to mean any agent having a function of bone integration, in particular osteo-conductive and / or osteo-inductive, and / or any agent having a prophylactic function and / or a curative function of a given pathology.

[0040] In this text, the term osteo-inducing functional agent means any agent that induces the differentiation of stem cells into bone cells, particularly without an immune response.

[0041] In this text, the term osteoconductive functional agent means any functional agent that promotes bone formation. Slender soul

[0042] In the present text, a long-spanning core is advantageously understood to mean any element having a length significantly greater than its thickness or width, for example, a length greater than at least 5 or 8 or 10 or 15 or 20 or 30 times the width or thickness of said long-spanning core.

[0043] The long, thin core is preferably a long, thin textile core.

[0044] The long core may include (or can be) one or more twisted, wrapped or braided yarn(s), for example it is a braid, in particular a solid one; a narrow knitted or narrow woven strip, for example it may be a knitted tube; or a strip in one or more non-wovens, in particular heat-sealed.

[0045] Preferably, the long, thin textile core comprises one or more threads and / or fibers.

[0046] Preferably, the elongated core is non-absorbable.

[0047] In this text, non-absorbable means any material or structure which, when implanted in a living organism, will not be absorbed, that is to say, will remain for several years without significant degradation of its structure.

[0048] The long, textile core is preferably a braid, especially a solid one (i.e., not hollow).

[0049] The long, thin core preferably has a diameter less than or equal to 20 mm or 15 mm or 10 mm or 8 mm or 5 mm.

[0050] The elongated core preferably has a diameter greater than or equal to 1 mm, 2 mm, or 3 mm. The elongated core preferably has a length greater than or equal to 10 mm, 20 mm, 30 mm, 40 mm, 50 mm, or 80 mm.

[0051] The long core preferably has a length less than or equal to 150 mm or 130 mm or 110 mm or 90 mm or 70 mm or 50 mm or 40 mm or 30 mm.

[0052] Advantageously, the long-slender core has an outer surface oriented directly opposite the inner surface of the hollow long-slender member.

[0053] Advantageously, the elongated core has a linear density greater than 0 g / linear meter and less than or equal to 10 g / linear meter, or 8 g / linear meter, or 5 g / linear meter, or 4 g / linear meter, or 3 g / linear meter, or 2 g / linear meter, or 1 g / linear meter, for example, is between 0.50 g / linear meter and 0.80 g / linear meter. Advantageously, the elongated core has a porous surface, that is, comprising openings, possibly through-holes. The pores are advantageously formed by the interstices between the yarn(s) and / or fibers.

[0054] In one embodiment, the longitudinal core comprises between 8 and 20 textile strands, in particular braided, each textile strand comprising one or more yarn(s). In another embodiment, the longitudinal core (in particular the auxiliary textile cover) comprises between 12 and 18 textile strands (for example, on the order of 16 textile strands), in particular braided, each textile strand comprising one or more yarn(s).

[0055] Preferably, the longline textile core comprises several multifilament yarns, again preferably each having a count greater than or equal to 50 dtex and less than or equal to 500 dtex or 350 dtex or 300 dtex.

[0056] Preferably, the longline textile core, especially braided, comprises a first multifilamentary yarn having a T1 (dtex) count, and a second multifilamentary yarn having a T2 (dtex) count, the T2 / T1 ratio being greater than or equal to 1.5; especially greater than or equal to 2.

[0057] Preferably, the long, slender textile core comprises: An auxiliary core comprising one or more yarns (in particular two or three yarns), particularly multifilament yarns, more particularly having at least one of said yarns (in particular all three) with a dtex count ranging from 100 dtex or 150 dtex to 300 dtex or 250 dtex; and an auxiliary textile cover, particularly braided, around said auxiliary core, particularly comprising one or more multifilament yarns, more particularly comprising said first and second multifilament yarns described in the preceding paragraph. Advantageously, the auxiliary core comprises one or more untwisted multifilament yarns or yarns arranged substantially parallel to each other. Long, hollow cover member

[0058] In this text, a long-walled hollow cover member is advantageously understood to mean a cover member having a length significantly greater than its thickness or width, for example, a length greater than at least 5 or 8 or 10 or 15 or 20 or 30 times the width or thickness of said cover member.

[0059] The long, hollow limb is preferably a long, hollow textile limb.

[0060] Preferably, the long hollow cover member and the long core are arranged coaxially, in particular their respective central longitudinal axes are substantially coincident.

[0061] In general, the term textile in this text means any element (core, hollow member, etc.) obtained by manipulating one or more thread(s) and / or fiber(s).

[0062] Preferably, the hollow longitudinal cover member is a textile longitudinal member, and may comprise (or may be) a knitted tube; a hollow braid; or a tube in one or more nonwovens, including heat-sealed ones.

[0063] Preferably, the long, hollow textile limb comprises one or more threads and / or fibers. Preferably, the long, hollow limb is non-absorbable.

[0064] The long, slender textile member is preferably a hollow braid.

[0065] The long, hollow limb preferably has an outside diameter less than or equal to 20 mm or 15 mm or 10 mm or 8 mm or 5 mm.

[0066] The long, hollow limb preferably has an outside diameter greater than or equal to 1 mm or 2 mm or 3 mm.

[0067] The long, hollow limb preferably has a length greater than or equal to 10 mm or 20 mm or 30 mm or 40 mm or 50 mm or 80 mm.

[0068] The hollow longitudinal member preferably has a length less than or equal to 150 mm, 130 mm, 110 mm, 90 mm, 70 mm, 50 mm, 40 mm, or 30 mm. Advantageously, the hollow longitudinal cover member has an inner surface oriented directly opposite the outer surface of the longitudinal web. Advantageously, the hollow longitudinal cover member has an outer surface substantially opposite its inner surface.

[0069] Preferably, the wall thickness of the hollow slender limb extends between its inner and outer surfaces.

[0070] Advantageously, the long hollow cover member has a linear mass greater than 0 g / m²< and less than or equal to 10 g / linear meter or 8 g / linear meter or 5 g / linear meter or 4 g / linear meter or 3 g / linear meter or 2 g / linear meter or 1 g / linear meter, for example is between 0.50 g / linear meter and 0.90 g / linear meter.

[0071] Advantageously, the hollow longitudinal cover member includes through openings, in particular extending between its inner surface and its outer surface, notably opening onto said inner and outer surfaces of the hollow longitudinal cover member.

[0072] The pores are advantageously formed by the spaces between the thread(s) and / or fibers. These openings allow fluidic communication between the internal volume of the elongated limb and its external surface. Thus, the functional agent(s) contained within the bio-erodible polymer matrix are released as it degrades, first within the internal volume and then across the external surface of the elongated limb. The external surface of the elongated limb thus advantageously forms an external surface for osseointegration.

[0073] Preferably, the long, hollow limb is over-knitted or over-braided, preferably over-braided, around the long, slender core.

[0074] In one embodiment, the long member comprises between 8 and 20 textile strands, in particular braided, each textile strand comprising one or more threads. In another embodiment, the long member comprises between 10 and 18 braided textile strands (in particular 12 or 16 braided strands), each textile strand comprising one or more threads, more particularly between 3 and 8 threads.

[0075] Preferably, the long hollow member, especially braided, comprises several multifilamentary yarns (especially braided), more preferably between 30 and 75 or 70 multifilamentary yarns, preferably between 40 and 70 multifilamentary yarn(s), especially between 50 and 70 multifilamentary yarns or between 55 and 70 multifilamentary yarns or between 60 and 68 multifilamentary yarns, each yarn having a count greater than or equal to 50 dtex or 80 dtex or 100 dtex and less than or equal to 300 dtex or 250 dtex or 200 dtex or 150 dtex. Through holes

[0076] The through-holes can have any shape; they can be ovoid or polygonal, in particular.

[0077] When the orifices are ovoid, the orifices are preferably circumscribed within a circle with a diameter of 20 µm to 5000 µm, or even more preferably with a diameter of 20 µm to 500 µm. When the orifices are polygons, the side lengths of the polygons are preferably greater than or equal to 20 µm and less than or equal to 5000 µm, or even more preferably greater than or equal to 20 µm and less than or equal to 500 µm. Wire(s) / Fiber(s)

[0078] The yarn(s) (in particular of the longline core and / or the cover member and / or the auxiliary longline core and / or the auxiliary cover member) may be a monofilamentary yarn, a spun fiber yarn, or a multifilamentary yarn.

[0079] The yarn(s) and / or fiber(s) may comprise a material (or be in a material) selected from: polyesters, in particular polyethylene terephthalate (PET), for example Dacron®, and polybutylene terephthalate (PBT); polyamides, such as PA 6-6, PA 6, PA 4-6; polyolefins, such as polypropylene, polyethylene (in particular low-density or high- or very-high-density); lactic acid polymers and possibly glycolic acid polymers, such as PLLA, PLDA, and PLGA.

[0080] The thread(s) and / or fiber(s) may be bioresorbable, non-bioresorbable, or semi-bioresorbable, preferably non-bioresorbable.

[0081] Advantageously, a multifilamentary thread comprises a number of filaments between 5 and 30, in particular between 5 and 20 filaments.

[0082] Advantageously, a filament of a multifilament yarn has a linear mass between 1 dtex and 30 dtex, preferably between 5 dtex and 20 dtex.

[0083] Preferably, the yarn(s) comprises at least one material selected from: polyester(s); in particular polyethylene terephthalate (PET), for example Dacron ®< , or polybutylene terephthalate (PBT); or polyolefins, such as polypropylene, polyethylene (in particular low density or high or very high density); or a mixture of these.

[0084] Preferably, the yarn(s) are made of polyethylene terephthalate (PET), for example Dacron®, or of polybutylene terephthalate (PBT); or of polypropylene or polyethylene; or even a mixture of the latter (for example one or more yarns is / are made of PET or PBT and one or more yarns is / are made of PP or PE).

[0085] Advantageously, the bio-erodible polymer matrix forms a polymer coating covering at least part of the outer surface of the elongated core, in particular the outer surface of the textile auxiliary cover.

[0086] Advantageously, the bio-erodible polymer matrix fully permeates the slender core.

[0087] In particular, it is understood by impregnate at heart that the long core comprises polymer matrix coating at least in part the textile auxiliary core and the textile auxiliary cover.

[0088] In one variant, the longline textile core, in particular comprising an auxiliary textile core and an auxiliary textile cover arranged at least partly around said auxiliary textile core, and the hollow textile cover member form a textile assembly having a total count greater than or equal to 18,000 dtex and less than or equal to 25,000 dtex, preferably less than or equal to 24,000 dtex, more preferably less than or equal to 22,000 dtex, in particular greater than or equal to 20,000 dtex, more particularly greater than or equal to 21,000 dtex.

[0089] In one variant, the functional agent(s) includes one or more osteo-inducing and / or osteo-conducting agent(s).

[0090] In one variant, the osteo-inducing and / or osteo-conducting agent(s) is / are selected from: bioglasses; calcium phosphate-based bioceramics, in particular hydroxyapatites and tricalcium phosphate, and a mixture thereof. Advantageously, the osteo-inducing and / or osteo-conducting agent(s), or the osteo-inducing and / or osteo-conducting agent(s), comprises one or more osteo-inducing and / or osteo-conducting agents, which is / are selected from bioglasses.

[0091] Advantageously, the osteo-inducing and / or osteo-conducting agent(s), or the osteo-inducing and / or osteo-conducting agent(s), comprises one or more osteo-inducing and / or osteo-conducting agents, which is / are selected from calcium phosphate-based bioceramics, in particular hydroxyapatites, and tricalcium phosphate, or a mixture thereof.

[0092] Preferably, hydroxyapatite is a calcium phosphate that belongs to the apatite family; it is a generic name designating phosphates of variable composition.

[0093] Preferably, the bioglass is 45S5 bioglass. Advantageously, this bioglass is osteoconductive and osteoinductive.

[0094] Preferably, bioglasses are bioceramics comprising silica, sodium, calcium and phosphate, in particular in varying quantities, more specifically the mass fraction of silica (especially SiO2) is predominant compared to the other components.

[0095] The osteo-inducing and / or osteo-conducting agent(s) is / are water-soluble or non-water-soluble, preferably water-soluble.

[0096] Preferably, the osteo-inducing and / or osteo-conducting agent(s) is / are porous.

[0097] Preferably, the bioglass includes: of 30% by mass to 55% by mass of SiO2, in particular of 40% by mass to 50% by mass of SiO2; and / or of 15% by mass to 35% by mass of Na2O, in particular of 20% by mass to 30% by mass of Na2O; and / or of 15% by mass to 35% by mass of CaO, in particular of 20% by mass to 30% by mass of CaO; and / or of 2% by mass to 15% by mass of P2O5, in particular of 4% by mass to 10% by mass of P2O5.

[0098] In one variant, the functional agent(s) is / are chosen from: anti-inflammatories, antibiotics, antibacterials, analgesics, and a mixture of the latter.

[0099] In one variant, the bio-erodible polymer matrix comprises one or more functional agent(s) which is / are osteoinducing and / or osteoconducting agent(s), and optionally one or more other functional agent(s) selected from: anti-inflammatories, antibiotics, antibacterials, analgesics, and a mixture thereof.

[0100] In one variant, the long core includes a long textile core, in particular a braid.

[0101] In one variant, the long, textile core is coated at least in part with the bio-erodible polymer matrix in which the functional agent(s) is / are dispersed.

[0102] The coating in the bio-erodible polymer matrix can be continuous, for example in the form of a film, or discontinuous, for example arranged in the form of dots, strips, various patterns or a combination thereof.

[0103] Advantageously, the long core is coated on its outer surface with the bio-erodible matrix comprising one or more functional agent(s), totally or in part.

[0104] In one variant, the long hollow cover member includes a long textile cover member, in particular includes a hollow braid.

[0105] Advantageously, the cover member is over-braided around the long core so that the whole is perfectly homogeneous and has good cohesion.

[0106] In one variant, the bio-erodible polymer matrix comprises one or more mixed polymers, dehydrated and capable of forming a soluble gel in an aqueous medium. Advantageously, said dehydrated polymer(s) is / are one or more bio-erodible polymer(s), in particular bio-resorbable.

[0107] Advantageously, the polymer matrix is ​​solid at room temperature, i.e. at a temperature greater than or equal to 0°C and less than or equal to 40°C or 37°C or 30°C, the polymer matrix comprising at most 10% or 5% by mass of water relative to its total mass (including the functional agent(s)).

[0108] When the polymer matrix is ​​in contact with an aqueous medium, the matrix absorbs the water, may possibly swell depending on the polymer used, then gradually dissolves, releasing the dispersed functional agent(s) it contains.

[0109] In this text, a dehydrated polymer is defined as any polymer capable of forming a gel in an aqueous environment and then gradually dissolving. The polymer is not in gel form before implantation; therefore, it is dehydrated.

[0110] In one variant, the bio-erodible polymer matrix comprises one or more bio-resorbable polymer(s) selected from the following polymers: (co)polymers of cyclodextrin(s) and / or cyclodextrin derivative(s) and / or soluble cyclodextrin inclusion complex(s) and / or cyclodextrin derivative(s); a cross-linked or non-cross-linked polysaccharide derivative such as collagen polymers; hyaluronic acid-derived polymers; carboxymethylcellulose polymers or carboxymethylcellulose derivatives; vinyl polymers such as polyvinylpyrrolidone (PVP) or polyvinylpolypyrrolidone (crospovidone) polymers; polyethylene glycol polymers; lactic acid polymers; lactic acid-polyethylene glycol (PLLA / PEG) copolymers; lactic acid, glycolic acid and polyethylene glycol (PLGA / PEG) copolymers; polyvinyl alcohol (PVA) polymers;and polyacrylate polymers such as polyhydroxyethyl methacrylate (PHEM); and a mixture of the latter.

[0111] In one embodiment, the bio-erodible polymer matrix comprises one or more bio-resorbable polymer(s) selected from vinyl polymers such as polyvinylpyrrolidone (PVP) polymers or polyvinylpolypyrrolidone (crospovidone) polymers, or a mixture thereof.

[0112] In one embodiment, the bio-erodible polymer matrix comprises one or more bio-resorbable polymer(s) selected from: (co)polymers of cyclodextrin(s) and / or cyclodextrin(s) derivative(s) and / or soluble cyclodextrin(s) inclusion complex(s) and / or cyclodextrin(s) derivative(s), or a mixture of the latter.

[0113] In one embodiment, the bio-erodible polymer matrix comprises one or more bio-resorbable polymer(s) selected from: a cross-linked or non-cross-linked polysaccharide derivative such as collagen polymers; or hyaluronic acid-derived polymers; or carboxymethylcellulose polymers or carboxymethylcellulose derivatives; or a mixture of the latter.

[0114] The bio-resorbable polymer(s) of the bio-erodible polymer matrix is / are preferably hydrolosuble(s).

[0115] Cyclodextrin (co)polymers and / or cyclodextrin derivative(s) and / or cyclodextrin inclusion complex(s) are preferably water-soluble.

[0116] These (co)polymers can be obtained by 1 / preparing in solid state a mixture of cyclodextrin(s) and / or cyclodextrin(s) derivative(s) and / or cyclodextrin(s) inclusion complex(s) and / or cyclodextrin(s) derivative(s), and a poly(carboxylic) acid or a poly(carboxylic) acid anhydride or a mixture of poly(carboxylic) acids and / or poly(carboxylic) acid anhydrides and, optionally, a catalyst; then by 2 / heating said solid mixture, at a temperature between 100°C and 200°C, for a period between 1 min and 60 min, preferably equal to 30 min.

[0117] Preferably, to prepare the mixture in solid form, an aqueous solution of cyclodextrin(s) and / or cyclodextrin derivative(s) and / or cyclodextrin inclusion complex(s) and / or cyclodextrin derivative(s) and a poly(carboxylic) acid and / or a polycarboxylic acid anhydride and / or a mixture of poly(carboxylic) acids and / or poly(carboxylic) acid anhydrides and, optionally, a catalyst is prepared, and the water from said solution is evaporated at a temperature between 40°C and 100°C, preferably under vacuum at 90°C.

[0118] Preferably, the catalyst is chosen from dihydrogen phosphates, hydrogen phosphates, phosphates, hypophosphites, alkali metal phosphites, alkali metal salts of polyphosphoric acids, carbonates, bicarbonates, acetates, borates, alkali metal hydroxides, aliphatic amines and ammonia, and preferably from sodium hydrogen phosphate, sodium dihydrogen phosphate and sodium hypophosphite.

[0119] Preferably, cyclodextrin is selected from α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin and cyclodextrin derivatives are selected from methylated or acetylated hydroxypropyl derivatives of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin and inclusion complexes of said cyclodextrins and said cyclodextrin derivative(s).

[0120] Preferably, the poly(carboxylic) acid and the polycarboxylic acid anhydride are selected from the following polycarboxylic acids and poly(carboxylic) acid anhydrides: saturated and unsaturated acyclic poly(carboxylic) acids, saturated and unsaturated cyclic poly(carboxylic) acids, aromatic poly(carboxylic) acids, and hydroxypoly(carboxylic) acids, preferably citric acid, poly(acrylic) acid, poly(methacrylic) acid, 1,2,3,4-butane tetracarboxylic acid, maleic acid, citraconic acid, itaconic acid, 1,2,3-propane tricarboxylic acid, aconitic acid, all-cis-1,2,3,4-cyclopentane tetracarboxylic acid, mellitic acid, and other similar acids. oxydisuccinic acid, thiodisuccinic acid.

[0121] Preferably, the poly(carboxylic) acid is chosen from among saturated or unsaturated acyclic poly(carboxylic) acids, saturated and unsaturated cyclic poly(carboxylic) acids, aromatic poly(carboxylic) acids, hydroxypoly(carboxylic) acids, preferably from citric acid, poly(acrylic) acid, poly(methacrylic) acid, 1,2,3,4-butanetetracarboxylic acid, 1,2,3-propane tricarboxylic acid, aconitic acid, all-cis-1,2,3,4-cyclopentanetetracarboxylic acid, mellitic acid, oxydisuccinic acid, thiodisuccinic acid.

[0122] In one variant, the bio-erodible polymer matrix comprises one or more polymer(s) selected from: polyvinylpyrrolidone (PVP) polymers; polyvinyl alcohol polymers; (co)polymers of cyclodextrin(s) and / or cyclodextrin(s) derivative(s) and / or cyclodextrin inclusion complex(s), in particular water-soluble, or a mixture thereof.

[0123] In one variant, the bio-erodible polymer matrix comprises one or more bio-erodible polymer(s), and the mass ratio (functional agent(s) / bio-erodible polymer(s)) in the polymer matrix, in particular the mass ratio (osteo-inducing agent(s) and / or osteo-inducer(s) / bio-erodible polymer(s)) in the polymer matrix, is greater than or equal to 0.20 and less than or equal to 1.8; preferably greater than or equal to 0.20 and less than or equal to 1; more preferably greater than or equal to 0.40 and less than or equal to 0.80; preferably greater than or equal to 0.50 and less than or equal to 0.70.

[0124] In one variant, the long hollow cover member comprises a braid comprising from 8, in particular from 12, to 30 braided strands, and each braided strand comprises from 2 to 8 yarns, preferably said yarns each having a count ranging from 80 dtex to 200 dtex.

[0125] Preferably, each braided strand comprises 3 to 8 strands, in particular 3 to 7 strands, more particularly 3 to 6 strands, possibly 5 to 7 strands, for example 4 strands.

[0126] Preferably, the cover member comprises 20 to 28 braided strands.

[0127] Preferably, the cover member comprises 8 to 18 braided strands, especially 10 to 18 braided strands, more particularly 12 to 16 braided strands, for example 12 braided strands or 16 braided strands.

[0128] This particular structure allows for through-holes whose dimensions are optimized for the progressive migration of the functional agent(s) according to the external surface of the covering limb, and in particular the formation of an external osseointegration surface when there is one or more osteo-inducing and / or osteo-conducting agent(s).

[0129] In one variant, the long hollow cover member comprises between 30 and 120 threads, preferably between 30 and 80 threads, in particular said threads are not bioresorbable.

[0130] Preferably, the long, hollow braided cover member comprises from 40 braided strands to 75 braided strands, more preferably from 45 braided strands to 68 braided strands, for example from 60 braided strands to 68 braided strands.

[0131] Preferably, at least one of said wires is a multifilamentary wire, in particular said wires are multifilamentary wires.

[0132] The cover member offers good mechanical performance while providing deformability due to the large number of multi-filament threads.

[0133] In one variant, the mass fraction of the bio-erodible polymer matrix comprising the functional agent(s) in said implantable device is greater than or equal to 5% and less than or equal to 25%, preferably greater than or equal to 10% and less than or equal to 20%.

[0134] Advantageously, the mass fraction of the bio-erodible polymer matrix and functional agent(s) is measured relative to the total mass of the implantable device, in particular including the polymer matrix, the functional agent(s), the long core and the hollow long cover member.

[0135] In one variant, the mass fraction of the elongated core (in particular of the bare elongated core), free of the polymer matrix and functional agent(s), and of the hollow elongated cover member (in particular of the bare hollow elongated cover member) measured against the total mass of the implantable device is greater than or equal to 50% or 60% or 70%, preferably greater than or equal to 75%.

[0136] The present invention relates, according to a second aspect, to a method for manufacturing an implantable device, in particular according to any one of the embodiments referred to in the first aspect of the invention, advantageously comprising: a) a step of applying a bio-erodible polymeric coating comprising one or more functional agent(s) on a slender core, in particular textile; b) a step of arranging, in particular overbraiding, a hollow slender cover member, in particular textile, around at least part of said slender core, in particular textile, coated at least in part; c) a step of recovering an implantable device comprising a slender core and a hollow slender cover member comprising an internal volume receiving at least part of said slender core, said slender core comprising a bio-erodible polymer matrix in aqueous medium, and one or more functional agent(s), and the cover member comprising through ports in fluidic communication with said internal volume.

[0137] In one embodiment, the application step a) includes an application step (a1) of a liquid preparation comprising one or more bio-erodible (co)polymer(s), or one or more precursor monomer(s) and / or oligomer(s) of said bio-erodible (co)polymer(s), in an aqueous medium, and further comprising one or more functional agent(s), on a long, thin core, in particular a textile core, and a drying step (a2), possibly followed by a polymerization step (a3).

[0138] The application step (a) may include an impregnation step (a1), a spraying step (a1), or a dipping step (a1), using a solution / dispersion comprising the (co)polymer(s) and / or the monomer(s) and / or the precursor oligomer(s) of said polymer(s), and optionally an expression step (a11), for example, a calendering step (a11). Step (a1) and / or step (a11) may be carried out several times, for example, at least 4 times or at least 8 times, depending on the desired carryover rate.

[0139] The liquid preparation can be an aqueous solution / dispersion, or a solvent-based solution / dispersion (other than water), or a solution / dispersion based on at least one alcohol, for example based on ethanol.

[0140] Preferably, the mass fraction of bio-erodible (co)polymer(s), or of precursor monomer(s) or oligomer(s) of said bio-erodible (co)polymer(s), in the liquid preparation (mass / volume) is greater than or equal to 5% and less than or equal to 30%, in particular greater than or equal to 10% and less than or equal to 25%.

[0141] The drying step (a2) preferably includes heating the long core coated at least partially with the liquid preparation so as to evaporate the water and / or one or more solvent(s), for example the heating temperature is between 70°C and 100°C or 90°C or 80°C, for 30 minutes or more until a solid bio-erodible polymer matrix is ​​formed.

[0142] The partially coated elongated core can then be heated in a polymerization step (a3) ​​during which the partially coated elongated core is heated so as to polymerize, possibly crosslink, the precursor monomer(s) or oligomer(s) of said bio-erodible (co)polymer(s), for example at a temperature of 150°C for at least 30 minutes in the case of cyclodextrin (co)polymers.

[0143] In one variant, step b) is a step of braiding a hollow braid on a braiding device (for example, a braiding machine) comprising a total number of spindles greater than or equal to 12, more particularly greater than or equal to 18, and less than or equal to 30, in particular less than or equal to 26, and the number of empty spindles is greater than or equal to 10% and less than or equal to 60% of the total number of spindles, in particular greater than or equal to 20% and less than or equal to 60% of the total number of spindles, in particular the number of full spindles is greater than or equal to 40% and less than or equal to 90% of the total number of spindles of the braiding device.

[0144] Advantageously, the number of full spindles is greater than or equal to 40%, in particular greater than or equal to 45%, and less than or equal to 90%, in particular less than or equal to 80%, more particularly less than or equal to 70%, of the total number of spindles in the braiding loom.

[0145] In one embodiment, the number of spindles of the braiding loom in step b) of overbraiding the cover member is between 20 and 26, in particular in the order of 24 spindles.

[0146] In one embodiment, the number of full spindles is between 60% and 75% of the total number of spindles on the braiding loom during step b).

[0147] In one embodiment, the number of solid spindles is between 10 and 18, in particular between 12 and 18, more particularly between 14 and 18.

[0148] In this text, a full spindle of a braiding loom is understood to mean that this spindle supports one or more thread(s) during braiding, and an empty spindle of a braiding loom is understood to mean that this spindle does not support any thread during braiding.

[0149] This arrangement of solid and empty spindles on the braiding loom allows the braided strands to be separated, and to form through holes which promote the gradual migration and fixation of functional agent(s) on the outer surface of the hollow, long-spanning covering member.

[0150] Preferably, the number of zones (full and / or empty) is an integer.

[0151] In one variant, step b) is a step of braiding a hollow braid on a braiding device comprising solid and empty spindles, and the solid spindles are distributed into at least three groups of solid spindles (in particular into four groups of solid spindles), each group comprising several neighboring solid spindles (in particular two or three or four neighboring solid spindles), and one group of solid spindles is separated from another group of solid spindles by at least one empty spindle, preferably by at least two or three empty spindles.

[0152] Advantageously, a group of solid spindles includes at least three or four neighboring solid spindles.

[0153] Preferably, the braiding device comprises 10 to 30 spindles, even more preferably 14 to 28 spindles, especially 20 to 28 spindles, notably 22 to 26 spindles.

[0154] In one embodiment, the braiding device comprises 4 groups of three or four adjacent or neighboring solid spindles, and 4 groups of 3 or 4 adjacent or neighboring empty spindles, with one group of adjacent or neighboring solid spindles being arranged between two groups of empty spindles.

[0155] In one variant, the braiding device comprises three or four groups of three or four adjacent solid spindles and three or four groups of adjacent empty spindles, with one group of adjacent solid spindles being arranged between two groups of adjacent empty spindles.

[0156] In one variant, step b) is a step of braiding a hollow braid with a substantially constant braiding angle greater than or equal to 2 mm and less than or equal to 15 mm, preferably greater than or equal to 4 mm and less than or equal to 10 mm.

[0157] Advantageously, the braiding angle can be measured under a microscope.

[0158] The present invention also relates, according to a third aspect, to an implantable device that can be obtained by the manufacturing process according to a second aspect of the invention.

[0159] In particular, the variants / embodyments / definitions according to a first aspect of the invention apply independently of each other to the implantable device according to a third aspect and to the manufacturing process according to a second aspect of the invention. Description of the drawings

[0160] The present invention will be better understood upon reading the following embodiments, cited by way of non-limiting example, and illustrated by the figures in which: [ Fig.1 ] there figure 1 schematically represents a first example of the arrangement of solid spindles with empty spindles of a braiding loom comprising 16 spindles in total for braiding a first example of a hollow, elongated roof member according to the invention; Fig. 2 ] there figure 2 schematically represents a second example of the arrangement of solid spindles with empty spindles of a braiding loom comprising 16 spindles in total for braiding a second example of a hollow, elongated roof member according to the invention; Fig.3 ] there figure 3schematically represents a third example of the arrangement of solid spindles with empty spindles of a braiding loom comprising 24 spindles in total for braiding a third example of a hollow, elongated cover member according to the invention; Fig. 4 ] there figure 4 schematically represents a fourth example of the arrangement of solid spindles with empty spindles of a braiding loom comprising 24 spindles in total for braiding a fourth example of a hollow, elongated cover member according to the invention; Fig. 5 ] there figure 5 is a photograph obtained by scanning electron microscopy of the outer surface of a first example of a long, thin core according to the invention, coated at least partially with a bio-erodible matrix comprising at least one osteo-inducing and / or osteo-conducting functional agent after 7 days of immersion in a simulated body fluid to study bio-mineralization; Fig. 6 ] there figure 6 is a photograph obtained by scanning electron microscopy of the outer surface of the third example of a cover member according to the invention after 7 days of immersion in a simulated body fluid to study bio-mineralization; [ Fig. 7 ] there figure 7 is a graph representing the mass proportion of calcium (Ca) and phosphorus (P) on the ordinate, measured by energy-dispersive X-ray spectroscopy on the outer surface of an example of a slender core according to the invention, referenced (IB) on the abscissa, on the inner surface of the third example of a cover member according to the invention, referenced (IF) on the abscissa, and on the outer surface of the third example of a cover according to the invention, referenced (EF), after 7 days of immersion in a simulated body fluid to study bio-mineralization; Fig. 8 ] there figure 8is a photograph obtained by scanning electron microscopy of the outer surface of the fourth example of a cover member according to the invention after 7 days of immersion in a simulated body fluid to study bio-mineralization. Description of the implementation methods A- Preparation of a polymer solution

[0161] Approximately 4.82g of poly(vinylpyrrolidone) (PVP) (of the brand Kollidone ®< medical grade, available in powder form, marketed by BASF, with Mw of 900,000 to 1,200,000 g / mol) is dissolved in 60 ml of 96% concentrated ethanol (in osmosis water, i.e. 96% w / v) at room temperature gradually to avoid precipitation of the polymer, the mixture is stirred gently at 150 rpm for at least 30 minutes.

[0162] Then, approximately 3g of 45S5 bioglass are added to the solution containing the PVP and dispersed within it. The bioglass concentration here is 10% by mass / volume of the solution.

[0163] The solutions are left to stir for 8 hours. B- Impregnation of a long, slender textile core

[0164] Advantageously, the longline textile core comprises an auxiliary core consisting of three multifilament polyester yarns (in particular polyethylene terephthalate), each of 190 dtex, and an auxiliary cover braided around said auxiliary core. This auxiliary cover comprises 16 braided strands (i.e., knitted on a 16-spindle, all-full loom). Each braided strand comprises one multifilament polyester yarn (in particular polyethylene terephthalate) of 90 dtex and one multifilament polyester yarn (in particular polyethylene terephthalate) of 230 dtex. Advantageously, the longline textile core has a linear density of between 0.50 g / meter and 1 g / meter, for example, approximately 0.60 g / meter.

[0165] The elongated core is passed through the solution and then through an extrusion device, in this specific example between two rollers rotating at approximately 2 meters per minute and applying an extrusion pressure of 3 bars. The number of full bath impregnation and extrusion passes is approximately 10.

[0166] The elongated core is air-dried for 24 hours. This produces a first example of an elongated core. C- Overbraiding of a long, thin blanket member

[0167] In general, in examples 1 to 4 below, an empty space is represented on the figures 1 to 4 by a white circle, and a solid spindle is represented by a spindle filled with dots. Example 1 of an implantable device

[0168] A first example of a cover member is overbraided, according to the first arrangement example 10 shown in the figure 1 around the elongated core 20 covered obtained at point B. The figure 1This represents the arrangement of the spindles of a 16-spindle braiding loom. In this specific example, a first group of 6 adjacent solid spindles 32 is separated from a second group of 6 adjacent solid spindles by two empty spindles 36 and 38, respectively. Each solid spindle supports 6 multifilament polyethylene terephthalate yarns of 138 dtex each. This provides the first example of an implantable device according to the invention (EX1). Example 2 of an implantable device

[0169] A second example of a cover member is overbraided, according to the second arrangement example 100 shown in the figure 2 around the elongated core 20 covered obtained at point B. The figure 2This represents the arrangement of the spindles of a 16-spindle braiding loom. In this specific example, a first group of four adjacent solid spindles 42 is separated from a second group of four adjacent solid spindles 44 by first and second groups of four empty spindles each, 46 and 48. Each solid spindle supports six multifilament polyethylene terephthalate yarns, each with a density of 138 dtex. This gives us the second example of an implantable device according to the invention (EX2). Example 3 of an implantable device

[0170] A third example of a cover member is overbraided, according to the third arrangement example 200 shown in the figure 3 around the elongated core 20 covered obtained at point B. The figure 3This represents the arrangement of the spindles of a 24-spindle braiding loom. In this specific example, four groups of three adjacent solid spindles (52, 54, 56, and 58) are separated from each other by a group of three empty spindles (62, 64, 66, and 68). Thus, one group of three solid spindles is surrounded by two groups of three empty spindles each. Each solid spindle supports four 138 dtex polyethylene terephthalate multifilament yarns. This results in the third example of an implantable device according to the invention (EX3). Example 4 of an implantable device

[0171] A fourth example of a cover member is overbraided, according to the fourth arrangement example 300 shown in the figure 4 around the sheathed, elongated core obtained at point B. The figure 4This represents the arrangement of the spindles of a 24-spindle braiding loom. In this specific example, four groups of four adjacent solid spindles (72, 74, 76, and 78) are separated from each other by a group of two empty spindles (82, 84, 86, and 88). Thus, a group of four solid spindles (72, 74, 76, or 78) is surrounded by two groups of two empty spindles (82, 84, 86, and 88). Each solid spindle supports four 138 dtex polyethylene terephthalate multifilament yarns. This results in the fourth example of an implantable device according to the invention (EX4). D- Study of bio-mineralization

[0172] 7500 ml of a simulation body fluid (SBF) is prepared according to the protocol of Tadashi Kokubo and Takadama, Biomaterials, May 1, 2006, 27(15): 2907-15. The reagents are introduced into ultrapure water in this order: NaCl (60.2625g), NaHCO3 (2.6625g), KCl (1.6875g), K2HPO4, 3H2O (1.7325g), MgCl2, 6H2O (2.3325g), 1 Mol / L HCl, CaCl2 (2.19g), Na2SO4 (0.54g). 293 ml of 1 Mol / L HCl is added to adjust the pH to 7.40.

[0173] At least 3 samples of 3 cm in length each for examples EX1, EX2, EX3 and EX4 are immersed in 120ml of the SBF solution according to the equation Vs=Sa / 10, Vs being the volume of SBF and Sa being the surface area of ​​the sample (mm 2< ).

[0174] The incubation times are 1 day (D1), 3 days (D3) and 7 days (D7).

[0175] Samples corresponding to EX4 without bioglass are also implemented as test samples.

[0176] The incubation parameters are 80 rpm, and the temperature of the SBF solution is maintained at 37°C in the shaker. The SBF solution is renewed every 48 hours. E- Characterization of samples from examples 1 to 4 (EX1 to EX4) tested

[0177] Morphological and structural analysis of the samples and surface characterization were performed using a scanning electron microscope (SEM, Hitachi Flex 1000) operating at 5 kV. The tested samples (EX1 to EX4) were rinsed with distilled water and dried. All samples were then sprayed with a thin chromium coating (5 nm thick) on their outer surfaces. The evaluation methodology consisted of analyzing three different sites on the outer surface of the cover member, the inner surface of the cover member, and the outer surface of the elongated core.

[0178] Chemical characterization of the surface samples was performed by energy-dispersive X-ray spectroscopy (EDS). Diffraction pattern acquisition was carried out on the PAnalytical X'Pert Pro MRD diffractometer, with a copper anode as the X-ray source (characteristic wavelength of 1.5418 Å). Diffractograms were obtained in the 5° to 70° (theta) range using a detector (PANalytical X'Celelerator®) equipped with 0.5° and 1° anti-divergence slits and a 10 mm mask. F- In vitro cytotoxicity study

[0179] A cytotoxicity study was carried out on examples EX1 to EX4 according to the ISO 10993-5 standard, dating from 2009. This proved positive, that is to say that the survival rate of living cells is satisfactory. G- Comments

[0180] There figure 5represents a SEM photograph of the outer surface of the long-spanning core 20 obtained at point B. Arrows F1 and F2 point to the formation of bioglass crystals after 7 days of incubation in the SBF.

[0181] At the end of 1 day and 3 days of incubation, the absence of bio-mineralization is noted according to the external surface of the long-slender core 20, according to the internal surface or the external surface of the covering member of examples 1 to 4.

[0182] After 7 days of incubation, a slight bio-mineralization is observed on the outer surface of the covering members of examples 3 and 4 near the through orifices.

[0183] Significant bio-mineralization is observed on all internal surfaces of the cover members of examples 1 to 4 after 7 days of incubation.

[0184] In particular, it is noted that a greater number of bioglass crystals are present on the outer surface of the cover member of example 4 shown in the figure 8 that according to the outer surface of the cover member of example 3 shown in the figure 6 However, the through-holes in examples 3 and 4 advantageously allowed the bio-mineralization of the outer surface of the covering member.

[0185] As can be seen on the figure 7 Calcium and phosphorus are present in abundance on the outer surface of the long core (IB) and on the inner surface of the cover member (IF) of example 3. Calcium and phosphorus are also found again on the outer surface of the cover member (EF) of example 3.

[0186] By calculating the molar ratio between calcium and phosphorus, we find a Ca / P ratio after 7 days of incubation of 1.125 according to the outer surface of the cover member of example 3, and of 1.75 according to the outer surface of the cover member of example 4.

[0187] The molar ratio of hydroxyapatite is estimated to be 1.67.

[0188] Finally, more bio-mineralization is observed after 14 or 21 days of incubation for examples 1 to 4.

[0189] Advantageously, the implantable device according to the invention ensures the mechanical function of tendon or ligament but also allows the progressive release of functional agent(s), in particular allows the formation of hydroxyapatite on the outer surface of the covering limb, in particular from 7 days for examples 3 and 4.

Claims

1. An implantable device, in particular for the reconstruction of an anterior cruciate ligament or tendon, comprising an elongate core (20) and a hollow elongate covering member comprising an inside volume at least partially receiving said elongate core, the hollow elongate covering member comprises through-holes in fluid communication with said inside volume, characterized in that said elongate core comprises a polymer matrix bio-erodible in an aqueous medium and one or more functional agent(s), in that the elongate core (20) comprises a textile elongate core at least partially coated with the bio-erodible polymer matrix within which the functional agent(s) are dispersed, in that the hollow elongate covering member is a hollow braid, and in that the functional agent(s) comprise(s) one or more osteoinductive and / or osteoconductive agents and / or the functional agent(s) are chosen from among: anti-inflammatories, antibiotics, antibacterials, analgesics and a mixture thereof.

2. The implantable device according to claim 1, characterized in that the osteoinductive and / or osteoconductive agent(s) are chosen from among: bioglass, calcium phosphate-based bioceramics, in particular hydroxyapatites, and tricalcium phosphate, and a mixture thereof.

3. The implantable device according to either one of claims 1 and 2, characterized in that the elongate core (20) comprises a braid.

4. The implantable device according to any of claims 1 to 3, characterized in that the textile elongate core comprises an auxiliary core comprising one or more yarn(s), and an auxiliary textile covering braided around said auxiliary core.

5. The implantable device according to any of claims 1 to 4, characterized in that the bio-erodible polymer matrix comprises a polymer, or several mixed polymers, that are dehydrated and able to form a soluble gel in an aqueous medium, in particular bio-erodible.

6. The implantable device according to any of claims 1 to 5, characterized in that the bio-erodible polymer matrix comprises one or more bio-erodible polymers chosen from among the following polymers: (co)polymers of cyclodextrin(s) and / or of derivative(s) of cyclodextrin(s) and / or of inclusion complex(es) of cyclodextrin(s) and / or of derivatives of soluble cyclodextrin(s); collagen polymers; polymers derived from hyaluronic acid; polymers of carboxymethylcellulose or derivatives of carboxymethylcellulose; vinyl polymers such as polyvinylpyrrolidone polymers (PVP) or polyvinylpolypyrrolidone polymers (crospovidone); polyethylene glycol polymers; lactic acid polymers; copolymers of lactic acid and polyethyleneglycol (PLLA / PEG); copolymers of lactic acid, glycolic acid and polyethyleneglycol (PLGA / PEG); polymers of polyvinyl alcohols (PVA); and polymers of polyacrylates such as polyhydroxyethylmethacylate (PHEM); and a mixture thereof.

7. The implantable device according to any of claims 1 to 6, characterized in that the bio-erodible polymer matrix comprises a polymer chosen from among: polyvinylpyrrolidone polymers (PVP); polyvinyl alcohol polymers; (co)polymers of cyclodextrin(s) and / or derivative(s) of cyclodextrin(s) and / or of inclusion complex(es) of cyclodextrin(s) and / or of soluble cyclodextrin derivative(s).

8. The implantable device according to any of claims 1 to 7, characterized in that the bio-erodible polymer matrix comprises one or more bio-erodible polymers, and in that the weight ratio of functional agent(s) / bio-erodible polymer(s) in the polymer matrix, in particular the weight ratio of osteoinductive and / or osteoconductive fillers / bio-erodible polymer(s) in the polymer matrix, is higher than or equal to 0.2 and lower than or equal to 1.8; preferably higher than or equal to 0.2 and lower than or equal to 1.

9. The implantable device according to any of claims 1 to 8, characterized in that the hollow elongate covering member comprises a braid comprising between 8 and 30 braided threads, and in that each braided thread comprises between 2 and 8 yarns, preferably said yarns each have a titer of between 80 dtex and 200 dtex.

10. The implantable device according to any of claims 1 to 9, characterized in that the hollow elongate covering member comprises between 30 and 120 yarns, preferably between 30 yarns and 80 yarns, in particular said yarns are not bioresorbable.

11. The implantable device according to any of claims 1 to 10, characterized in that the mass fraction of the bio-erodible polymer matrix comprising the functional agent(s) in said implantable device is higher than or equal to 5 % and lower than or equal to 25%, preferably higher than or equal to 10% and lower than or equal to 20%.

12. The implantable device according to any of claims 1 to 11, characterized in that the mass fraction of the elongate core, free of the polymer matrix and of said functional agent(s), and of said hollow elongate covering member, measured relative to the total mass of the implantable device, is higher than or equal to 50%, preferably higher than or equal to 75%.

13. The implantable device according to any of claims 1 to 12, characterized in that the hollow elongate covering member is a hollow braid with a substantially constant braiding angle greater than or equal to 2 mm and smaller than or equal to 15 mm, preferably greater than or equal to 4 mm and smaller than or equal to 10 mm.

14. A method for manufacturing an implantable device, in particular according to any of claims 1 to 13, characterized in that it comprises: a) a step to apply a bio-erodible polymer coating, comprising one or more functional agents, at least in part onto an elongate textile core, b) an over-braiding step of a hollow elongate covering member around at least in part of said at least partially coated textile elongate core; c) a step to recover an implantable device comprising an elongate core comprising a textile elongate core and a hollow elongate covering member comprising an inside volume at least partially receiving said elongate core, said elongate core comprises a polymer matrix bio-erodible in an aqueous medium coating at least partially said textile elongate core, and one or more functional agents dispersed in the bio-erodible polymer matrix, in that the covering member comprises through-holes in fluid communication with said inside volume, and in that the functional agent(s) comprise one or more osteoinductive and / or osteoconductive agents and / or the functional agent(s) are chosen from among: anti-inflammatories, antibiotics, antibacterials, analgesics and a mixture thereof.

15. The manufacturing method according to claim 14, characterized in that step b) is a step of braiding a hollow braid on a braiding device comprising a total number of spindles higher than or equal to 12 and lower than or equal to 30, and in that the number of empty spindles (36,38,46,48,62,64,66,68,82,84,86,88) is higher than or equal to 10% and lower than or equal to 60% of the total number of spindles, in particular higher than or equal to 20% and lower than or equal to 60% of the total number of spindles.

16. The manufacturing method according to either one of claims 14 and 15, characterized in that step b) is a braiding step of a hollow braid on a braiding device comprising filled spindles (32,34,42,44,52,54,56,58,72,74,76,78) and empty spindles (36,38,46,48,62,64,66,68,82,84,86,88), and in that the filled spindles (52,54,56,58,72,74,76,78) are distributed in at least three groups of filled spindles in which each group comprises adjacent filled spindles, and in that a group of filled spindles is separated from another group of filled spindles by at least one empty spindle (62,64,66,68,82,84,86,88), preferably by at least two or three empty spindles.

17. The manufacturing method according to claim 16, characterized in that the braiding device comprises three or four groups of three or four adjacent filed spindles, and three or four groups of adjacent empty spindles, a group of adjacent filled spindles being arranged between two groups of adjacent empty spindles.

18. The manufacturing method according to any of claims 14 to 17, characterized in that step b) is a braiding step of a hollow braid at a substantially constant braiding angle greater than or equal to 2 mm and smaller than or equal to 15 mm, preferably greater than or equal to 4 mm and smaller than or equal to 10 mm.

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