Biocompatible and bioresorbable porous solid for the fabrication of surgical implants

Abstract

Biocompatible and bioresorbable porous solid for the fabrication of surgical implants. The invention relates to a porous solid containing at least 90% by weight, relative to the total weight of the porous solid, of a polyester-polyurethane copolymer. The invention also relates to the method for preparing said porous solid. The invention further relates to a medical implant material consisting of a porous solid and collagen, as well as a method for its preparation. The invention also relates to a medical implant made of a medical implant material. Finally, the invention relates to the use of the porous solid or the medical implant material for the fabrication of a medical implant. Figure for the abstract: Fig. 5.

Description

Title of the invention: Biocompatible and bioresorbable porous solid for the fabrication of surgical implants technical field

[0001] The invention relates to the preparation of a biocompatible copolymer, as well as the use thereof for the preparation of a porous solid of biocompatible copolymer intended for use in the manufacture of a surgical implant, such as a meniscal implant for example. Previous technique

[0002] The invention relates to the technical field of surgical implants designed to repair or at least partially replace tissue such as a meniscus, cartilage of the tibia, hip, shoulder or ankle, for example.

[0003] The knee is an essential joint in daily life. This joint connects the femur (whose end is rounded) to the tibia (whose end is flat). The menisci act as stabilizers and shock absorbers between these two bones, whose shapes are not complementary. They allow these bones to fit together properly and glide smoothly against each other, thus preventing premature wear of the cartilage. The menisci are themselves made of cartilaginous tissue.

[0004] The menisci are fragile and can crack, tear, and wear down over the years. When a meniscus is significantly damaged due to trauma or natural wear and tear, a total or partial meniscectomy may be necessary. One of the essential functions of the menisci is to distribute the load in the knee, and the absence of menisci in one of the compartments, whether lateral or medial, can cause short-term pain and long-term osteoarthritis.

[0005] To address this problem, meniscus transplantation is still rarely used because the patient must be young and without advanced osteoarthritis. Furthermore, a transplant requires a meniscus from a compatible donor. However, meniscus transplants can be performed arthroscopically in severe knee osteoarthritis, when the meniscal tissue is generally destroyed. Combined with other procedures—such as knee alignment or realignment, stabilization or stabilization, micro-drilling of osteoarthritic areas, release of the lateral ligament of the injured compartment for decompression, and cell therapy—these transplants allow for the regeneration of cartilage covering the chondral lesions at the condyle-tibial level. The meniscal shock absorber enables this regeneration and provides long-term protection, thus avoiding the need for knee replacement, particularly in active patients with good physical performance.

[0006] Another solution is the meniscal implant, designed to replace all or part of the damaged meniscus. Such a meniscal implant must be biocompatible, non-toxic, and must not generate toxic degradation products. In order to fulfill its role, the meniscal implant must also exhibit good mechanical properties: good mechanical strength, tear resistance, and flexibility to act as a shock absorber. The meniscal implant must also be porous to facilitate tissue regeneration from a vascularized portion of the meniscus. Finally, the meniscal implant must be bioresorbable, with a rate of absorption adapted to the implant's colonization by cartilage.

[0007] The two resorbable and synthetic meniscal implants developed to date are the Actifit® meniscal implant from Orteq and the Collafit® meniscal implant from Arthrocart Biotech.

[0008] Orteq has described in US patent applications 2007 / 0015894 and 2011 / 0105635 a method for preparing a polyurethane comprising i) obtaining a macrodiol by ring-opening polymerization (e.g., ring-opening of e-caprolactone), ii) reacting the macrodiol with an excess of diisocyanate (in particular 1,4-diisocyanate) to obtain a macrodiisocyanate, and iii) reacting the macrodiisocyanate with a chain extender such as 1,4-butanediol. This document also describes the fabrication of a porous scaffold made with this polyurethane using a porous agent, and its use for preparing an implant. The preparation of the porous polyurethane scaffold is more precisely described in patent application WO 2015 / 134028. The disadvantages associated with these meniscal implants include the use of a toxic diisocyanate and a degradation time that is sometimes too long for good colonization by cartilage.

[0009] Applicant Arthrocart Biotech described in patent application FR 3 082 726 the fabrication of a meniscal implant made from polyurethane and collagen. The use of collagen promotes in vivo collagen production. In patent application EP 3 789 048, the meniscal implant is based on a combination of polymers: a polyurethane, polylactic-co-glycolic acid (PLGA), and urethane polycarbonate (PCA). The polyurethane is obtained by a process comprising the following steps: i) reaction of a diol (typically 1,4-butanediol) with ε-caprolactone to obtain a macrodiol, then ii) reaction of the macrodiol obtained with a diisocyanate to obtain a macrodiisocyanate, and finally reaction of the macrodiisocyanate with a chain extender (typically 1,4-butanediol). The combined use of these polymers makes it possible to strengthen the mechanical resistance of the final material.In patent application WO 2021 / 130418, the production of meniscal implants from a polyester urethane ester copolymer and collagen is described. As previously described, the copolymer is obtained by the reaction of poly(ε-caprolactone) diol, a poly(lactide-co-glycolide) diol, and a (C1-C4) alkyl ester of lysine diisocyanate. The meniscal implants thus obtained have excellent mechanical properties and good porosity, but their flexibility is sometimes insufficient.

[0010] At present, there is a need to provide new medical implants, and in particular meniscal implants, that are porous, have good mechanical properties and good flexibility, have an adequate degradation time to allow colonization by tissues, are not toxic and do not generate toxic degradation products.

[0011] During its research to develop a new medical implant with these properties, the Applicant company was surprised to discover that cross-linking the polymer constituting the implant had an impact on the mechanical properties and flexibility of the final material. More specifically, the incorporation of cross-linked polymer makes it possible to obtain a final material with both good mechanical properties and improved flexibility, which is difficult to reconcile. Advantageously, the material obtained under the invention has good porosity, which facilitates colonization by cartilage. Advantageously, the material thus obtained is non-toxic and does not generate toxic degradation products: it is therefore very well tolerated by the patient. Advantageously, the material thus obtained is bioresorbable; it has a degradation time that is neither too long nor too short, allowing colonization by cartilage.Furthermore, combined use with collagen promotes in vivo collagen production. Description of the invention

[0012] Thus, the present invention relates to a porous solid containing at least 90% by weight of a copolymer I relative to the total weight of the porous solid S, said porous solid S having a porosity of 40% to 95% by volume, preferably 60% to 95% by volume, and an average pore diameter belonging to the range of 25 microns to 500 microns, characterized in that the copolymer I is prepared according to the following steps: 1) to have at least one polyol II, said polyol II being an aliphatic polyester polyol or a copolymer thereof, linear (ILL) or branched (ILR), 2) possess at least one aliphatic or cyloaliphatic polyisocyanate III, or a dimer or trimer thereof, linear IIIL or branched IILR, 3) have at least one IV polyol prepolymer, linear IV-L or branched IV-R, the IV polyol prepolymer being an aliphatic polyester polyol or an aliphatic polyester polyol copolymer, 4) react at least one polyol II with at least one polyisocyanate III, in order to obtain a macropolyisocyanate V, 5) react macropolyisocyanate V with at least one polyol prepolymer IV, the molar percentage of reactive functions in at least one branched polyol (II-R), at least one branched polyisocyanate (III-R) and at least one branched polyol prepolymer (IV-R) relative to polyol (II), polyisocyanate (III) and polyol prepolymer (IV) being greater than 0% and less than or equal to 50%.

[0013] The porous solid according to the invention further exhibits one or more of the following characteristics, or a combination thereof:

[0014] - the molar percentage of reactive functions of branched ILR polyol, of branched polyisocyanate III-R and branched polyol pre-polymer IV-R compared to polyol II, polyisocyanate III and polyol pre-polymer IV belongs to the range of 0.1 to 50%, preferably 0.2 to 45%, preferably 0.5 to 35% and better still 1 to 20%;

[0015] - the copolymer I is prepared according to the following steps: 1) have at least one polyol II, said polyol II being an aliphatic polyester polyol or a copolymer of aliphatic polyester polyol, linear ILL or branched ILR, 2) have at least one aliphatic or cyloaliphatic diisocyanate IILL, or a dimer or trimer thereof, 3) have at least one linear diol prepolymer IV-L, which is a linear aliphatic polyester diol or a linear aliphatic polyester diol copolymer, and have at least one branched polyol prepolymer IV-R, which is a branched aliphatic polyester polyol, or a branched aliphatic polyester polyol copolymer, comprising at least three hydroxyl groups, 4) react at least one polyol II with at least one diisocyanate III, in order to obtain a macropolyisocyanate V, 5) react macrodiisocyanate V with a mixture of at least one linear diol prepolymer IV-L and at least one branched polyol prepolymer IV-R;

[0016] - the molar ratio of reactive functions of the linear diol prepolymer IV relative to to the reactive functions of the branched polyol prepolymer (V) in the mixture in step 5) ranges from 99:1 to 50:50, preferably from 98:2 to 60:40, and more preferably from 95:5 to 75:35;

[0017] - in step 2), polyisocyanate III is a linear diisocyanate IILL-a of formula: oCN'A'7\œ(IILL-a) with M representing an alkylene group (CLC10), cyclic or acyclic, possibly interrupted by at least one urea group (-NH-CO-NH-), and possibly substituted by one or more alkyl groups (CLC6), and / or one or more COOR1 groups with RI representing an alkyl group (CLC4), and / or one or more COOH groups;

[0018] - in step 2), the polyisocyanate III is a linear diisocyanate III selected from: (III-L-4), and preferably diisocyanate III is lysine III- ethyl ester diisocyanate L-3;

[0019] - the polyol II is chosen from poly(e-caprolactone) diol, poly(lactic-co-glycerol) colic) linear or branched polyol or poly(lactide-co-glycolide) linear or branched polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers, preferably the initiator polyol II is poly(e-caprolactone) diol;

[0020] - the linear polyol prepolymer IV-L is selected from poly(e-caprolactone) diol, linear poly(lactic-co-glycolic) diol or linear poly(lactide-co-glycolide) polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers;

[0021] - the linear polyol prepolymer IV-L has the following formula: r%r%(iv-Li), with : - A representing a group of the following formulas, in which x and y are equal or different and independently represent an integer from 2 to 30, preferably from 10 to 30, more preferably from 12 to 20: - L1 representing a linear (C1-C10) alkylene group possibly substituted by a (C1-C6) alkyl group or by a (C1-C6) alkyl ether group; ethylene glycol; diethylene glycol; triethylene glycol; polyethylene glycol; or an (Cl-CIO) alkylene group, possibly substituted by a (Cl-C6) alkyl group or a (C1-C6) alkyl ether group, and interrupted by a benzene;

[0022] - L1 represents a linear (C1-C10) alkylene group, possibly substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and preferably such that L1 represents (CH2)W with w representing an integer from 1 to 6, and preferably 3;

[0023] - the IV-R branched polyol prepolymer has the following formula: with : - A representing a group of the following formulas, in which x and y are equal or different and independently represent an integer from 2 to 30, preferably from 10 to 30, more preferably from 12 to 20: î Î1 (A), ' g " K - L2 representing a linear or branched (Cl-CIO) alkylene group, or cycloalkylene group in which one or more CH2s may be replaced by O, substituted by at least one (CH2)z-OA group with z being an integer greater than or equal to 1, possibly substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and possibly interrupted by a benzene; or a benzene group substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1 and possibly substituted by an (C1-C6) alkyl group or by an (Cl-C6) alkyl ether group;

[0024] - L2 is substituted by one, two, three, four, five or six (CH2)Z-OA groups with z being an integer greater than or equal to 1;

[0025] - the linear polyol pre-polymer IV-L and the branched polyol pre-polymer IV-R have each with an average number molar mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol;

[0026] - the macropolyisocyanate V obtained in step 4) has an average molar mass in number ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol;

[0027] - the porous solid S has a bending force belonging to the range of 0.1 MPa at 5 MPa; and

[0028] - the porous solid S is biocompatible and bioresorbable.

[0029] The invention also relates to a method for preparing a porous solid according to the invention, comprising solubilizing the copolymer I in a solvent to obtain a solution of copolymer I, followed by evaporating said solvent.

[0030] The process for preparing the porous solid according to the invention further has one or more of the following characteristics, or a combination thereof:

[0031] - the process further comprises suspending a porogenous agent in the copolymer solution I;

[0032] - the process includes cooling the copolymer solution I before the evaporation of the solvent; and

[0033] - the process includes heating the copolymer I to a temperature greater than or equal to its melting point, then its cooling.

[0034] The invention further relates to a medical implant material consisting of porous solid S according to the invention, or obtained according to the process according to the invention, and collagen.

[0035] The medical implant material according to the invention has one or more of the following characteristics, or a combination thereof:

[0036] - the collagen is recombinant human collagen;

[0037] - the porous solid S is covered by collagen;

[0038] - collagen covers the periphery of the porous solid S, and the pore walls of the porous solid S;

[0039] - the medical implant material is biocompatible and bioresorbable; and

[0040] - the medical implant material has an in vivo degradation time of less than one year.

[0041] The invention also relates to the method of preparing a material for a medical implant according to the invention. This method comprises immersing the porous solid S according to the invention or obtained according to the method according to the invention in collagen, or injecting or vaporizing collagen onto it.

[0042] The invention also relates to a medical implant made of a medical implant material according to the invention, or of a medical implant material obtained according to the process according to the invention. The medical implant may be, for example, a meniscal implant, a condylar cartilage implant, a tibial cartilage implant, a hip cartilage implant, a shoulder cartilage implant, or an ankle cartilage implant.

[0043] Next, the invention relates to the use for the production of a medical implant of the copolymer according to the invention or obtained according to the process according to the invention, or of the porous solid of copolymer according to the invention or obtained according to the process according to the invention, or of the material for medical implant according to the invention or obtained according to the process according to the invention.

[0044] Finally, the invention relates to a kit comprising the porous solid according to the invention or the porous solid S obtained according to the process according to the invention, or comprising the medical implant material according to the invention or the medical implant material obtained according to the process according to the invention. Brief description of the drawings

[0045] [Fig.1] The [Fig.1] is the 'H NMR spectrum of PLGA1.

[0046] [Fig.2] The [Fig.2] is the *H NMR spectrum of PLGA*2.

[0047] [Fig.3] The [Fig.3] is the 'H NMR spectrum of PLGA*3.

[0048] [Fig.4] The [Fig.4] is the 'H NMR spectrum of PLGA*4.

[0049] [Fig.5] Fig.5 is a reproduction of the images obtained by scanning electron microscopy of the porous solids SP11 ([Fig.1].A), CP2 ([Fig.1].B) and CP6 ([Fig.1].C). Description of the implementation methods

[0050] The invention relates to a porous solid S comprising at least 90% by weight, relative to the total weight of the porous solid S, of a copolymer I, and preferably at least 95% by weight, even better at least 98% by weight, and more preferably at least 99% by weight. According to a particular embodiment, the porous solid S consists exclusively of the copolymer I.

[0051] Advantageously, the porosity of the porous solid S is homogeneous, that is to say, it is continuous. In other words, the porous solid does not include a non-porous zone, or a zone with variable porosity: the value of the porosity is substantially identical at every point of the porous solid S, that is to say, it varies by less than 5%, preferably by less than 3%, preferably by less than 2%, more preferably by less than 1%, and even better by less than 0.5%.

[0052] The porous solid S is porous, that is to say, it comprises pores. Pores are cavities delimited by walls. Advantageously, the porosity of the porous solid S is open, that is to say, it forms a network of interconnected pores in three dimensions. Thus, when the porous solid S is used for the fabrication of a medical implant, this allows for colonization by cartilage, for example.

[0053] The porosity of the porous solid S, which corresponds to the total volume of interconnected voids (pores) present in the material in question, is a physical quantity between 0% and 100%. For the porous solid S to be used as a medical implant, the porosity must be at least 40% by volume to ensure sufficient tissue colonization, and at most 95% by volume to ensure that the mechanical properties of the porous solid are satisfactory for the intended application as a medical implant. The porosity value can vary depending on the intended medical implant and can be determined by those skilled in the art, using techniques that will be detailed below. Generally speaking, in order to use the porous solid for the manufacture of a medical implant, its porosity falls within the range of 40 to 95% by volume, preferably 60 to 95%, and even better 80 to 95%.

[0054] The porosity of a porous body can be measured by determining the volume of a liquid contained within said porous body by weighing said material before and after prolonged immersion in said liquid (water or other solvent). Knowing the respective densities of the material considered and the liquid used, the mass difference, converted into volume, is directly representative of the volume of the pores and therefore, the total porosity of the porous body. Thus, the porosity can be calculated using the following equation 1, in which m is the mass of the sample (in g), V is the volume of the sample (in cm3), and ρ is the density of the sample (in g / cm3):

[0055] [Math. 1] (1) m P = 1 --- X 100 p V

[0056] Alternatively, porosity can be determined by tomography.

[0057] The average diameter of the pores of the porous solid S belongs to the range from 25 microns to 500 microns, preferably from 50 microns to 400 microns, and more preferably from 100 microns to 300 microns.

[0058] By mean pore diameter, we mean the value d50 of a volumetric distribution for which 50% of the total pore volume corresponds to the volume of pores with a diameter less than d50. The volumetric distribution is the curve (analytical function) representing the frequencies of the pore volumes as a function of their diameter. d50 corresponds to the median separating the frequency curve into two equal parts. In the context of the present invention, the mean pore diameter was determined by scanning electron microscopy.

[0059] The porous solid comprises essentially, or even exclusively, a copolymer I, which is a polyester polyurethane. In the context of the invention, copolymer I is a copolymer obtained according to the process comprising the following successive steps:

[0060] 1) have at least one polyol II as defined below, and preferably a polyol II,

[0061] 2) have at least one polyisocyanate III as defined below, and preferably one or two polyisocyanates III,

[0062] 3) have at least one polyol IV prepolymer as defined below, and preferably one or two

[0063] 4) react at least one polyol II with at least one polyisocyanate III, in order to to obtain a macropolyisocyanate V, or a mixture of macropolyisocyanates III,

[0064] 5) react the macropolyisocyanate(s) V with at least one polyol prepolymer IV.

[0065] By "polyol" is meant a molecule, a pre-polymer or a polymer comprising at least two hydroxyl (OH) functions.

[0066] In the context of the invention, a "pre-polymer" means an oligomer or a polymer comprising reactive functional groups capable of participating in a polymerization reaction. The pre-polymer comprises at least two reactive functional groups. For example, a diol pre-polymer is a pre-polymer comprising two functional groups. reactive hydroxyl (OH) groups. The reactive functions are preferably terminal, although this is not mandatory.

[0067] In the context of the invention, a "macropolyisocyanate" is a macromolecule comprising several isocyanate (NCO) groups. In the context of the invention, a "macrodiisocyanate" is a macromolecule comprising two isocyanate (NCO) groups.

[0068] In step 5), the molar ratio of isocyanate reactive functions in macrodiisocyanate V: hydroxyl reactive functions in the polyol pre-polymer(s) IV can range from 1.2 to 1, and preferably from 1.05 to 1. According to a particularly advantageous embodiment of the invention, the molar ratio of isocyanate reactive functions in macrodiisocyanate V: hydroxyl reactive functions in the polyol pre-polymer(s) IV is 1.

[0069] In the context of the invention, the molar ratio of isocyanate reactive functions in macrodiisocyanate V to hydroxyl reactive functions in polyol pre-polymer(s) IV is determined by the ratio of the number of moles of isocyanate reactive functions in macrodiisocyanate V to the number of moles of hydroxyl reactive functions in polyol pre-polymer(s) IV.

[0070] In the context of the invention, the number of moles of reactive functional groups (FGs) in a molecule is determined by the number of moles of said molecule multiplied by the number of reactive functional groups (FGs) in said molecule. For example, the number of moles of reactive functional groups in an alkanediol corresponds to the number of moles of the alkanediol multiplied by 2. In the case of a polymer or prepolymer, the dispersity D is not equal to 1, meaning that the chain lengths and the number of reactive functional groups, when present, are not all identical in the sample considered.Also, in a common practice, the number of reactive functions FG of a polymer or prepolymer can be determined by 'H NMR, using an internal standard whose chemical shifts integrated by 'H NMR in reference are different from those of the hydrogen(s) of the polymer or prepolymer integrated(s) to determine the number of reactive functions (typically the hydrogen(s) in the alpha position of the reactive function), and using equation 2 below: .

[0071] [Math. 2] (2) _ WX NH6q(P) XJ ref mr^xNHei}(re^xfP

[0072] with:

[0073] - Nfg(p) representing the number of FG reactive functions of a polymer or pre polymer P, expressed in g. eq ',

[0074] - mp representing the mass of the analyzed polymer or pre-polymer sample P, in g,

[0075] - Nh eq (P) representing the number of hydrogens in the alpha position of the function reactive FG in the polymer or pre-polymer P,

[0076] - representing the integration of the 'H NMR signal of the hydrogen(s) used as a reference in the internal standard,

[0077] - mref representing the mass of the internal standard, in g,

[0078] - Nh eq (ref) representing the number of hydrogens used as a reference in the internal standard,

[0079] - Jp representing the integration of the *H NMR signal of the hydrogen(s) in position alpha of the reactive function FG in the polymer or pre-polymer P.

[0080] The internal standard can be chosen by a person skilled in the art, based on the chemical shifts of the different protons of the analyzed polymer or prepolymer. Benzophenone or trioxane can be cited as examples of suitable internal standards.

[0081] The contents of internal standard, and of polymer or pre-polymer are determined by a person skilled in the art.

[0082] In the context of the invention, polyisocyanate III is an aliphatic or cyloaliphatic polyisocyanate, or a dimer or trimer thereof. Polyisocyanate III may be a linear polyisocyanate IIIL or a branched polyisocyanate IILR. Here, "linear polyisocyanate IIIL," "linear diisocyanate IIIL," "polyisocyanate IIIL," and "diisocyanate IIIL" have the same meaning and are used interchangeably. A branched polyisocyanate IILR comprises at least three isocyanate groups.

[0083] In the context of the invention, linear polyisocyanate IILL advantageously has the following formula according to a first embodiment:

[0084] [Chem. 1] y (IILL-a), cor xNco

[0085] with M representing an alkylene or cycloalkylene group, optionally interrupted by at least one urea group (-NH-CO-NH-), and optionally substituted by one or more alkyl groups, and / or one or more carboxylic acid ester groups, and / or one or more COOH groups.

[0086] By "alkyl," we mean a saturated hydrocarbon chain that may be linear or branched. By "cycloalkyl," we mean a cyclic alkyl group.

[0087] By "alkylene" is meant a divalent alkyl group. By "cycloalkylene" is meant a cyclic alkylene group, that is to say a divalent cycloalkyl group.

[0088] According to a first embodiment, M represents a (C1-C10) alkylene group, cyclic or acyclic, optionally substituted by one or more groups selected from (C1-C6) alkyl groups and COOR1 groups, with RI representing a (C1-C4) alkyl group. Advantageously, the isocyanate functions of the III-L diisocyanate are terminal, although this is not mandatory.

[0089] According to a particular embodiment, M represents an acyclic, branched or linear (C1-C10) alkylene group, optionally substituted by one or more groups selected from (C1-C6) alkyl groups and COOR1 groups, with RI representing a (C1-C4) alkyl group. By way of particularly preferred examples, 1,4-butanediisocyanate III-L-1, hexamethylene diisocyanate III-L-2, and (C1-C6) alkyl lysine ester diisocyanates, such as ethyl lysine ester diisocyanate III-L-3, of formulas such as those detailed below, may be used as III-L diisocyanates, in mixtures or, preferably, alone.

[0090] [Chem. 2]

[0091] [Chem. 3] œr(III-L-2),

[0092] [Chem. 4] (III-L-3). A x OCN' yv

[0093] According to a particular embodiment of the invention, M represents a (C1-C6) alkylene group, and preferably according to this embodiment, polyisocyanate III is selected from 1,4-butanediisocyanate III-L-1, hexamethylene diisocyanate III-L-2, and mixtures thereof. According to another particular and preferred embodiment of the invention, polyisocyanate III is a diisocyanate of (C1-C6) alkyl lysine ester, preferably lysine ethyl ester diisocyanate III-L-3, and more particularly L-lysine ethyl ester diisocyanate, advantageously used alone. The copolymer obtained from lysine ethyl ester diisocyanate IILL-3 has the advantage of being better tolerated by the patient than those obtained from 1,4-butanediisocyanate III-Ll or hexamethylene diisocyanate IILL-2.Indeed, the copolymer obtained from lysine III-L-3 ethyl ester diisocyanate degrades in vivo, releasing lysine, and is therefore very well tolerated by the patient.

[0094] According to a second embodiment, M represents a (C1-C10) alkylene group, cyclic or acyclic, interrupted by at least one urea group (-NH-CO-NH-), optionally substituted by one or more groups selected from COOH, (C1-C6) alkyl groups and COOR1 groups, with RI representing a (C1-C4) alkyl group. Preferably according to this embodiment, M represents a (Cl-ClO) group. alkylene, cyclic or preferably acyclic, interrupted by at least one urea group (-NH-CO-NH-), optionally substituted by one or more COOH and / or COOR1 groups, with RI representing a (C1-C4) alkyl group. In particular, according to this embodiment, the linear diisocyanate may have the following III-L-4 formula:

[0095] [Chem. 5]

[0096] According to one embodiment, the linear diisocyanate III-L is selected from the linear diisocyanates III-L-1, III-L-2, III-L-3 and III-L-4.

[0097] In the context of the invention, according to a first embodiment, the branched III-R polyisocyanate advantageously has the following III-R-1 formula:

[0098] [Chem. 6] (III-R-1),

[0099] with:

[0100] - Representative Ml:

[0101] [Chem. 7]

[0102] with x' and y' being identical or different and independently representing an identical or different integer, and independently ranging from 2 to 30, preferably from 10 to 30, better still from 12 to 20,

[0103] - M2 representing a linear or branched (C1-C10) alkylene group, or cycloalkylene in which one or more CH2 groups may be replaced by O, substituted by at least one (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO group, with v being an integer greater than or equal to 0, preferably an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and optionally interrupted by a benzene ring; or a benzene group substituted by at least one (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH- M3-NC0 with v being an integer greater than or equal to 0, preferably an integer greater than or equal to 1, and optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group,

[0104] - M3 and M3' being identical and different and independently representing one on the other hand, an alkylene or cycloalkylene group possibly substituted by one or more alkyl groups and / or carboxylic acid ester groups, and

[0105] - R4, R4' and R4” being identical or different and independently representing one of the other H or an (C1-C4) alkyl group, and preferably H or CH3.

[0106] According to a preferred embodiment of the invention, M2 is substituted by one, two, three, four, five, or six (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO groups. According to a particular embodiment, M2 is substituted by one, two, or three (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO groups.

[0107] According to a first embodiment, M2 represents a linear or branched (C1-C10) alkylene group, or a cycloalkylene (Cl-ClO) group, in which one or more CH2s may be replaced by O, substituted by at least one (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO group, with v being an integer greater than or equal to 0, preferably an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group. Advantageously, according to this embodiment, M2 represents a linear or branched (Cl-ClO) alkylene group, or a cycloalkylene group, substituted by at least one (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO group, with v being an integer greater than or equal to 0, preferably an an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by a (C1-C6) alkyl ether group. Preferably according to this embodiment, the III-R branched polyisocyanate has the following III-R-2 formula:

[0108] [Chem. 8] O R4' r4 o (III-R-2)

[0109] with:

[0110] - Ml as defined in this description,

[0111] - R5 representing O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO or CH2-O-M1-CH2- CHR4”-O-(CO)-NH-M3-NCO,

[0112] - R6 representing H, CH2-O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO or OCH2C(CH 2-O-M1 -CH2-CHR4' ' -O-(CO)-NH-M3-NCO)3.

[0113] Preferably according to this embodiment, R5 represents O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO and R6 represents H, or R5 represents CH2-O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO and R6 represents CH2-O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO, or R5 represents CH2-O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO and R6 represents OCH2C(CH2-O-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO)3.

[0114] According to a second embodiment, M2 represents a linear or branched (C1-C10) alkylene or cycloalkylene group, of which one or more CH2s may be replaced by O, substituted by at least one (CH2)VO-M1-CH2-CHR4”-O-(CO)-NH-M3-NCO group with v being an integer greater than or equal to 0, preferably an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and interrupted by a benzene ring; or a benzene ring substituted by at least one (CH2)Z-OB group with z being an integer greater than or equal to 1 and possibly substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group.

[0115] Advantageously, M3 and M3' are identical or different and independently represent a (C1-C10) alkylene group, cyclic or acyclic, optionally substituted by one or more groups selected from the (Cl-C6) alkyl groups and the COOR1' groups with RI' representing a (C1-C4) alkyl group.

[0116] According to a particular embodiment of the invention, M3 and M3' are identical or different and independently represent an acyclic, branched or linear (C1-C10) alkylene group, optionally substituted by one or more groups selected from (C1-C6) alkyl groups and COOR1' groups with RI' representing a (C1-C4) alkyl group.

[0117] According to a second embodiment, the III-R branched polyisocyanate is a dimer or a trimer. According to this embodiment, when the branched polyisocyanate is a trimer, it advantageously has the formula III-R-3 shown below:

[0118] [Chem. 9]

[0119] with M3 as defined above.

[0120] Preferably according to this embodiment, the III-R branched polyisocyanate is chosen from the following branched polyisocyanates III-R-4, III-R-5, III-R-6, or a combination thereof:

[0121] [Chem. 10] NCO OCN NCO

[0122]

[0123] [Chem. 11]

[0124]

[0125]

[0126] According to a preferred embodiment, III-R-6 branched polyisocyanate is used alone as III-R branched polyisocyanate. According to a first embodiment, at least one III polyisocyanate is linear, that is to say, only one or more linear III-L polyisocyanates are used, and no branched III-R polyisocyanate. Preferably, according to this embodiment, only one linear III-L polyisocyanate is used. According to a second embodiment, a mixture of at least one linear III-L polyisocyanate and at least one branched III-R polyisocyanate is used, in particular a mixture of a linear III-L polyisocyanate and a branched IILR polyisocyanate. According to this embodiment, the molar percentage of reactive isocyanate functions of the branched (IILR) polyisocyanate(s) in the mixture of at least one linear III-L polyisocyanate and at least one branched IILR polyisocyanate is less than or equal to 50%. In other words, according to this embodiment, the mixture of at least one linear III-L polyisocyanate and at least one branched IILR polyisocyanate comprises a molar ratio of reactive isocyanate functions of the branched (IILR) polyisocyanate per ratio to the reactive isocyanate functions of linear polyisocyanate (III-L) less than or equal to 0.5.

[0127] In the context of the invention, a molar percentage of reactive functions of a first pre-polymer or polymer in a mixture containing the first pre-polymer or polymer and a second pre-polymer or polymer corresponds to the number of moles of reactive functions of the first pre-polymer or polymer divided by the sum of the number of moles of reactive functions of the first pre-polymer or polymer and the number of moles of reactive functions of the second pre-polymer or polymer.

[0128] In the context of the invention, a molar ratio of reactive functions of a first pre-polymer or polymer with respect to the reactive functions of a second pre-polymer or polymer corresponds to the number of moles of reactive functions of the first pre-polymer or polymer divided by the number of moles of reactive functions of the second pre-polymer or polymer.

[0129] In the context of the invention, the polyol IV prepolymer is an aliphatic polyester polyol or an aliphatic polyester polyol copolymer. The polyol IV prepolymer may be a linear IV-L polyol prepolymer or a branched IV-R polyol prepolymer. Here, "linear IV-L polyol prepolymer," "linear IV-L diol prepolymer," "IV-L diol prepolymer," and "IV-L prepolymer" have the same meaning and are used interchangeably. A branched IV-R polyol prepolymer comprises at least three hydroxyl groups.

[0130] In the context of the invention, the linear diol prepolymer IV-L is preferably a linear aliphatic polyester diol. Preferably, the two hydroxyl groups of the linear diol prepolymer IV-L are terminal, although this is not mandatory.

[0131] According to an advantageous embodiment of the invention, the linear diol prepolymer IV-L is selected from poly(ε-caprolactone) diol, linear poly(lactic-co-glycolic) diol or linear poly(lactide-co-glycolide) polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers, and mixtures thereof. Preferably, the linear diol prepolymer IV-L has the following formula IV-L-1:

[0132] [Chem. 13] ^<%(IV-L-1)

[0133] with:

[0134] - A representative:

[0135] [Chem. 14]

[0136] with x and y being identical or different and independently representing an identical or different integer, and independently ranging from 2 to 30, preferably from 10 to 30, better still from 12 to 20, and

[0137] - L1 representing a linear (C1-C10) alkylene group possibly substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group; ethylene glycol; diethylene glycol; triethylene glycol; polyethylene glycol; or an (Cl-CIO) alkylene group, possibly substituted by an (C1-C6) alkyl group or an (C1-C6) alkyl ether group, and interrupted by a benzene.

[0138] Preferably, L1 represents a linear (C1-C10) alkylene group optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group.

[0139] According to a particularly preferred embodiment of the invention, L1 represents (CH2)w with w representing an integer from 1 to 6, and preferably 3. Thus, according to this preferred embodiment, the linear diol prepolymer IV-L has the following formula IV-L-2:

[0140] [Chem. 15]

[0141] The linear diol prepolymer IV-L can be obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of a diol VI, diol VI having the formula HO-L1-OH. Equimolar contents of D,L-lactide and glycolide are advantageously used, although this is not mandatory. The reaction can be carried out in the presence of a metal catalyst.

[0142] The linear diol prepolymer IV-L advantageously has a number-average molar mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol.

[0143] In the context of the invention, the number-average molar mass can be determined by 'H NMR.

[0144] In the context of the invention, the IV-R branched polyol prepolymer is advantageously a branched aliphatic polyester polyol, or a branched aliphatic polyester polyol copolymer, comprising at least three preferably terminal hydroxyl groups. Preferably, the IV-R branched polyol prepolymer has the following formula:

[0145] [Chem. 16] .V%r%(IV-Rl),

[0146] with:

[0147] - A as defined above, and

[0148] - L2 representing a linear or branched (C1-C10) alkylene group, or cycloalkylene of which one or more CH2s can be replaced by O, substituted by at least one group (CH2)z-OA with z being an integer greater than or equal to 1, possibly substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and possibly interrupted by a benzene; or a benzene group substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1 and possibly substituted by an (C1-C6) alkyl group or by an (Cl-C6) alkyl ether group.

[0149] According to a preferred embodiment of the invention, L2 is substituted by one, two, three, four, five, or six (CH2)Z-OA groups. According to a particular embodiment, L2 is substituted by one, two, or three (CH2)Z-OA groups.

[0150] According to a first embodiment of the invention, L2 represents a linear or branched (Cl-C10) alkylene group, or a (C1-C10) cycloalkylene group, in which one or more CH2 groups may be replaced by O, substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by a (C1-C6) alkyl ether group. Advantageously, according to this embodiment, L2 represents a linear or branched (C1-C10) alkylene group, or cycloalkylene group, substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1, optionally substituted by a (Cl-C6) alkyl group or by a (C1-C6) alkyl ether group. Preferably according to this embodiment, the IV-R branched polyol prepolymer has the following IV-R-2 formula:

[0151] [Chem. 17]

[0152] with:

[0153] - A as defined above,

[0154] - R2 representing OA or CH2OA,

[0155] - R3 representing H, CH2OA or OCH2C(CH2OA)3.

[0156] Preferably according to this embodiment, R2 represents OA and R3 represents H, or R2 represents CH2OA and R3 represents CH2OA, or R2 represents CH2OA and R3 represents OCH2C(CH2OA)3.

[0157] According to this first embodiment, the IV-R branched polyol prepolymer can be obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of a polyol of formula VII:

[0158] [Chem. 18] (vn)

[0159] with R2 and R3 as defined above.

[0160] According to this embodiment, equimolar levels of D,L-lactide and glycolide are advantageously used, although this is not mandatory.

[0161] According to a second embodiment, L2 represents a linear or branched (C1-C10) alkylene or cycloalkylene group in which one or more CH2s may be replaced by O, substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1, optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and interrupted by a benzene; or a benzene group substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1 and optionally substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group.

[0162] The IV-R branched polyol prepolymer advantageously has a number-average molar mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol.

[0163] According to one embodiment, the linear diol prepolymer IV-L and the branched polyol prepolymer IV-R are each obtained from equimolar contents of D,L-lactide and glycolide.

[0164] According to an advantageous embodiment of the invention, the linear diol prepolymer IV-L and the branched polyol prepolymer IV-R each have a number-average molar mass ranging from 100 to 10,000 g / mol, preferably from 1,000 to 5,000 g / mol. The linear diol prepolymer IV-L and the branched polyol prepolymer IV-R may have identical or different molar masses.

[0165] In the context of the invention, polyol II is an aliphatic polyester polyol or a copolymer thereof. Polyol II may be a linear ILL polyol or a branched ILR polyol. Here, "linear ILL polyol," "linear ILL diol," or "ILL diol" have the same meaning and are used interchangeably. A branched ILR polyol comprises at least three hydroxyl groups.

[0166] According to a first embodiment of the invention, polyol II is identical to linear diol prepolymer IV-L or branched polyol prepolymer IV-R, as detailed above. In other words, polyol II can be identical to linear diol prepolymer IV as detailed above, and is then a linear ILL polyol. Alternatively, polyol II can be identical to branched polyol prepolymer IV-R as detailed above, and is then a branched ILR polyol.

[0167] According to a second embodiment, the polyol II is different from the linear diol prepolymer IV-L and the branched polyol prepolymer IV-R. According to this embodiment, the hydroxyl groups of the polyol II are advantageously terminal.

[0168] Regardless of the embodiment, polyol II can be chosen from among the possible polyols for the linear diol prepolymer IV-L and the branched polyol prepolymer IV-R, mentioned above.

[0169] According to one embodiment of the invention, polyol II is selected from poly(ε-caprolactone) diol, linear or branched poly(lactic-co-glycolic) polyol, or linear or branched poly(lactide-co-glycolide) polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers.

[0170] According to an advantageous embodiment of the invention, polyol II is poly(e-caprolactone) diol, preferably having a number molar mass from 200 g / mol to 3000 g / mol, preferably from 1000 g / mol to 3000 g / mol.

[0171] According to a particular embodiment of the invention, one or more polyols II, as detailed below, may be used alone or in mixtures. Preferably, a single polyol II is used for the preparation of copolymer I.

[0172] In step 4), an equimolar mixture of reactive hydroxyl functions of polyol II and reactive isocyanate functions of polyisocyanate III may be used, although a slight excess of reactive isocyanate functions may be used, and in particular a molar ratio of reactive isocyanate functions of polyisocyanate III / reactive hydroxyl functions of polyol II ranging from 1 / 1 to 1.05 / 1.

[0173] The macropolyisocyanate V, obtained by the reaction of polyol II with polyisocyanate III in step 4), advantageously has a number-average molar mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol.

[0174] According to a preferred embodiment of the invention, the porous solid S comprises at least 90% by weight of copolymer I relative to the total weight of the porous solid, the copolymer I being obtained according to the process comprising the following successive steps:

[0175] 1) have at least one polyol II, said polyol II being an aliphatic polyester polyol or an aliphatic polyester copolymer polyol, linear (II-L) or branched (II-R), as defined below, and preferably a polyol II,

[0176] 2) have at least one aliphatic or cyloaliphatic III-L diisocyanate, or a dimer or trimer thereof, as defined above, and preferably a diisocyanate IIIL,

[0177] 3) have at least one linear IV-L diol prepolymer, and preferably a linear diol prepolymer IV-L, which is a linear aliphatic polyester diol or a linear aliphatic polyester diol copolymer as defined above, and having at least one branched polyol prepolymer IV-R, and preferably a branched polyol prepolymer IV-R, which is a branched aliphatic polyester polyol, or a branched aliphatic polyester polyol copolymer, having at least three hydroxyl functions, as defined above,

[0178] 4) react the polyol II with the diisocyanate III, in order to obtain a macrodiisocyanate

[0179] 5) react the macrodiisocyanate with a mixture of at least one pre-polymer linear diol IV-L and at least one branched polyol prepolymer IV-R.

[0180] According to this embodiment, macropolyisocyanate III is a macrodiisocyanate.

[0181] According to this embodiment, in step 5), the molar percentage of reactive functions of the IV-R branched polyol prepolymer in the mixture of IV-L linear diol prepolymer and IV-R branched polyol prepolymer is advantageously less than or equal to 50%, preferably less than or equal to 45%, more preferably less than or equal to 40% and even better less than or equal to 35%.

[0182] Advantageously according to this embodiment, in step 5), the molar percentage of reactive functions of the IV-R branched polyol prepolymer in the mixture of IV-L linear diol prepolymer and IV-R branched polyol prepolymer is greater than or equal to 0.1%, preferably greater than or equal to 0.2%, more preferably greater than or equal to 0.5% and even better greater than or equal to 1%.

[0183] Advantageously, according to this embodiment, the molar percentage of reactive functions of the IV-R branched polyol prepolymer in the mixture of IV-L linear diol prepolymer and IV-R branched polyol prepolymer is in the range of 0.1 to 50%, preferably 0.2 to 45%, even better 0.5 to 40%, and more preferably 1 to 45%. In other words, in step 5) according to this embodiment, the molar ratio of reactive functions of IV-L linear diol prepolymer: IV-R branched polyol prepolymer in the mixture is from 99:1 to 50:50, preferably from 98:2 to 55:45, preferably from 95:5 to 60:40, and more preferably from 90:10 to 75:35.

[0184] According to this embodiment, polyol II is advantageously a linear ILL polyol. In this case, the mixture of linear diol prepolymer(s) IV-L and branched polyol prepolymer(s) IV-R comprises a molar percentage of reactive functions of branched polyol prepolymer(s) IV-R less than or equal to 50%, preferably less than or equal to 45%, preferably less than or equal to 40% and even better less than or equal to 35%, and greater than 0% and preferably greater than or equal to 0.1%, preferably greater than or equal to 0.2%, preferably greater than or equal to 0.5% and even better greater than or equal to 1%.

[0185] According to a second embodiment of the invention, the porous solid S comprises at least 90% by weight of copolymer I relative to the total weight of the porous solid, the copolymer I being obtained according to the process comprising the following successive steps:

[0186] 1) have at least one polyol II, and preferably a polyol II, as defined below- above,

[0187] 2) have at least one IILR branched polyisocyanate, possibly in mixture with at least linear polyisocyanate IILL, as defined above,

[0188] 3) have at least one polyol IV prepolymer, preferably one or two pre Polyol IV polymers, as defined above,

[0189] 4) react the polyol II with the mixture of linear III-L and branched polyisocyanates III-R, in order to obtain a macropolyisocyanate V,

[0190] 5) react the macropolyisocyanate V with at least one pre-polymer polyol IV.

[0191] According to this second embodiment, at least one polyol II is advantageously a linear polyol II-L.

[0192] According to this second embodiment, at least one pre-polymer polyol IV is advantageously linear pre-polymer polyols IV-L.

[0193] In the context of the invention, the molar percentage of reactive functions of the branched II-R polyol(s), the branched III-R polyisocyanate(s) and the branched IV-R polyol prepolymer(s) relative to the II polyol(s), the III polyisocyanate(s) and the IV polyol prepolymer(s) is greater than 0% and less than or equal to 50%. In the context of the invention, the molar percentage of reactive functions of the branched II-R polyol(s), the branched III-R polyisocyanate(s) and the branched IV-R polyol prepolymer(s) relative to the II polyol(s), the III polyisocyanate(s) and the IV polyol prepolymer(s) corresponds to the molar percentage of reactive functions in the branched prepolymer(s), and is as defined in equation 3 below.

[0194] [Math. 3] . , (3) ^ / / - / 5--^ / / / -^4 / ^-^ ' ■ - ■ J 1¾ :¾ i-

[0195] with:

[0196] - P(ii R + iii R + iv-R) representing the molar percentage of reactive functions in the branched prepolymer(s), i.e. the total molar percentage of reactive functions of branched II-R polyol(s), branched III-R polyisocyanate(s) and branched IV-R polyol prepolymer(s), relative to the prepolymers used for the preparation of copolymer I, namely polyol(s) II (linear II-L and branched II-R), polyisocyanate(s) III (linear III-L and branched III-R) and polyol prepolymer(s) IV (linear IV-L and branched IV-R),

[0197] - n11R representing the number of moles of reactive functions of branched polyol(s) II-R,

[0198] - n111R representing the number of moles of reactive polyisocyanate(s) functions branched III-R,

[0199] - nlv_R representing the number of moles of reactive pre-polymer(s) functions IV-R branched polyol(s),

[0200] - nu representing the number of moles of reactive functions of polyol(s) II (linear(s) and branched(s)),

[0201] - zero representing the number of moles of reactive polyisocyanate(s) III functions (linear and branched),

[0202] - nlv representing the number of moles of reactive functions of the pre- Polyol(s) IV polymer(s) (linear and branched).

[0203] Preferably, the molar percentage of reactive functions P(hr + Ui-r+iv-r) of branched polyol II-R, branched polyisocyanate III-R and branched polyol pre-polymer IV-R relative to polyol II, polyisocyanate III and polyol pre-polymer IV is greater than or equal to 0.1%, preferably greater than or equal to 0.2%, preferably greater than or equal to 0.5% and even better greater than or equal to 1%.

[0204] Preferably, the molar percentage of reactive functions P(nR + m.R+iv r) of branched polyol II-R, branched polyisocyanate III-R and branched polyol pre-polymer IV-R relative to polyol II, polyisocyanate III and polyol pre-polymer IV is less than or equal to 45%, preferably less than or equal to 35% and even better less than or equal to 20%.

[0205] Preferably, the molar percentage of reactive functions P(hr + iii r + iv r) of branched polyol II-R, branched polyisocyanate III-R and branched polyol pre-polymer IV-R relative to polyol II, polyisocyanate III and polyol pre-polymer IV is in the range of 0.1 to 50%, preferably 0.2 to 45%, better still 0.5 to 35% and more preferably 1 to 20%.

[0206] The invention also relates to the copolymer I obtained at the end of step 5).

[0207] In the context of the invention, the porous solid S is advantageously biocompatible.

[0208] Within the scope of the invention, a material is said to be "biocompatible" if the material as such and its in vivo degradation products do not negatively affect the function of a biological tissue with which they come into contact, do not cause a substantial immune response, injury, sensitivity, irritation, cytotoxicity or genotoxicity.

[0209] In the context of the invention, the porous solid S is advantageously bioresorbable.

[0210] In the context of the invention, a material is said to be "bioresorbable" when it can be naturally resorbed in vivo, that is to say, when placed in vivo in contact with biological tissues, the material is degraded by enzymatic, hydrolytic or other chemical reactions or cellular processes, into by-products which are either integrated into the body or expelled from the body.

[0211] The porous material S advantageously has a bending strength ranging from 0.1 MPa to 5 MPa. The value of the bending strength can be adjusted by those skilled in the art by selecting the content of branched prepolymer(s) (i.e., the branched polyisocyanate(s) III-R, and / or branched polyol(s) IV-R and / or branched polyol(s) II-R) / linear prepolymer(s) (i.e. linear polyisocyanate(s) III-L, and / or linear diol(s) IV-L and / or linear polyol(s) II-L), porosity and average pore diameter in particular.

[0212] Within the scope of the invention, the bending force can be determined using ASTM D790.

[0213] The mechanical properties and degradation rate can be adjusted by a person skilled in the art according to the intended use as an implant, by varying the nature of the pre-polymers, the porosity and the average pore diameter.

[0214] The invention also relates to a method for preparing a porous solid S according to the invention. This preparation method comprises the following steps:

[0215] i) have copolymer I,

[0216] ii) solubilize copolymer I in a solvent to obtain a solution of copolymer I, and

[0217] iii) evaporate the solvent from the copolymer solution I.

[0218] In step i), the copolymer I is as described above. It is obtained via steps 1) to 5) described above.

[0219] In step ii), the solvent is of a nature and present in sufficient quantity to allow the solubilization of copolymer I.

[0220] The solvent may be, for example, a protic or aprotic polar solvent. Non-limiting examples include tetrahydrofuran (THF), chloroform, and dichloromethane.

[0221] In step iii), the solvent is evaporated. This evaporation can be carried out under reduced pressure, according to techniques common to those skilled in the art, which will not be detailed here.

[0222] According to an advantageous embodiment of the invention, the copolymer solution I can be cooled before evaporating the solvent, advantageously under reduced pressure. Preferably, the cooling is carried out until the copolymer solution I has completely solidified. This cooling can, for example, be achieved by immersing a container containing the copolymer solution I in liquid nitrogen.

[0223] According to a preferred embodiment of the invention, the process for preparing the porous solid S includes the use of a porous agent. Indeed, the judicious choice of the porous agent, and in particular the average diameter of the particles of this porous agent and the quantity introduced of this porous agent, makes it possible to adjust and better control the porosity and the average diameter of the pores of the porous solid S.

[0224] The porogenic agent must be inert with respect to the compounds present in the copolymer I solution, i.e., it must not react with the copolymer I or with the solvent in particular. The porogenic agent must be slightly or not at all soluble in the solvent present in the copolymer I solution.

[0225] The pore-forming agent may be in the form of a powdered solid with particles whose average diameter is substantially the same as that of the average pore diameter of the resulting porous solid. Advantageously, the average particle diameter of the pore-forming agent ranges from 25 microns to 500 microns, preferably from 100 to 300 microns.

[0226] The content of porogenic agent used depends on the desired final porosity, and can be determined by a person skilled in the art.

[0227] Examples of porogenous agents that may be used include NaCl, CaCl2, sodium citrate, sugars such as glucose, fructose, dextrose, maltose and sucrose and mixtures thereof.

[0228] Thus, when a porous agent is used, the process for preparing a porous solid S then comprises the following steps:

[0229] i) have the copolymer I as defined above,

[0230] i-2) have a porogenous agent in the form of a powdery solid with particles having an average diameter ranging from 25 microns to 500 microns, and as defined above,

[0231] i-3) have a solvent available, the copolymer I being soluble in said solvent and the agent porogen being slightly or not at all soluble in said solvent, the solvent being as defined above,

[0232] ii) solubilize the copolymer I in the solvent and suspend the porogen in the solvent to obtain a suspension of copolymer I and porogen, and

[0233] iii) evaporate the solvent from the copolymer solution I.

[0234] In step i), the copolymer I is as described above. It is obtained via steps 1) to 5) described above.

[0235] In step ii), the preparation of the copolymer I and porogen suspension in the solvent can be carried out in one step (addition of solvent to a mixture of copolymer I and porogen), or in two steps (preparation of a copolymer I solution in solvent and then addition of the porogen to the solution), or in several steps (preparation of a copolymer I solution in solvent, preparation of a porogen suspension in the solvent, and mixing of the copolymer solution and the porogen suspension). Preferably, step ii) comprises the prior preparation of a copolymer I solution, followed by the addition of the pore-forming agent preferably in powder form, i.e. not suspended in the solvent.

[0236] As previously stated, evaporation in step iii) can be carried out under reduced pressure and / or preceded by cooling of the suspension advantageously until complete solidification.

[0237] The process may also include a step (iv), subsequent to step (iii), of washing the copolymer with a non-solvent. Copolymer I is not soluble in the non-solvent, while the porogenic agent is soluble in the non-solvent. This step then allows the removal of any porogenic agent that may be present in the porous solid.

[0238] According to another embodiment, the process for preparing the porous solid S comprises the following steps:

[0239] a) have the copolymer I as defined above,

[0240] b) possess a porogenous agent as defined above,

[0241] c) heating a mixture of copolymer I and porogen to a temperature greater than or equal to the melting temperature of copolymer I, so that it is in a molten state, and

[0242] d) cooling of the mixture.

[0243] As before, the process according to this embodiment may include a subsequent step to step d), of washing the copolymer with a non-solvent, as defined above.

[0244] In step a), the copolymer I is as described above. It is obtained via steps 1) to 5) described above.

[0245] The invention also relates to a porous solid S obtained in accordance with any one of the processes for preparing a porous solid S according to the invention mentioned above.

[0246] The invention also relates to a medical implant material comprising, and preferably consisting of, porous solid S according to the invention, or porous solid obtained according to a process according to the invention, and collagen. Although not preferred, the implant material may further comprise biologically active agents.

[0247] The collagen used may be such as that described in patent application WO 2021 / 130418. In particular, the collagen may be human collagen (e.g. collagen taken from the patient intended to receive the implant) or non-human collagen (e.g. bovine), or a combination thereof.

[0248] In the context of the invention, the collagen is advantageously recombinant human collagen. Recombinant human collagen can be produced by genetically modified plants, in particular by tobacco, rapeseed, maize, pea, tomato, carrot, wheat, barley, potato, soybean, sunflower, lettuce, rice, alfalfa and / or beet plants.

[0249] Collagen can be type I or II collagen, or a combination thereof.

[0250] The collagen implemented in the invention may be a combination of several collagens mentioned above.

[0251] Preferably, the collagen used in the context of the invention is recombinant human collagen, preferably derived from tobacco plants.

[0252] The collagen content in the medical implant material can range from 0.1 to 40% by weight relative to the total weight of the medical implant, preferably from 0.2 to 30%, better still from 0.2 to 20%, and in particular from 0.2 to 10%.

[0253] In the medical implant material, the porous solid S is coated with collagen. More specifically, the collagen may be located at the periphery of the porous solid and / or the collagen may coat the pore walls of the porous solid. Preferably, the collagen coats both the periphery of the porous solid S and the pore walls of the porous solid S: the porous solid is then impregnated with collagen.

[0254] Collagen not only facilitates colonization of the implant by cartilaginous tissues (improved cell colonization because the cells are in contact with collagen and not with the copolymer, which improves their affinity with the material), but also promotes the production of collagen in vivo.

[0255] In the context of the invention, the medical implant material is advantageously biocompatible.

[0256] In the context of the invention, the medical implant material is advantageously bioresorbable. Advantageously, the medical implant material according to the invention has an in vivo degradation time of less than one year.

[0257] The invention also relates to the method for preparing the medical implant material according to the invention. This method comprises a first step consisting of disposing of the porous solid S according to the invention, or of the porous solid S obtained according to the method according to the invention, and a second step of applying collagen to this porous solid S.

[0258] The application of collagen in the second step can be carried out by either of the methods described below, or a combination thereof:

[0259] - immersion of the porous solid S in collagen: the porous solid S is fully immersed in collagen, so that collagen then covers the entire peripheral surface of the porous solid as well as the pore walls of the porous solid S,

[0260] - injection of collagen into the porous solid: collagen is forced to pass into through the porous solid by applying pressure or reduced pressure, so that collagen then covers the entire peripheral surface of the porous solid as well as the pore walls of the porous solid S,

[0261] - Collagen vaporization onto the porous solid: the collagen is vaporized onto the porous solid S, in order to cover all or part of the peripheral surface of the porous solid S,

[0262] - chemical grafting, for example with a grafting agent such as glutaraldehyde or carbodiimide CMC, for example.

[0263] - thermal grafting, for example at a temperature ranging from 50 °C to 150 °C, for a period ranging from 1h to 24 h.

[0264] Preferably, the application of collagen is done by immersing the porous solid S in collagen.

[0265] The invention further relates to a medical implant made of a medical implant material according to the invention, or obtained according to a process according to the invention. The implant may be in the form of a molded body, preferably a molded body whose shape is suitable for use as an implant. The shape therefore depends on the intended application.

[0266] The shape of the implant is obtained:

[0267] - either during the preparation of the porous solid S: the solution or suspension of Copolymer I is then placed, before the solvent evaporates, in a mold whose cavity and dimensions are approximately those of the implant to be produced.

[0268] - either after formation of the porous solid S: the porous solid S is cut into the shapes and desired dimensions before the application of collagen.

[0269] The medical implant can then be of various shapes. In view of the nature of the material for medical implant according to the invention, the medical implant according to the invention can in particular be a meniscal implant, a condylar cartilage implant, a tibial cartilage implant, a hip cartilage implant, a shoulder cartilage implant, or an ankle cartilage implant.

[0270] Furthermore, the invention relates to the use of the porous solid S according to the invention or of the porous solid S obtained in accordance with the process according to the invention, or of the medical implant material according to the invention or of the medical implant material obtained in accordance with the process according to the invention, for the production of a medical implant.

[0271] Finally, the invention relates to a kit comprising the porous solid according to the invention, or the porous solid obtained according to the process according to the invention. According to this embodiment, the kit may further contain collagen, as described above, in sufficient quantity to allow the practitioner to coat the porous solid with collagen. The collagen and the porous solid are not in contact within the kit.

[0272] The invention also relates to a kit comprising the medical implant material according to the invention, or obtained according to the process according to the invention.

[0273] Regardless of the kit, the medical implant material or porous solid, and possibly the collagen, it contains are stored under sterile conditions and / or Inert conditions. Sterilization can be carried out using any technique known to those skilled in the art. Inert conditions typically include a nitrogen atmosphere. This packaging allows for the preservation and storage of medical implant material or porous solids, and possibly collagen, at atmospheric temperature and pressure. Examples

[0274] Example 1: Synthesis of a linear IV-L diol prepolymer (PLGA1)

[0275] The linear diol prepolymer PLGA1 was obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of Sn(Oct)2 and initiated by 1,3-propanediol.

[0276] D,L-lactide and glycolide were purchased from Corbion (Gorinchem, Netherlands) and placed overnight under reduced pressure before use. An equimolar mixture (0.15 mol) of D,L-lactide and glycolide was placed in a flask under a flow of nitrogen at a temperature of 130 °C. Once the monomers had melted, 1,3-propanediol (0.02 mol, >98%, commercially available from Sigma Aldrich) and Sn(Oct)2 (0.5 mol% relative to 1,3-propanediol) were added. The reaction mixture was stirred for 3 h at 130 °C. After the reaction mixture had cooled to room temperature, 50 mL of THF followed by 500 mL of cold heptane (at a temperature of approximately 0 °C) were added. PLGA1 was recovered by filtration and then dried under reduced pressure at 25°C for 24 hours. PLGA1 was thus isolated with a yield of 90%.The 'H NMR spectrum (obtained using a Bruker Avance III HD 400 MHz NMR spectrometer equipped with a BroadBand Inverse (BBI) probe) of PLGA1 is reproduced in [Fig.1].

[0277] Example 2: Synthesis of IV-R branched diol prepolymers (PLGA*2, PLGA*3 and PLGA*4)

[0278] Example 2.1: PLGA*2 branched diol prepolymer

[0279] PLGA*2 was obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of Sn(Oct)2 and initiated by glycerol.

[0280] The procedure is the same as that described for PLGA1 in Example 1 except for the use of glycerol (0.02 mol, commercially available from Sigma Aldrich) instead of 1,3-propanediol. PLGA*2 was thus isolated with a yield of 87%.

[0281] PLGA*2 was analyzed by NMR (Bruker Avance III HD 400 MHz NMR spectrometer equipped with a BroadBand Inverse (BBI) probe for ¹³C NMR, and Bruker Avance III 500 MHz NMR spectrometer equipped with a 5 mm ¹³C BBO Helium cryoprobe and a Bruker Avance III 600 MHz NMR spectrometer for ¹³C NMR). The ¹³C NMR spectrum is reproduced in [Fig. 2]. The NMR analysis determined that PLGA*2 was terminated by 70% lactic acid and 30% by of glycolic acid, and that PLGA*2 had an equivalent weight for a hydroxyl function of 1200 g.eq1.

[0282] Example 2.2: PLGA*3 branched diol prepolymer

[0283] PLGA*3 was obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of Sn(Oct)2 and initiated by pentaerythritol.

[0284] The procedure is the same as that described for PLGA1 in Example 1 except for the use of pentaerythritol (0.02 mol, marketed by Sigma Aldrich) instead of 1,3-propanediol. PLGA*3 was thus isolated with a yield of 83%.

[0285] PLGA*3 was analyzed by NMR (Bruker Avance III HD 400 spectrometer) MHz NMR equipped with a BroadBand Inverse (BBI) probe for ¹H NMR, and a Bruker AVANCE III 500 MHz NMR spectrometer equipped with a 5 mm ¹H / X BBO Helium cryoprobe and a Bruker Avance III 600 MHz NMR spectrometer for ¹³C NMR). The ¹H NMR spectrum is reproduced in [Fig. 3]. NMR analysis determined that PLGA*3 was terminated by 57% lactic acid and 43% glycolic acid, and that PLGA*3 had a hydroxyl group equivalent weight of 933 ± 14 g.eq.

[0286] Example 2.3: PLGA*4 branched diol prepolymer

[0287] PLGA*4 was obtained by ring-opening polymerization of D,L-lactide and glycolide in the presence of Sn(Oct)2 and initiated by dipentaerythritol.

[0288] The procedure is the same as that described for PLGA1 in Example 1 except for the use of dipentaerythritol (0.02 mol, marketed by Sigma Aldrich) instead of 1,3-propanediol. PLGA*4 was thus isolated with a yield of 88%.

[0289] PLGA*4 was analyzed by NMR (Bruker Avance III HD 400 spectrometer) MHz NMR equipped with a BroadBand Inverse (BBI) probe for ¹H NMR, and a Bruker AVANCE III 500 MHz NMR spectrometer equipped with a 5 mm ¹H / X BBO Helium cryoprobe and a Bruker Avance III 600 MHz NMR spectrometer for ¹³C NMR). The ¹H NMR spectrum is reproduced in [Fig. 4]. NMR analysis determined that PLGA*4 was terminated by 64% lactic acid and 36% glycolic acid, and that PLGA*4 had a hydroxyl group equivalent weight of 385 ± 6 g.eq.

[0290] Example 3: Synthesis of copolymers I (CP-1 to CP-11)

[0291] Poly(ε-caprolactone) diol (II) (50 g, marketed by Sigma Aldrich) and hexamethylene diisocyanate (>98%, 17 g, marketed by TCI Europe) were stirred at 80 °C to obtain a macrodiisocyanate, as described in Molecules, 2024, 29, 766. The macrodiisocyanate thus obtained was then introduced into a reactor. 17 mL of 1,4-dioxane (marketed by ACS Reagent and distilled over CaH2), as well as linear diol prepolymer IV (PLGA1) and / or Branched polyol prepolymer V (PLGA*2, PLGA*3, or PLGA*4), in the amounts described in Table 1 below, were also introduced into the reactor under a nitrogen atmosphere. The reaction mixture was stirred at 100 °C, and then 6 g of macrodiisocyanate and 0.5 wt% of tin(II) 2-ethylhexanoate were added relative to the macrodiisocyanate. The reaction mixture was stirred until the characteristic IR band of the isocyanate group disappeared (at 2300 cm⁻¹, measured using a ThermoScientific Nicolet iS50 FT-IR Flex Gold IR spectrometer equipped with a deuterated triglycine sulfate detector (DTGS)). At the end of the reaction, 40 mL of 1,4-dioxane was slowly added to control the viscosity of the mixture. The resulting copolymers were then purified by precipitation in a diethyl ether:EtOH (80:20) mixture.

[0292] [Tables 1] I IV mass (g) of IV V mass (g) of V Molar ratio of reactive functions V / IV Macrodiisocyanate conversion (%) CPI PLGA1 3.48 PLGA*2 1.2 25 / 75 90 CP2 PLGA1 3.31 PLGA*2 1.5 30 / 70 PLGA*2 3.38 PLGA PLGA*2 1.8 35 / 65 78 CP4 PLGA1 3.80 PLGA*3 0.2 5 / 95 86 CP5 PLGA1 2.92 PLGA*3 0.3 10 / 90 88 CP6 PLGA1 2.75 PLGA*3 0.5 PLGA1 85 / 71 3.22 PLGA*3 0.8 20 / 80 87 CPS PLGA1 3.01 PLGA*4 0.2 5 / 95 SI CP9 PLGA1 2.76 PLGA*4 0.3 10 / 90 80 CP10 PLGA1 3.34 PLGA*4 10.65 CPH / 76 invention) PLGA1 3.26 - - - 90

[0293] The physicochemical properties of these different copolymers were then tested and are detailed in Table 2. Since copolymers CP3, CP7, CP8, CP9, and CP10 are poorly soluble or insoluble, their number molecular weights were not determined. The number-average molar masses Mn and the mass-average molar masses Mw were determined using a SEC MALS detector (Agilent 1260 Infinity triple-detection SEC, Wyatt Optilab MALS detector, and Agilent differential refractometer). Separation was carried out using two PLgel and B LS columns (7.5 mm x 300 mm). THF was used as the eluent (at 30°C, with a flow rate of 1 mL / min). The refractive index (dn / dc) of the different reagents and copolymers obtained was measured as follows: five different concentrations (0.25 mg.mL 1; 0.5 mg.mL 1; 0.75 mg.mL 1; 1 mg.mL 1; 1.5 mg.mL 2 mg.mL1) of each product in THF were injected into the columns and the resulting RI signals were recorded as a function of concentration. The values ​​dn / . are detailed in Table 2, and were used for SEC-MALS analyses. The polydispersity index D is determined by the ratio Mw / Mn.

[0294] [Tables2] I IV V Molar ratio reactive functions V / IV Mn (g.moH) Mw (g.mol-1) B CPI PLGA1 PLGA*2 25 / 75 31700 67200 2.1 CP2 PLGA1 PLGA*2 30 / 70 40300 155200 3.9 CP3 PLGA1 PLGA*2 35 / 65 NA NA NA CP4 PLGA1 PLGA*3 5 / 95 72500 103100 1.4 CP5 PLGA1 PLGA*3 10 / 90 53700 127200 2.4 CP6 PLGA1 PLGA*3 15 / 85 67200 253700 3.8 CP7 PLGA1 PLGA*3 20 / 80 NA NA NA CP8 PLGA1 PLGA*4 5 / 95 NA NA NA CP9 PLGA1 PLGA*4 10 / 90 NA NA NA CP10 PLGA1 PLGA*4 15 / 85 NA NA NA CPH (excluding invention) PLGA1 - - 30600 56000 1.9

[0295] The thermal and mechanical properties of these copolymers were also tested by DSC and TGA analyses, and are detailed in Table 3 below.

[0296] Differential scanning calorimetry (DSC) analyses were performed using a NETZSCH DSC200F3 calorimeter (calibrated with indium, n-octanoate, n-octane, adamantane, biphenyl, tin, bismuth, and zinc standards; 40 mL min⁻¹ of nitrogen). Approximately 10 mg of sample were placed in perforated aluminum pans, and the thermal properties were recorded between -150 °C and 200 °C (20 °C min⁻¹ ramp*) to observe the glass transition temperature (Tg). Glass transition temperatures were measured on the second heating ramp to clear the polymer's thermal history.

[0297] Thermogravimetric analyses were performed on a Netzsch STA 449 Fl TGA apparatus under 50 mL / min of argon. Approximately 10 mg of sample were placed in an alumina crucible and heated from room temperature to 800 °C with a heating ramp of 20 °C / min*. Thermogravimetric analyses allow the thermal stability of the tested samples to be determined.

[0298] [Tables3] Te 5% (°C) Tf(°c) Ta (°C) CPI 266 52 17 CP2 231 52 27 CP3 249 44 24 CP4 238 49 29 CP5 244 52 45 CP6 227 60 22 CP7 230 50 NA CP8 230 59 20 CP9 265 54 37 CP10 241 53 48 CPU (excluding invention) 220 53 29

[0299] These analyses demonstrate that all the copolymers tested exhibit good thermal stability above 200 °C, with initial decomposition temperatures (Td, 5% – corresponding to the temperature at which 5% by mass of the copolymer degrades) occurring in the range of 220 to 266 °C, leaving only 10% and 5% of the residual weight upon heating to 400 °C and 600 °C, respectively. The excellent heat resistance demonstrated ensures good thermal stability at temperatures well above the melting temperatures Tf of the various synthesized copolymers. This provides a wide heat treatment window up to 160 °C above the melting temperature Tf, thus making these copolymers suitable candidates for hot pressing. All the copolymers obtained have fairly similar melting temperatures Tf, ranging between 44 and 59 °C.

[0300] Next, thermocompression (using a Carver 3690 press) was performed at 120 °C for 20 minutes under 1.2 tonnes of pressure for each copolymer. Each time, the resulting film was initially transparent, but it eventually became opaque over time due to recrystallization. All films were left at room temperature for 3 days before mechanical testing.

[0301] The mechanical performance of the copolymers was studied by tensile tests and is detailed in Table 4. These tests were carried out according to ASTM D1708-18.

[0302] The Young's modulus was measured and determined using an Instron apparatus equipped with 100 N load cells. The measurements were carried out at a speed of 5 mm.min*. All values ​​entered in Table 4 are an average of three measurements.

[0303] The tensile strength was determined at room temperature on at least three different samples approximately 2 mm wide and approximately 14 mm long and approximately 2 mm thick, using Instron 5900 equipment and at a strain rate of 10 mm.min 1

[0304] The elongation at break was determined using the tensile strength curve, and identified by the point from which the force drops.

[0305] [Tables4] I (film) Young's modulus (Ey) (MPa) tensile strength ( <j) (MPa) allongement à la rupture (e) (%) Ta (°C) Rd (%) Rf (%) Rr (%) CPI 61,03 ± 5,91 1,39 ± 0,78 15 ± 4 17 NA NA NA CP2 64,81 ± 5,78 1,48 ± 1,1 16 ± 6 27 NA NA NA CPS 8,58 ± 1,65 3,2 ± 0,31 740 ± 117 24 68 95 85 CP4 58,68 ± 18 5,73 ± 0,12 785 ± 28 29 53 96 92 CP5 96,30 ± 15,60 4,76 ± 1,55 21 ± 4 42 NA NA NA CP6 78,29 ± 14,2 8,27 ± 0,19 930 ± 32 22 45 82 90 CP7 75,17 ± 1,21 1,6 ± 0,66 20 ± 8 NA NA NA NA CP8 56,76± 2,01 7,66 ± 1,5 728 ± 125 20 49 81 88 CP9 90,26 ± 9,50 5,86 ± 0,44 266 ± 122 37 NA NA NA CP10 39,24 ± 1,78 1,54 ± 0,21 82 ± 6 48 NA NA NA CPH (hors invention) 71,84 ± 5,06 3,9 ± 1,26 755 ± 220 29 60 79 87

[0306] The copolymers obtained exhibited a wide range of stress-strain behavior, from hard (in the case of CPI, CP2, CP5, CP7, and CP10) to ductile (in the case of CP3, CP4, and CP8). Young's modulus increased with branching up to a threshold beyond which it decreased. Young's moduli, tensile strength, and elongation at break were found to be in the ranges of 5.86 to 96.3 MPa, 1.39 to 8.27 MPa, and 15 to 930%, respectively.

[0307] The shape memory of the different samples was also evaluated with a Mettler Toledo DMA 1 Star apparatus and STARe software, and the results are detailed in Table 4.

[0308] Example 4: Preparation of a porous solid

[0309] 3 g of copolymer I were dissolved in 9 mL of THF and 15 g of NaCl crystals (sieved at 100-300 µm) were added to the copolymer I solution. After vigorous stirring, the suspension was poured into a mold and rapidly frozen by immersion in liquid nitrogen before solvent evaporation at room temperature and reduced pressure overnight. The porous solid was washed with distilled water at room temperature until the NaCl crystals disappeared. The complete The disappearance of the crystals is determined by electron microscopy, by making different sections of the material.

[0310] The porosity P of the porous solid is determined using equation 1 above. The density was determined at room temperature by weighing a known volume of copolymer using a balance. The porosity values ​​detailed in Table 5 are the average of three determined porosities. The results are detailed in Table 5.

[0311] [Tables5] Porous solid SI S2 S4 S5 S6 SU (not part of the invention) Copolymer I used CPI CP2 CP4 CP5 CP6 CPU (not part of the invention) Porosity (%) 76 ± 5 80 ± 4 83 ± 1 78 ± 3 81 ± 1 74 ± 4 Mean pore diameter (pm) -■ 148 ± 40 - 110 ± 75 156 ± 35 Young's Modulus Ey (MPa) 0.142 ±0.03 0.533 ±0.20 0.217 ±0.03 0.316 ±0.11 0.152 ±0.06 0.134 ±0.09 E' (25°C) (MPa) 3.07 3.72 1.76 2.01 1.86 1.75 E' (37°C) (MPa) 0.81 1 0.42 0.6 0.77 0.55 Ta (°C) 35 33.7 34 33.1 35.4 33 Eflex (MPa) - 0.18 ± 0.02 - 0.24 ± 0.09 0.35 ± 0.05 a (MPa) - 0.24 ± 0.01 - - 0.25 ± 0.004 1.04 ± 0.03

[0312] The porous solids were analyzed by scanning electron microscopy (SEM) using a Phenom ProX Desktop microscope. For this purpose, cubic samples (2 to 3 mm on each side) were prepared, and the cross-section of the samples was coated with gold by spraying. Microscopic observations were performed at 10 kV. The mean pore diameters and the pore size distribution in the samples were determined using the hnageL program. Pore sizes are expressed as averages. The images obtained using the scanning electron microscope are reproduced in [Fig. 5]: SU (not part of the invention) in [Fig. 5].A, CP2 in [Fig. 5].B, and CP6 in [Fig. 5].C. The images show heterogeneous and interconnected porosity for the three copolymers.

[0313] The mechanical properties of the porous solids were also tested to determine the viscoelastic properties of the samples using a Mettler Toledo DMA 1 Star apparatus and STARe software at 1 Hz. The results obtained are detailed In Table 5, where E' represents the conservation modulus, E” the loss modulus, the loss factor tanô represents the ratio between E' and E”, and Ta represents the alpha transition temperature. The Young's modulus was determined as previously described in Example 3 for copolymers.

[0314] In general, the preservation modulus increases with the branching rate. At 37 °C, all samples have a preservation modulus acceptable for application as a medical implant (in a range from 0.1 MPa to 3 MPa).

[0315] The glass transition temperatures Tg are all measured between 33 °C and 35.4 °C.

[0316] The bending strength of the various porous solids was then tested using an Instron 5900 apparatus. The different samples were subjected to a three-point bending test at 100% bending. The bending modulus Eflex and the bending strength o are detailed in Table 5.

[0317] Example 5: Determination of degradation time

[0318] The degradation kinetics were studied in vitro under standard conditions using A phosphate buffer solution (PBS, pH 7.4) was used, and under accelerated conditions, an aqueous HCl solution (0.1 M, pH 1) was used at a constant temperature (37 °C) with continuous stirring (100 rpm). Porous solid samples were cut into cubes, weighed (mseCjto), and incubated in 1 mL of the medium solution. Samples were removed from the medium at various times, washed with distilled water, thoroughly dried, and then dried to a constant weight (msec>t). Degradation was monitored by determining the weight loss. The remaining mass was calculated using Equation 4 below.

[0319] [Math.4] 1--— -----I x 100 «sec.tO / (4)

[0320] The results obtained are detailed in Table 6 below.

[0321] [Tableauxô] Time (weeks) Percentage of remaining mass CP2 CP6 CPU 0 100 100 100 1 93 ±1 87 ±2 93 ±2 3 85 ±5 70 ±0 95 ±1 5 78 ±U 66 ±6 74 ±1 6 50 ±23 60 ±l 69 ±5

Claims

Demands

1. A porous solid (S) containing at least 90% by weight of a copolymer (I) relative to the total weight of the porous solid (S), said porous solid (S) having a porosity of 40% to 95% by volume, preferably 60% to 95% by volume, and an average pore diameter in the range of 25 microns to 500 microns, characterized in that the copolymer (I) is prepared in the following steps: 1) having at least one polyol (II), said polyol (II) being an aliphatic polyester polyol or a copolymer thereof, linear (II-L) or branched (II-R), 2) having at least one aliphatic or cyloaliphatic polyisocyanate (III), or a dimer or trimer thereof, linear (III-L) or branched (III-R), 3) having at least one prepolymer polyol (IV), linear (IV-L) or branched (IV-R), the prepolymer polyol (IV) being an aliphatic polyester polyol or an aliphatic polyester polyol copolymer,4) react at least one polyol (II) with at least one polyisocyanate (III) to obtain a macropolyisocyanate (V), 5) react the macropolyisocyanate (V) with at least one polyol prepolymer (IV), the molar percentage of reactive functions in the at least one branched polyol (II-R), the at least one branched polyisocyanate (III-R) and the at least one branched polyol prepolymer (IV-R) relative to the polyol (II), the polyisocyanate (III) and the polyol prepolymer (IV) being greater than 0% and less than or equal to 50%.

2. Porous solid (S) according to claim 1, wherein the molar percentage of reactive functions of branched polyol (II-R), branched polyisocyanate (III-R) and branched polyol prepolymer (IV-R) relative to polyol (II), polyisocyanate (III) and polyol prepolymer (IV) is in the range of 0.1 to 50%, preferably 0.2 to 45%, preferably 0.5 to 35% and even better 1 to 20%.

3. Porous solid according to claim 1 or 2, wherein the copolymer (I) is prepared according to the following steps: 1) having at least one polyol (II), said polyol (II) being an aliphatic polyester polyol or a copolymer of aliphatic polyester polyol, linear (II-L) or branched (II-R), 2) have at least one aliphatic or cyloaliphatic diisocyanate (III-L), or a dimer or trimer thereof, 3) have at least one linear diol prepolymer (IV-L), which is a linear aliphatic polyester diol or a linear aliphatic polyester diol copolymer, and have at least one branched polyol prepolymer (IV-R), which is a branched aliphatic polyester polyol, or a branched aliphatic polyester polyol copolymer, having at least three hydroxyl functions, 4) react at least one polyol (II) with at least one diisocyanate (III-L), to obtain a macropolyisocyanate (V), 5) react the macrodiisocyanate (V) with a mixture of at least one linear diol prepolymer (IV-L) and at least one branched polyol prepolymer (IV-R).

4. Porous solid (S) according to the preceding claim, wherein the molar ratio of reactive functions of the linear diol prepolymer (IV) to the reactive functions of the branched polyol prepolymer (V) in the mixture at step 5) ranges from 99:1 to 50:50, preferably from 98:2 to 60:40, and more preferably from 95:5 to 75:

35.

5. Porous solid (S) according to any one of the preceding claims, wherein, in step 2), the polyisocyanate (III) is a linear diisocyanate (III-La) of formula: ôÊ^^^côCHI-La) with M representing an alkylene, cyclic or acyclic (Cl-CIO) group, optionally interrupted by at least one urea (-NH-CO-NH-) group, and optionally substituted by one or more (C1-C6) alkyl groups, and / or one or more COOR1 groups with RI representing an (C1-C4) alkyl group, and / or one or more COOH groups.

6. Porous solid (S) according to any one of the preceding claims, wherein, in step 2), the polyisocyanate (III) is a linear diisocyanate (III-L) selected from: - (mL-2), (in-L-3), and A. ..o, T - NCO 0 no HOOC O NCO (III-L-4), and preferably diisocyanate (III) is ethyl ester diisocyanate of lysine (III-L-3).

7. Porous solid (S) according to any one of the preceding claims, wherein the polyol (II) is selected from poly(e-caprolactone) diol, linear or branched poly(lactic-co-glycolic) polyol or linear or branched poly(lactide-co-glycolide) polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers, preferably the initiator polyol (II) is poly(e-caprolactone) diol.

8. Porous solid (S) according to any one of the preceding claims, wherein the linear polyol prepolymer (IV-L) is selected from poly(e-caprolactone) diol, linear poly(lactic-co-glycolic) diol or linear poly(lactide-co-glycolide) polyol, polydioxanone diol, poly(lactic acid) diol or poly(lactide) diol, and their copolymers.

9. Porous solid (S) according to any one of the preceding claims, wherein the linear polyol prepolymer (IV-L) has the following formula: r%f%(IV-Ll), with: - A representing a group of the following formula, in which x and y are equal or different and independently represent an integer from 2 to 30, preferably from 10 to 30, more preferably from 12 to 20: wi ir îi (A), - L1 representing a linear (Cl-ClO) alkylene group optionally substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group; ethylene glycol; diethylene glycol; triethylene glycol; polyethylene glycol; or an (Cl-CIO) alkylene group, possibly substituted by an (C1-C6) alkyl group or an (C1-C6) alkyl ether group, and interrupted by a benzene.

10. Porous solid (S) according to the preceding claim, wherein L1 represents a linear (C1-C10) alkylene group, optionally substituted by an (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and preferably such that L1 represents (CH2)W with w representing an integer from 1 to 6, and preferably 3.

11. Porous solid (S) according to any one of the preceding claims, wherein the branched polyol pre-polymer (IV-R) has the following formula: Â.^%(V4<-1), with: - A representing a group of the following formula, in which x and y are equal or different and independently represent an integer from 2 to 30, preferably from 10 to 30, more preferably from 12 to 20: î ii in r â J? 6* ■ - L2 representing a (C1-C10) alkylene group, linear or branched, or cycloalkylene of which one or more CH2s may be replaced by O, substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1, possibly substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group, and possibly interrupted by a benzene; or a benzene group substituted by at least one (CH2)Z-OA group with z being an integer greater than or equal to 1 and possibly substituted by a (C1-C6) alkyl group or by an (C1-C6) alkyl ether group.

12. Porous solid (S) according to the preceding claim, wherein L2 is substituted by one, two, three, four, five or six (CH2)Z-OA groups with z being an integer greater than or equal to 1.

13. Porous solid (S) according to any one of the preceding claims, wherein the linear polyol prepolymer (IV-L) and the branched polyol prepolymer (IV-R) each have a number-average molar mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol.

14. Porous solid (S) according to any one of the preceding claims, wherein the macropolyisocyanate (V) obtained at step 4) has an average molar number mass ranging from 100 to 10000 g / mol, preferably from 1000 to 5000 g / mol.

15. Porous solid (S) according to any one of the preceding claims having a bending strength in the range of 0.1 MPa to 5 MPa.

16. Porous solid (S) according to any one of the preceding claims, characterized in that it is biocompatible and bioresorbable.

17. A method for preparing a porous solid (S) according to any one of the preceding claims comprising solubilizing the copolymer (I) in a solvent to obtain a solution of copolymer (I) followed by evaporating said solvent.

18. A method for preparing a porous solid (S) according to the preceding claim, further comprising suspending a porous agent in the copolymer solution (I).

19. A method for preparing a porous solid (S) according to claim 17 or 18 comprising cooling the copolymer solution (I) before evaporating the solvent.

20. A method for preparing a porous solid (S) according to any one of claims 1 to 16 comprising heating the copolymer (I) to a temperature greater than or equal to its melting temperature and then cooling it.

21. Medical implant material consisting of porous solid (S) according to any one of claims 1 to 16, or obtained according to the process according to any one of claims 17 to 20, and collagen.

22. Medical implant material according to the preceding claim, wherein the collagen is recombinant human collagen.

23. Medical implant material according to claim 21 or 22, wherein the porous solid (S) is covered by collagen.

24. Medical implant material according to the preceding claim, wherein the collagen covers the periphery of the porous solid (S), and the walls of the pores of the porous solid (S).

25. Medical implant material according to any one of claims 21 to 24, characterized in that it is biocompatible and bioresorbable.

26. Medical implant material according to any one of claims 21 to 25, having an in vivo degradation time of less than one year.

27. ​​A method for preparing a medical implant material according to any one of claims 21 to 26, comprising immersing the porous solid (S) according to any one of claims 1 to 16 or obtained according to the method according to any one of claims 17 to 20 in collagen, or injecting or vaporizing collagen onto it.

28. Medical implant made of medical implant material according to any one of claims 21 to 26, or of medical implant material obtained in accordance with the process according to the preceding claim.

29. Medical implant according to the preceding claim, said implant being a meniscal implant, a condylar cartilage implant, a tibial cartilage implant, a hip cartilage implant, a shoulder cartilage implant, or an ankle cartilage implant.

30. Use of the porous solid (S) according to any one of claims 1 to 16 or of the porous solid (S) obtained according to the process according to any one of claims 17 to 20, or of the medical implant material according to any one of claims 21 to 26 or of the medical implant material obtained according to the process according to claim 27, for the production of a medical implant.

31. Kit comprising the porous solid (S) according to any one of claims 1 to 16 or the porous solid (S) obtained according to the process according to any one of claims 17 to 20, or comprising the medical implant material according to any one of claims 21 to 26 or the medical implant material obtained according to the process according to claim 27.

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