MEDICAL DEVICE COMPRISING A CELL-FREE BIOLOGICAL MATRIX AND AT LEAST ONE POLYMER

Description

Technical field

[0001] The invention relates to a particular medical device comprising a biological matrix, as well as its manufacturing method and its use. State of the art

[0002] Many surgical applications require the reinforcement of soft tissues with elements combining mechanical strength, flexibility and biological compatibility.

[0003] For this purpose, biological matrices are increasingly used for the manufacture of medical devices due to their biological compatibility. However, in the case of septic or potentially septic surgeries, biological implants can be digested and degraded due to an excessive enzymatic load (collagenases in particular), which makes their use unsuitable for many applications.

[0004] WO 2016 / 014119 A1 and WO 2016 / 094166 A1 disclose a medical device comprising an acellular extracellular matrix and a polymer selected from hydroxybutyrates and other PHAs. The polymer is used as a protective coating to control enzymatic degradation of the matrix.

[0005] There is therefore a need for biological implants that exhibit optimal mechanical integrity and reinforcement during tissue reconstruction, even in the event of infections. The objective of the invention is to meet this need. Summary of the invention

[0006] To this end, the invention relates to a medical device comprising at least one acellular biological matrix and at least one polymer, in particular at least one acellular biological matrix partially or totally covered by at least one layer comprising at least one polymer, as defined in the claims.

[0007] Advantageously, the presence of at least one polymer with the acellular biological matrix makes it possible to make the biological matrix resistant to infections, while retaining the qualities of the biological matrix in terms of mechanical resistance, flexibility and biological compatibility. It can thus be used for medical applications, particularly in surgery.

[0008] The invention also relates to a method for manufacturing such a medical device. The method comprises implementing the following steps: preparation of a cellular biological matrix so as to allow the adhesion of a solution comprising at least one polymer, by a chemical and / or mechanical and / or electrochemical and / or physical surface treatment, and partial or total coating of the acellular biological matrix with a solution comprising at least one polymer.

[0009] Other features and advantages will emerge from the detailed description of the invention which follows. Detailed description of the invention Definitions

[0010] By “acellular” biological matrix within the meaning of the invention is meant a biological matrix in which the cellular elements have been eliminated by a decellularization process with the aim of destroying and / or removing the cells and their components from the extracellular matrix of the biological matrix while maintaining its structure and properties. Indeed, for a biological matrix to be able to be implanted in a recipient, it must be decellularized so as to reduce its immunogenicity.

[0011] For the purposes of the invention, “Allograft” or “allograft” means a biological matrix, a graft, originating from a donor belonging to the same biological species as the recipient.

[0012] For the purposes of the invention, “Implant” means a medical device used in surgery.

[0013] For the purposes of the invention, “biological matrix” means a biomaterial derived from the human or animal species.

[0014] For the purposes of the invention, "P4HB" means a particular PHA which stands for Poly-4-hydroxybutyrate. It is a homopolymer of a 4-hydroxybutyrate unit.

[0015] "Peel test" is used here to refer to a test to determine the adhesion strength between two materials. Each material is placed in pneumatic jaws at a given pressure and then separated at a constant speed as specified in the examples.

[0016] For the purposes of the invention, “PHAs” means polyhydroxyalkanoates which are biodegradable polyesters.

[0017] For the purposes of the invention, “solution” means a homogeneous mixture resulting from the dissolution of one or more solute(s) in a solvent.

[0018] By "Suture Retention Force" or "Suture Retention Strength" as used herein is meant a test for determining the force (N) required to pull a suture out of a specimen.

[0019] For the purposes of the invention, "Uniaxial tensile strength" means a test for determining the tensile strength of the specimen under test. The properties measured are Ultimate Tensile Strength, breaking force and elongation at break.

[0020] For the purposes of the invention, “Viscosity” means a property of resistance to the flow of a fluid for a flow without turbulence.

[0021] For the purposes of the invention, the term “xenograft” means a biological matrix, a graft, originating from a donor belonging to a biological species different from that of the recipient. Medical device

[0022] According to a first aspect, the invention therefore aims at a medical device comprising: at least one acellular biological matrix, and at least one polymer, characterized in that the acellular biological matrix has been prepared before coating with the polymer, so as to allow the adhesion of a polymer solution, by a chemical and / or mechanical and / or electrochemical and / or physical surface treatment.

[0023] Acellular biological matrices include a broad class of biomaterials extracted from grafts of various origins.

[0024] Preferably, the biological matrix in the medical device according to the invention is of human and / or animal origin.

[0025] According to a particularly suitable embodiment, it is a biological matrix chosen from biological matrices of porcine, bovine, equine, caprine, fish origin and their mixtures.

[0026] The biological matrix according to the invention can be chosen from all animal and / or human biological matrices, preferably from one of the following biological matrices: dermis, intestinal submucosa, aorta, bladder, amniotic membrane, peritoneum, pericardium, dura mater, tendons, bones, cartilage and mixtures thereof.

[0027] The biological matrix of the medical device according to the invention is acellular. There are many known methods for obtaining an acellular biological matrix. The methods used may be enzymatic and / or based on chemical solutions and / or relying on mechanical methods. The method used must be a method for obtaining an acellular biological matrix suitable for use in surgery, particularly for the reconstruction of soft tissues.

[0028] The acellular biological matrix according to the invention is preferably an acellular biological matrix which has at least one of the following characteristics, even more preferably all of them: Uniaxial Tensile Strength greater than or equal to 5N / mm2 for a 5mm x 50mm specimen with thickness taken into account in the calculation. Each end is clamped in pneumatic jaws lengthwise 1cm from each edge. The edge separation speed is 30mm / min. Uniaxial Tensile Strength is reported by dividing the maximum force (N) / (5 (mm) x thickness (mm)). Suture Retention Force greater than or equal to 5N for a 1cm x 1cm specimen using a suitable suture (type 4-0 polypropylene) threaded 3mm from the edge of the specimen at its center, the opposite side being clamped in a pneumatic jaw approximately 5mm away. Both ends of the suture are clamped in the lower jaw. The jaw separation speed is 20mm / min. The maximum force (N) is retained.

[0029] Preferably, the biological matrix used has the specifications defined in the applicable standards (“USP official monographs” latest version, ASTM) according to the type of biological matrix used.

[0030] The acellular biological matrix of the device according to the invention can be of varied shape. Preferably it: is dry, preferably it has a residual moisture content of between 10% and 18%, and / or it has a surface appearance improving the adhesion of at least one polymer, in particular the adhesion of at least one solution of polymer(s). This surface appearance is obtained by treatment / preparation of the acellular biological matrix before coating, in particular by chemical and / or mechanical and / or electrochemical and / or physical surface treatment.

[0031] The polymer present in the medical device according to the invention may be any type of polymer suitable for use as a medical device and in particular as a surgical implant.

[0032] The polymer(s) present in the device according to the invention are preferably chosen from the following polymers: poly(glycolides), poly(lactide-co-glycolides); polylactic acid, polyglycolic acid, poly(lactic acid co glycolic acids), polycaprolactones, poly(orthoesters), polyanhydrides, poly(phosphazenes), polyhydroxyalkanoates (including in particular P4HB and poly-3-hydroxybutyrate-co-3-hydroxy valerate (PHBV)), polyesters, poly(lactide-co-caprolactones), polycarbonates, tyrosine polycarbonates, polyamides, polyesteramides, poly(dioxanones), poly(alkylene alkylates), polyethers, polyvinyl pyrrolidones or PVP, polyurethanes, polyetheresters, polyacetals, polycyanoacrylates, poly(oxyethylene) / poly(oxypropylene) copolymers, polyacetals, polyketals, polyphosphates, polyphosphoesters, polyalkylene oxalates, polyalkylene succinates, acids polymaleic, chitin, chitosan, and mixtures thereof.

[0033] According to a particularly suitable embodiment, the device according to the invention comprises at least one PHA and even more preferably a PHA chosen from at least P4HB, P4HB copolymers and their mixtures. PHAs constitute a family of materials produced by numerous microorganisms. For example, US patent 6,316,262 from the company Meta-bolix, Inc. of Cambridge MA, USA, which describes a method for obtaining a biological system for producing polyhydroxyalkanoate polymers containing 4-hydroxyacids, can be cited. US patents 6,245,537, US 6,623,748, US 7,244,442 and US 8,231,889 also describe methods for producing PHAs suitable for medical use and for medical devices according to the invention.

[0034] Preferably, PHA and in particular P4HB and / or its copolymers have a low level of endotoxins, in particular they allow for a level of less than 20 EU per medical device. Preferably, the device comprises at least one acellular biological matrix partially or totally covered by at least one layer comprising at least one polymer.

[0035] The device according to the invention may comprise one or more acellular biological matrices, one or more layers of polymer(s) and possibly other constituents. The medical device according to the invention may comprise, for example, at least one acellular biological matrix partially or totally covered by at least two layers comprising at least one polymer.

[0036] According to a particular embodiment, the medical device consists exclusively of an acellular biological matrix partially or totally covered by a layer comprising at least one polymer.

[0037] According to another particular embodiment, the medical device is constituted exclusively by an acellular biological matrix partially or totally covered by two layers comprising at least one polymer.

[0038] The presence of the polymer(s) in the medical device allows optimal reinforcement during tissue reconstruction supported by the biological matrix, even in the event of infection.

[0039] The polymer layer(s) may comprise one or more channels which allow the incorporation, during use in surgery, of elements promoting optimal reconstruction of the tissues in which the device is used as an implant (PRP, stem cells, antibiotics, etc.). These channels may be circular or non-circular. They preferably have an internal surface area of between 0.007 mm 2< and 0.8 mm 2< . They may be obtained by printing a shape in the biological matrix by pressing before coating the biological matrix. The shape is then removed after coating and drying. Manufacturing process

[0040] The medical device according to the invention can be obtained by any suitable method. In particular, the invention relates to a method for manufacturing a medical device comprising the implementation of the following steps: preparation of a cellular biological matrix so as to allow the adhesion of a solution comprising at least one polymer, by a chemical and / or mechanical and / or electrochemical and / or physical surface treatment, and partial or total coating of the acellular biological matrix with a solution comprising at least one polymer.

[0041] The preparation step of the cellular biological matrix consists of a chemical and / or mechanical and / or electrochemical and / or physical surface treatment. This may be, for example, a treatment by abrasion and / or milling and / or microtexturing and / or laser and / or UV.

[0042] The biological matrix must be prepared in such a way as to allow the adhesion of a solution of polymer(s). The suitably prepared biological matrix can have different shapes (round, square, circular, irregular ...), flat or raised, with channels, with one of the textured surfaces, be of regular or irregular thickness.

[0043] In a preferred embodiment, the biological matrix must be dry or dried so as to have a residual moisture content of the order of 10% to 18%. The residual moisture content is preferably measured using a desiccator such as the Halogen Moisture Analyzer from Mettler Toledo.

[0044] A drying technique used is preferably that of “Loss on Drying” (loss on drying) described in USP 41 (“scaffold bovine dermis” bovine dermis): 1- an empty aluminum cup is placed in the device and the tare is carried out, 2 the cup is filled with a sample of 1.0 g + / - 0.2 g cut into pieces of 4 mm 2< , 3 the heating program at 130°C is launched 4 when the weight no longer varies over a given time, the result is displayed in %.

[0045] Another conventional oven drying method can also be used. In this case, an aluminum dish previously weighed empty is filled with a sample of 5.0 g + / - 0.2 g cut into 4 mm 2< pieces. The whole is placed at 100°C for 16 hours. The whole is then weighed and the "loss on drying" is calculated: dry matter % = [(weight of dry extract + cup (g) - weight of cup (g)) / g of sample] x 100 humidity % = 100 - dry matter %.

[0046] The prepared biological matrix is then used as a support for coating with a polymer solution.

[0047] Preferably, the solution comprising at least one polymer has been previously obtained by solubilizing the dry polymer(s) in at least one solvent, preferably at least one polar solvent.

[0048] The polymer(s) must in fact preferably be converted into a solution suitable for coating using the appropriate solvent.

[0049] When the polymer is a PHA and in particular P4HB and / or one of its copolymers, the solvent is preferably chosen from the following polar solvents: dichloromethane, chloroform, tetrahydrofuran, dioxane, acetone and their mixtures.

[0050] In a preferred embodiment, the P4HB is solubilized in an acetone solution, preferably in a ratio of 5% to 25% (w / w). The respective quantities are brought together, the whole is heated and maintained at a temperature below the boiling point of acetone (approximately 56°C) until the P4HB is completely dissolved and the desired viscosity of at least 10%, more preferably 15% and even more preferably 20% (w / w) is obtained. Preferably, after solubilization of the polymer(s) in a solvent, the polymer solution is degassed and / or debubbled to purge the mixture of air bubbles. Preferably, the solution is placed under vacuum (minimum -1 bar) for the time necessary for complete degassing / debubbling.

[0051] The step of coating the acellular biological matrix with a solution of polymer(s) is preferably carried out at a temperature lower than or equal to the denaturation temperature of the collagen. In a particularly suitable manner, the coating is carried out at a temperature between 10 and 60°C, preferably between 10 and 50°C, even more preferably between 20 and 50°C.

[0052] The coating can be carried out by any suitable means, preferably by “solvent casting”, “spray coating”, “dip coating”.

[0053] Advantageously, the method according to the invention allows the direct application of a solution of polymer(s) at the desired concentration on a previously prepared acellular biological matrix and it is not necessary to first manufacture a polymer film or sheet and then place it on the support in order to allow the elements to adhere to each other by heating. When carried out by "solvent casting", the coating can be carried out with different technologies: "knife", "double side", commabar, "case knife", "engraved roller", "2 roller", "3 roller combi", "micro roller", "5 roller", "reverse roller", "rotary screen", "dipping", "slot die", "curtain coating", "hotmelt slot die".The simplest method is based on the use of an Elcometer type casting knife. The biological matrix is placed on a table, depending on the desired thickness and the surface to be treated, the required quantity of polymer solution is placed on the acellular biological matrix. The Gardener Knife is then moved over the acellular biological matrix to uniformly coat the implant. The Gardener Knife has previously been adjusted to a certain height. In order to automate the operation, a coating machine can be used. The polymer solution is pumped through a slot die to be applied to the moving planar biological implant. In a preferred embodiment, the width of the slot die is 600 mm, and the implant advancement speed is 1 - 10 m / min.The pumping speed, the feed rate, the slot die width and the solution concentration can be adjusted to obtain the implant with the desired coating thickness and width.

[0054] When coating is carried out by spray coating, the polymer solution(s) is pumped to a nozzle which projects droplets onto the surface to be treated. This technique is particularly advantageous for the treatment of biological matrices which have 3D shapes (e.g.: biological implants having a hemispherical, ovoid, tubular shape, in the shape of anatomical breast implants, etc.).

[0055] When coating is carried out by "Dip coating" (immersion coating), or by dipping, the part to be treated is dipped into a dissolved, melted, softened or fluidized powder material in order to cover it with a layer of this material. This technique is particularly advantageous for the treatment of raised and flat biological implants.

[0056] After coating, the medical device obtained is composed of a layer of biological matrix partially or totally coated with at least one polymer in solution, and the whole being then dried and then preferably pressed to obtain a uniform thickness.

[0057] In a preferred embodiment, the acellular biological matrices coated with the polymer solution(s) are placed in an oven or furnace or heating chamber to allow complete evaporation of the solvent. At a temperature between 0°C and 50°C, between 15 and 40°C, preferably 30°C plus or minus 5°, so as to avoid excessively rapid evaporation and deformation of the biological matrix.

[0058] According to a variant, the acellular biological matrices coated with the polymer solution(s), optionally before or after drying, are pressed in a hydraulic press for a period of 30 to 60 s, between 6 bars and 200 bars, in particular between 50 and 200 bars and at a temperature between 50°C and 190°C, in particular between 50°C and 100°C. The flat biological matrices (and consequently the medical devices according to the invention) are treated in a hydraulic press between 2 plates. The biological matrices (and consequently the medical devices according to the invention) in relief (such as biological implants treated by said method in the form of breast implants of anatomical or hemispherical shapes) can be pressed into molds having the desired impressions (such as a “molding machine for fabric cup” (bra cup press). Uses

[0059] The medical device according to the invention can be used for any medical application, in particular as an implant, in particular in surgery. It can be used as such or transformed for use in surgeries.

[0060] In particular and without limitation, the medical devices according to the invention can be used for the following applications: repair, regeneration and replacement of soft and hard tissues, healing device, bandage, patch, dressing, burn dressing, ulcer dressing, skin substitute, hemostatic, tracheal reconstruction device, organ salvage device, dural substitute, dural patch, guide nerve, nerve regeneration or repair device, hernia repair device, hernia mesh, hernia plug, temporary wound or tissue support device, tissue engineering scaffold, guided tissue repair / regeneration device, mesh fixation devices, anti-adhesion membrane, barrier adhesion, tissue separation membrane, retention membrane, sling, pelvic floor reconstruction device, urethral suspension device,urinary incontinence treatment device, bladder repair device, inflation or filling device, rotator cuff repair device, meniscus repair device, meniscus regeneration device, guided tissue regeneration membrane for periodontal tissues, anastomosis device, cell-seeded device, cell encapsulation device, controlled release device, drug delivery device, plastic surgery device, breast lift device, mastopexy device, breast reconstruction device, breast augmentation device, breast reduction device, breast reconstruction devices after mastectomy with or without breast implants, rhinoplasty device.,

[0061] The invention is now illustrated by examples and test results. Examples and test results Example 1: Treatment of acellular biological matrix

[0062] A flat acellular dermal matrix is placed on a numerically controlled machine tool. A 5 mm diameter carbide burr is mounted on the machine tool. A rotation speed of 20,000 to 40,000 rpm is used with a feed rate of 2 m / min. The depth is variable depending on the desired final thickness. Surfacing can be total or only concern a part of the implant in order to delineate shapes. Example 2: Treatment of acellular biological matrix

[0063] A flat acellular dermal matrix is placed on a brushing / carding machine. The implant surface is then treated with cards of the desired diameter (e.g. 105 mm) made of metal wires (e.g. 0.2 mm diameter). Example 3: Treatment of acellular biological matrix

[0064] A flat dermal matrix is placed on a Mercier-Turner type sander. The surface of the implant is sanded with a 240 grit abrasive.

[0065] A section of the abraded implant (6 cm x 6 cm) is coated with approximately 0.02 g / cm 2 of P4HB and pressed for 60 s at 50 bar pressure and 50 ° C (preheated press plates). A "T peel" test is performed. 2 cm x 6 cm specimens are cut. The P4HB coating is separated from the biological implant over a section of 1.5 cm x 2 cm. The 2 pieces thus separated are placed in the pneumatic jaws (45 psi). The coated section of the biological implant is separated at a speed of 25 mm / min. The "T-peel" force is measured over a standardized width of 20 mm and on an average of 5 peaks (loads). On the 3 specimens tested, the adhesion was stronger so that the test did not allow the coated layer to be peeled. Example 4: Treatment of acellular biological matrix

[0066] An acellular dermal matrix is treated with a high-frequency electric field such as Telea Biotech (4-64 MHz) in order to create cavities and / or perforations of 0.6 mm in diameter. Example 5: Treatment of acellular biological matrix

[0067] An acellular dermal matrix is processed as specified in Example 1. A 2 mm carbide burr is mounted on the machine tool to cut sinusoidal channels in the matrix along the length of the matrix. Speed and feed are similar to Example 1. The channels are repeated at regular intervals across the width to cover part or all of the implant. The depth of the channels is a function of the desired final diameter. Alternatively, an impression can be made to press the channels into the matrix. Example 6: example of a “solvent casting” coating process

[0068] An acellular dermal matrix treated according to Example 1 with dimensions of 2 cm x 6 cm or 12 cm 2 < is placed on a table. The desired quantity of P4HB being 0.0164 g / cm 2 < , an 18% (w / w) P4HB / acetone solution is prepared. The necessary quantity is taken and deposited on the implant. The casting knife is then moved by translation on the implant in order to standardize the thickness of the coating. In order to automate the operation, a coating machine can be used. An acetone / P4HB solution is prepared in order to feed the machine. The solution is pumped through a slot die to be applied to the moving flat biological implant. In a preferred embodiment, the width of the slot die is 600 mm, the implant progression speed is 1 - 10 m / min. Example 7: Example of a dip coating process

[0069] An acellular biological matrix treated according to example 4 of 4 cm x 6 cm is immersed by a machine (the implant is placed on a vertical crossbar) in a tank containing an acetone / P4HB solution at the desired concentration. The biological matrix is then extracted from the tank by an upward vertical movement at a speed of 25 mm / min. The density of P4HB obtained by the coating is then 0.02 to 0.04 g / cm 2 < . The parameters (size of the part to be treated, speed of the crossbar, concentration of the solution) are understandable by those skilled in the art in order to obtain the desired coating in the end. Example 8: Example of drying and pressing and characteristics of the medical devices obtained

[0070] A dermal matrix treated according to Example 1 is coated with approximately 0.03g / cm 2< of P4HB and is pressed for 30s at 100 bars of pressure and 50°C (pre-heated press plates). On 3 specimens tested, with an average thickness of 1.35 mm, the average maximum uniaxial tensile strength (UTS) is 26.50 MPa.

[0071] The test is performed on an Instron model 3342 / L2345 measuring bench. The specimen is cut with a bone shape type V cutter as described in the ASTM D -638-5 standard. The piece thus cut is introduced from each end into the pneumatic jaws of the bench (60 psi) leaving a central part of 2.5 cm. A speed of 25 mm / min is applied until the piece breaks. The "uniaxial tensile strength" is reported (max. force / sectional area). A "T peel" test is performed. 2 cm x 6 cm specimens are cut. The P4HB coating is separated from the biological implant over a section of 1.5 cm x 2 cm. The 2 pieces thus separated are placed in the pneumatic jaws (45 psi). The coated section of the biological implant is separated at a speed of 25 mm / min. The “T-peel” force is measured over a standardized width of 20 mm and on an average of 5 peaks (loads).Of the 3 specimens tested, the adhesion was stronger so that the test did not allow the coated layer to peel. Example 9: Example of drying and pressing and characteristics of the medical devices obtained

[0072] Under the same previous test conditions, a dermal matrix treated according to Example 2 is coated with approximately 0.03 g / cm 2< of P4HB and then pressed for 60 s at 200 bar and 100°C resulting in an average UTS max value on 3 specimens of 27.65 MPa. The average test “T-peel” cannot be calculated because the peeling is incomplete. Example 10:

[0073] Under the same previous test conditions, a dermal matrix treated according to Example 3 and coated with approximately 0.03 g / cm 2< of P4HB then pressed for 30 s at 100 bars and 100°C, results in an average UTS max value on 3 specimens of 33.07 MPa.

Claims

1. A medical device comprising at least one acellular biological matrix covered in whole or in part by at least one layer comprising at least one polymer, characterized in that the acellular biological matrix has been prepared prior to polymer coating, so as to allow the adhesion of a polymer solution, by chemical and / or mechanical and / or electrochemical and / or physical surface treatment.

2. The medical device according to the preceding claim, characterized in that it consists of an acellular biological matrix covered in whole or in part by a layer comprising at least one polymer.

3. The medical device according to in claim 1, characterized in that the acellular biological matrix is covered in part or in whole by at least two layers comprising at least one polymer.

4. The medical device according to in claim 1, characterized in that it consists of an acellular biological matrix covered in part or in whole by two layers comprising at least one polymer.

5. The medical device according to one of the preceding claims, characterized in that the acellular biological matrix is of human and / or animal origin.

6. The medical device according to the preceding claim, characterized in that the acellular biological matrix of animal origin is selected from among the acellular biological matrices of porcine, bovine, equine, caprine, or fish origin, and mixtures thereof.

7. The medical device according to one of the preceding claims, characterized in that the acellular biological matrix is selected from one of the following biological matrices: dermis, intestinal submucosa, aorta, bladder, amniotic membrane, peritoneum, pericardium, dura mater, tendons, bones, cartilage, and mixtures thereof.

8. The medical device according to any one of the preceding claims, characterized in that the polymer(s) are selected from among the following polymers: polyhydroxyalkanoates, poly(glycolides), poly(lactide-co-glycolides), polylactic acid, polyglycolic acid, poly(lactic acid-co-glycolic acids), polycaprolactones, poly(orthoesters), polyanhydrides, poly(phosphazenes), polyesters, poly(lactide-co-caprolactones), polycarbonates; tyrosine polycarbonates, polyamides, polyesteramides, poly(dioxanones), poly(alkylene alkylates), polyethers, polyvinyl pyrrolidones, polyurethanes, polyether esters, polyacetals, polycyanoacrylates, poly(oxyethylene), copolymers of poly(oxypropylene), polyacetals, polyketals, polyphosphates, polyphosphoesters, polyalkylene oxalates, polyalkylene succinates, polymaleic acids, chitin, chitosan, and mixtures thereof.

9. The medical device according to one of the preceding claims, characterized in that the polymer(s) are selected from among the following polyhydroxyalkanoates: P4HB, co-polymers, and mixtures thereof.

10. The medical device according to one of the preceding claims, characterized in that the acellular biological matrix: - has a residual moisture content of between 10% and 18%..

11. A method for manufacturing a medical device according to one of the preceding claims, characterized in that it comprises carrying out the following steps: - preparation of an acellular biological matrix so as to allow the adhesion of a solution comprising at least one polymer, by chemical and / or mechanical and / or electrochemical and / or physical surface treatment. - partial or total coating of the acellular biological matrix with a solution comprising at least one polymer.

12. The method for manufacturing a medical device according to the preceding claim, characterized in that the coating is performed at a temperature lower than or equal to the denaturation temperature of the collagen.

13. The method for manufacturing a medical device according to the preceding claim, characterized in that the coating is performed at a temperature between 10 and 60°C.

14. The method for manufacturing a medical device according to one of claims 11 to 13, characterized in that the biological matrix is dried so as to have a residual moisture content of between 10% and 18%.

15. The method for manufacturing a medical device according to one of claims 11 to 14, characterized in that the coating is carried out by solvent casting, spray coating, or dip coating.

16. The method for manufacturing a medical device according to one of claims 11 to 15, characterized in that the solution comprising at least one polymer was obtained beforehand through solubilization of the polymer(s) in at least one polar solvent.

17. The method for manufacturing a medical device according to the preceding claim, characterized in that, after solubilization of the polymer(s), the solution is degassed and / or debubbled under vacuum in order to purge the mixture of air bubbles.

18. The method for manufacturing a medical device according to one of claims 11 to 17, characterized in that the polymer solution comprises at least P4HB dissolved in an acetone solution.