An artificial meniscus and its preparation method

Abstract

The present invention belongs to the field of medical composite materials. The present invention relates to an artificial meniscus and a preparation method thereof. The method includes: preparing a mold for making a disc-shaped artificial meniscus; arranging a functional fiber fabric on the inner side of the mold; adding a modified polyurethane-based material solution into the mold, removing bubbles, and standing to obtain a formed product I; placing the formed product I in a glutaraldehyde solution for 5-10 h to obtain a formed product II; placing the formed product II in a calcium bromide solution for 2-5 h to obtain a target product. The artificial meniscus effectively solves the problems of poor mechanical properties and cartilage contusion existing in the current existing artificial menisci.

Description

Technical Field

[0001] The present invention relates to an artificial meniscus and a preparation method thereof. The present invention belongs to the field of biocomposites. Background Art

[0002] The meniscus is a crescent-shaped fibrocartilage tissue, which consists of water, extracellular matrix and meniscus cells. The meniscus exists in the hinge joints of the human knee, wrist and jaw. The knee meniscus is located between the femur and the tibial plateau and plays an important role. It bears various loads in both daily life and sports activities, such as compression, rotation, stretching, shearing, etc. The functions of the meniscus mainly include: load-bearing, improving the adaptability of the tibiofemoral joint, maintaining the stability of the knee joint, buffering stress and shock, lubricating the joint, increasing the joint contact area, etc. When the meniscus is bruised, the normal function of the knee joint will be greatly attenuated, the burden on the knee joint will be serious, especially during strenuous sports activities, and the meniscus cannot regenerate. Therefore, it is urgent to develop an artificial meniscus substitute to provide the corresponding functions of the excised natural meniscus, thereby slowing down or even avoiding the wear of articular cartilage.

[0003] An ideal meniscus substitute should have geometric characteristics, anisotropic mechanical properties, excellent biocompatibility and long-term in vivo stability similar to those of the natural meniscus. For this reason, scientific researchers have successively developed various types of meniscus substitutes, including polytetrafluoroethylene, polyester, porous polyurethane, polyvinyl alcohol hydrogel, polycarbonate polyurethane, etc. However, the above-mentioned meniscus substitutes all have some deficiencies. For example, polytetrafluoroethylene materials have low strength and poor wear resistance, are prone to deformation and wear after implantation, resulting in the deposition of debris in the joint cavity and the formation of synovitis, damaging articular cartilage; polyester also has synovitis and wear of articular cartilage; porous polyurethane also damages articular cartilage; polyvinyl alcohol hydrogel has poor mechanical properties; polycarbonate polyurethane has a large friction coefficient and damages cartilage tissue, etc.

[0004] Therefore, considering the above scientific research status and the urgent need for artificial meniscus, it is of great significance to develop an artificial meniscus material with high mechanical properties, low wear and high biocompatibility. Summary of the Invention

[0005] The purpose of the present invention is to provide an artificial meniscus and a preparation method thereof for the problems of poor mechanical properties and cartilage contusion of the artificial meniscus in the prior art. The present invention prepares an artificial meniscus material through molecular design and prepares it through structural optimization design. The technical solution adopted by the present invention to solve its technical problems is:

[0006] The present invention provides a preparation method of a modified polyurethane-based material, comprising the following steps:

[0007] S11. Conduct an ester exchange reaction between hydroxymethyldioxolane and dimethyl carbonate to obtain intermediate product 1I;

[0008] S12. Conduct a ring-opening reaction between intermediate product 1I and a diamine to obtain intermediate product 1II;

[0009] S13. Blend intermediate product 1II with a bio-macromolecule containing amino groups to obtain the target product, i.e., the modified polyurethane-based material.

[0010] Further, the molar ratio of hydroxymethyldioxolane to dimethyl carbonate is 2:1.

[0011] Further, the molar ratio of intermediate product 1I to the diamine is 1:1; and

[0012] The diamine is added in a molar ratio of 2.0 - 3.0:7.0 - 8.0 of macromolecular diamine to small molecular diamine.

[0013] Further, the macromolecular diamine is polyethylene glycol diamine or / and polyether diamine; and

[0014] The small molecular diamine is a mixture of aliphatic diamine and aromatic diamine.

[0015] Further, the dosage ratio of intermediate product 1II to the bio-macromolecule containing amino groups is 7.5 - 9.5 g:0.5 - 2.5 g; and

[0016] The bio-macromolecule containing amino groups includes gelatin and chitosan.

[0017] The present invention also provides a modified polyurethane-based material prepared by the above preparation method.

[0018] Another object of the present invention is to provide a preparation method of a functional fiber fabric, comprising the following steps:

[0019] S21. Conduct a condensation reaction between a dicarboxylic acid and a polyamine A to obtain intermediate product 2I;

[0020] S22. Conduct a ring-opening reaction between intermediate product 1I and a polyamine B to obtain intermediate product 2II;

[0021] S23. Conduct a polycondensation reaction between intermediate product 2I and intermediate product 2II to obtain intermediate product 2III;

[0022] S24. Conduct a free radical polymerization of acrylamide and zwitterions to obtain intermediate product 2IV;

[0023] S25. Blend intermediate product 2III and intermediate product 2IV, and conduct spinning and carding to obtain the functional fiber fabric.

[0024] Furthermore, the molar ratio of the dibasic acid to the polyamine A is 0.5 - 2.0:1.0; and,

[0025] The dibasic acid includes terephthalic acid;

[0026] The polyamine A is added with a diamine and a triamine in a molar ratio of 0.8 - 1.0:0 - 0.2;

[0027] The diamine is a water-soluble diamine; including polyether diamine;

[0028] The triamine includes melamine.

[0029] Furthermore, the molar ratio of the intermediate product 1I to the polyamine B is 0.5 - 2.0:1.0; and,

[0030] The polyamine A is added with a diamine and a triamine in a molar ratio of 0.8 - 1.0:0 - 0.2;

[0031] The diamine is a water-soluble diamine; including polyether diamine;

[0032] The triamine includes melamine.

[0033] Furthermore, the intermediate product 2I and the intermediate product 2II are added in a molar ratio of 1.0:1.0.

[0034] Furthermore, the molar ratio of acrylamide to the zwitterion is 0.7 - 0.9:0.1 - 0.3; and,

[0035] The zwitterion is phosphorylcholine or betaine.

[0036] Furthermore, the dosage ratio of the intermediate product 2III to the intermediate product 2IV is 7.0 - 9.0 g:1.0 - 3.0 g.

[0037] The present invention also provides a functional fiber fabric prepared by the above preparation method.

[0038] Another object of the present invention is to provide a preparation method of an artificial meniscus, including:

[0039] S31, preparing a mold for making a disc-shaped artificial meniscus;

[0040] S32, arranging a functional fiber fabric on the inner side of the mold;

[0041] S33, adding a modified polyurethane-based material solution into the mold, removing bubbles, and standing to obtain a molded product I;

[0042] Wherein, the outer end of the artificial meniscus is connected to the functional fiber fabric;

[0043] S34. Place the formed product I in a glutaraldehyde solution for 5 - 10 h to obtain formed product II;

[0044] S35. Place the formed product II in a calcium bromide solution for 2 - 5 h to obtain the target product, i.e., the artificial meniscus.

[0045] Furthermore, the preparation method of the glutaraldehyde solution is as follows:

[0046] Add an aqueous glutaraldehyde solution to acetonitrile, add a solid water desiccant, seal and dry for 0.5 h, then filter to obtain a glutaraldehyde - acetonitrile solution;

[0047] The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and the solid water desiccant is 10 - 20 mL: 480 - 490 mL: 100 g;

[0048] The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

[0049] Furthermore, the concentration of the calcium bromide is 0.01 - 0.1 g / mL.

[0050] The present invention also provides an artificial meniscus prepared by the above - mentioned preparation method.

[0051] Advantages of the present invention:

[0052] (1) The present invention provides an artificial meniscus composed of an internal matrix material and an external functional fiber fabric. The internal matrix material is mainly a non - isocyanate polyurethane structure and is a modified polyurethane - based material blended with amino - containing biological macromolecules. First, non - isocyanate polyurethane avoids using toxic isocyanate structures and has stronger molecular designability; at the same time, there are a large number of hydroxyl groups in the macromolecular chain, which can form intramolecular hydrogen - bond rings or intermolecular hydrogen bonds, effectively improving the mechanical properties; second, the hydroxyl groups that do not participate in intramolecular or intermolecular hydrogen - bond pairing can form hydrogen bonds with biological macromolecules, improving compatibility; third, non - isocyanate polyurethane can be designed for molecular functionalization on the amine source, and the use of macromolecular water - soluble diamine and small - molecule diamine in combination can effectively improve the hydrophilicity and mechanical properties of the matrix; fourth, amino - containing biological macromolecules provide excellent biocompatibility, are conducive to cell proliferation and differentiation, and can participate in chemical reactions with the external functional fiber fabric.

[0053] (2) The present invention provides an artificial meniscus, which is composed of an internal matrix material and an external functional fiber fabric. The external functional fiber fabric is mainly prepared by block copolymerization of a non-isocyanate polyurethane structure and a polyamide structure, and is prepared by mixing and spinning with a polyamide / zwitterionic copolymer. First, polyamide fibers have excellent mechanical properties and chemical corrosion resistance, etc., which can effectively ensure the dimensional stability of the material in a complex environment; second, the non-isocyanate polyurethane structure in the functional fiber fabric has excellent compatibility with the internal matrix material and can form hydrogen bonds, reducing relative slippage during the stress deformation process; third, the polyamide / zwitterionic copolymer component provides hydrophilicity for the functional fiber fabric, effectively improving the lubrication performance between the artificial meniscus and cartilage tissue, reducing wear and lessening contusion; fourth, the ammonium salt, phosphate or sulfonate in the zwitterionic structure is similar to the cell composition structure, which can promote joint lubrication, reduce inflammation and protect cartilage.

[0054] (3) The present invention provides a method for preparing an artificial meniscus, which is prepared by crosslinking an internal matrix material and an external functional fiber fabric in a mold with glutaraldehyde and calcium bromide. First, glutaraldehyde can carry out an aldehyde-amine condensation crosslinking reaction with the residual amino groups in the matrix material and the functional fiber fabric, improving the mechanical properties of the matrix, effectively reducing the relative slippage between the matrix material and the functional fiber fabric, and further improving the mechanical properties; second, the calcium ions in calcium bromide coordinate with groups such as amino groups, carbonyl groups, phosphate groups (or sulfonate groups), improving the mechanical properties; third, the bromide ions in calcium bromide have the function of inducing the regeneration and differentiation of chondrocytes, and can effectively play a role in promoting cartilage repair; and the bromide ions form an ammonium salt structure with ammonium ions, having a slow-release and long-acting effect. Specific embodiments

[0055] The present invention will be described in detail below with reference to the embodiments. However, it should be understood that the following embodiments are only illustrative examples of the implementation modes of the present invention, rather than limiting the scope of the present invention.

[0056] The object of the present invention is to develop an artificial meniscus to solve the problems of poor mechanical properties and cartilage contusion existing in the existing artificial meniscus.

[0057] The implementation idea is as follows: Taking the main physical properties of natural meniscus (tensile strength 13.25 MPa, friction coefficient 0.14, relative cell survival rate 100%) as the goal, using polyurethane material as the main body, through chemical modification and physical structure design, to improve the mechanical properties of the material and the problem of bruised cartilage. First, design the overall structure with modified polyurethane as the matrix material; and design a "mesh cover" for this matrix material, then form an integral body of the matrix material and the "mesh cover" to solve the problem of insufficient mechanical properties; at the same time, carry out chemical modification on the matrix material and the "mesh cover" to solve the problems of poor mechanical properties and bruised cartilage; in addition, for bruised cartilage, on the one hand, reduce the friction coefficient; on the other hand, solve it by promoting cartilage proliferation compensation.

[0058] For chemical modification, the matrix is specifically: taking polycarbonate polyurethane as the main matrix, using the preparation method of non-isocyanate polyurethane to avoid using toxic isocyanate monomers, and at the same time, the polyurethane structure prepared by this method has more excellent mechanical properties; blending it with amino-containing biopolymers can improve its hydrophilicity and is beneficial to biocompatibility; the external "mesh cover" is specifically: prepared by copolymerizing polyamide and polyurethane, which not only improves the compatibility with the matrix but also provides the mechanical strength of the fiber structure; and blending it with polyamide / zwitterionic copolymer to enhance water solubility; in addition, the structure of the zwitterion can form new ions with calcium bromide ions, which has the effect of promoting cartilage proliferation. Integrate the two materials according to the structural design through an "integrated" process, place them in an aldehyde solution for cross-linking to form an integral body, and place them in a calcium bromide solution to form a new function.

[0059] The theoretical basis for realization is as follows: For the modified polyurethane material, first carry out the transesterification reaction of hydroxymethyldioxolane and dimethyl carbonate, and then carry out ring-opening with polyamine to prepare non-isocyanate polyurethane material, and blend it with amino-containing biopolymers to obtain it. For the functional fiber fabric ("mesh cover"), prepare polyamide and polyurethane prepolymers respectively, then carry out condensation reaction to prepare, and then prepare polyamide / zwitterionic copolymer through free radical polymerization, and finally blend them to obtain it. For "integration", place the two materials in an aldehyde solution according to the structural design for aldehyde-amine condensation reaction; take it out, place it in a calcium bromide solution for ion exchange to obtain the target product, an artificial meniscus. The embodiments of the present invention are as follows:

[0060] The embodiment of the present invention provides a preparation method of a modified polyurethane-based material, including the following steps:

[0061] S11, under N2 protection, mix hydroxymethyldioxolane and dimethyl carbonate, add a catalyst, stir, heat up to 160 - 180 °C, react for 1 - 3 h, and carry out vacuum distillation to obtain intermediate product 1I.

[0062] The molar ratio of the hydroxymethyldioxolane and dimethyl carbonate is 2:1.

[0063] The dosage of the catalyst is 0.1 - 0.2 wt% of the total mass of the reactants;

[0064] The catalyst can be titanium glycolate, tetrabutyl titanate, tetraisopropyl titanate, etc.; and tetrabutyl titanate is preferred.

[0065] S12, under N2 protection, add the intermediate 1I and the diamine to N,N-dimethylformamide A, stir, heat up to 80 - 100 °C and react for 6 - 8 h, then continue to heat up to 100 - 120 °C and react for 1 - 2 h; after the reaction is completed, perform vacuum distillation to obtain the intermediate 1II.

[0066] The dosage ratio of the intermediate 1I, the diamine, and N,N-dimethylformamide A is 1 mol:1 mol:400 mL;

[0067] The diamine is added in a molar ratio of 2.0 - 3.0:7.0 - 8.0 of the macromolecular diamine to the small molecular diamine.

[0068] The macromolecular diamine is polyethylene glycol diamine or / and polyether diamine;

[0069] The molecular weight of the polyethylene glycol diamine is 300 - 1000, specifically it can be 300, 400, 600, 1000, etc., or it can be customized according to requirements.

[0070] The molecular weight of the polyether diamine is 300 - 1000, specifically it can be 300, 500, 600, 1000, etc., or it can be customized according to requirements.

[0071] The small molecular diamine is a mixture of an aliphatic diamine and an aromatic diamine in a molar ratio of 0.5 - 0.7:0.3 - 0.5;

[0072] The aliphatic diamine can be isophorone diamine, triethylenetetramine, tetraethylenepentamine, cyclohexanediamine, ethylenediamine, propylenediamine, tetramethylenediamine, pentamethylenediamine, hexamethylenediamine, 1,12-diaminododecane, etc.; and triethylenetetramine is preferred.

[0073] The aromatic diamine can be p-phenylenediamine, o-phenylenediamine, m-phenylenediamine, etc.; and p-phenylenediamine is preferred.

[0074] S13, add the intermediate 1II and the amino-containing biological macromolecule to hot N,N-dimethylformamide B, continuously stir at 40 - 60 °C for 3 - 5 h, and perform vacuum distillation to obtain the target product, i.e., the modified polyurethane-based material.

[0075] The dosage ratio of the intermediate 1II, the amino group-containing biological macromolecule, and N,N-dimethylformamide B is 7.5-9.5 g: 0.5-2.5 g: 100 mL.

[0076] The amino group-containing biological macromolecule includes gelatin and chitosan;

[0077] The gelatin is commercially available animal-derived gelatin;

[0078] The deacetylation degree of the chitosan is ≥95%.

[0079] In the present invention, the preparation method of the modified polyurethane-based material adopts a non-isocyanate polyurethane synthesis method. The hydroxyl groups generated by ring-opening polymerization can form intramolecular or intermolecular hydrogen bonds, and the mechanical properties are more excellent; after blending it with gelatin or chitosan, the hydrophilicity and biocompatibility can be improved, and it can undergo a cross-linking reaction with glutaraldehyde, enabling it to have the ability to resist complex forces as a whole.

[0080] The embodiment of the present invention also provides a preparation method of a functional fiber fabric, including the following steps:

[0081] S21, Add dibasic acid, polyamine A, and deionized water A to the reaction kettle, protect with N2, heat up to 240-260 °C, 1.5-1.7 MPa, and react for 2-4 h; reduce to normal pressure and continue to react for 2-3 h; after the reaction is completed, evacuate for 1 h to obtain intermediate 2I.

[0082] The dosage ratio of the dibasic acid, polyamine A, and deionized water A is 0.5-2.0 mol: 1.0 mol: 300 mL;

[0083] The dibasic acid includes terephthalic acid; it can also be glutaric acid, adipic acid, etc.

[0084] The polyamine A is added in a molar ratio of 0.8-1.0: 0-0.2 of diamine to triamine;

[0085] The diamine is a water-soluble diamine; including polyether diamine;

[0086] The triamine includes melamine; it can be a mixture of melamine and 1,2,3-propanetriamine in a molar ratio of 2.0-4.0: 1.0 or a mixture of melamine and 1,3,5-triphenylamine in a molar ratio of 1.0-2.0: 1.0.

[0087] S22, Protect with N2, add intermediate 1I and polyamine B to N,N-dimethylformamide C, stir, heat up to 80-100 °C and react for 6-8 h, then continue to heat up to 100-120 °C and react for 1-2 h; after the reaction is completed, carry out vacuum distillation to obtain intermediate 2II.

[0088] The dosage ratio of the intermediate 1I, polyamine B, and N,N-dimethylformamide C is 0.5 - 2.0 mol : 1.0 mol : 500 mL;

[0089] The polyamine B is added in a molar ratio of 0.8 - 1.0:0 - 0.2 of diamine to triamine;

[0090] The diamine is a water-soluble diamine; including polyether diamine;

[0091] The triamine includes melamine; it can be a mixture of melamine and 1,2,3-propanetriamine in a molar ratio of 2.0 - 4.0:1.0 or a mixture of melamine and 1,3,5-triphenylamine in a molar ratio of 1.0 - 2.0:1.0.

[0092] S23, subject the intermediate 2I and intermediate 2II to a polycondensation reaction to obtain intermediate 2III.

[0093] The intermediate 2I and intermediate 2II are added in a molar ratio of 1.0:1.0.

[0094] The reaction process used in the S23 polycondensation reaction depends on the end-capping groups in S21 and S22: If S21 is a carboxyl-end capped structure and S22 is an amino-end capped structure, then the polycondensation reaction of S23 is the same as S21, which is a polyamide synthesis process step; conversely, if S21 is an amino-end capped structure and S22 is an intermediate 1I-end capped structure; then the polycondensation reaction of S23 is the same as S22, which is a polyurethane synthesis process step.

[0095] S24, add acrylamide, zwitterion, and photoinitiator to N,N-dimethylformamide D, irradiate under a UV lamp for 10 - 50 min, then remove the UV lamp, perform vacuum distillation, add methanol to the concentrate to produce precipitation, filter, collect the precipitate, and vacuum dry it at 60 °C for 8 h to obtain intermediate 2IV.

[0096] The dosage ratio of acrylamide, zwitterion, and N,N-dimethylformamide D is 0.7 - 0.9 mol : 0.1 - 0.3 mol : 500 mL;

[0097] The zwitterion is phosphorylcholine or betaine;

[0098] The phosphorylcholine can be 2-methacryloyloxyethyl phosphorylcholine, etc.;

[0099] The betaine can be methacryloylethyl sulfobetaine, acryloylethyl sulfobetaine, or 4-[[2-(methacryloyloxy)ethyl]dimethylammonio]butane-1-sulfonate, etc.

[0100] The dosage of the photoinitiator is 1 - 5 wt% of the total mass of the reactants;

[0101] The photoinitiator is a commonly used photoinitiator, which can be photoinitiator 1173, photoinitiator 184, photoinitiator 2959, photoinitiator 369, photoinitiator TPO, etc.; and in the following examples of the present invention, the photoinitiator is photoinitiator 1173.

[0102] The UV lamp intensity is 200 - 600 mW / cm 2 ; specifically, it can be 200 mW / cm 2 , 300 mW / cm 2 , 400 mW / cm 2 , 500 mW / cm 2 , 600 mW / cm 2 ; and in the following examples of the present invention, the UV lamp intensity is 400 mW / cm 2 .

[0103] S25. Dissolve intermediate 2III and intermediate 2IV in deionized water B, stir for 2 - 3 h, then defoam. Under stirring conditions, prepare by passing through a spinning device, carding by a carding machine, and using the needle punching method, and then cut, inspect, and disinfect to obtain the functional fiber fabric.

[0104] The dosage ratio of intermediate 2III, intermediate 2IV, and deionized water B is 7.0 - 9.0 g : 1.0 - 3.0 g : 1000 mL.

[0105] In the present invention, the functional fiber fabric has a pendant amino structure, so at least one of polyamine A and polyamine B has a tertiary amine structure.

[0106] In the present invention, the functional fiber fabric is mainly composed of a polyamide / polyurethane block structure and supplemented by a polyamide / zwitterionic copolymer. First, in the polyamide / polyurethane structure, polyamide has excellent mechanical strength, and polyurethane has excellent compatibility with the matrix; at the same time, combining the dimensional stability of polyamide with the flexibility of polyurethane, with complementary advantages, it can have both the mechanical strength of polyamide, dimensional stability, and the flexibility of polyurethane; on the other hand, the polyamide / zwitterionic copolymer has excellent water solubility, and can adsorb calcium ions through coordination and electrostatic interaction, and can adsorb bromide ions through electrostatic interaction, endowing the function of promoting cartilage proliferation. This functional fiber fabric has the advantages of reducing the relative slip between the fiber and the matrix, strong fiber dimensional stability, and excellent corrosion resistance; at the same time, it has functions such as adsorbing bromide ions. In addition, the pendant amino group in this functional fiber fabric can be used as a reaction structure anchor to further provide mechanical properties; at the same time, as a "protective mesh cover" for the matrix material, it can effectively protect the dimensional stability of the product.

[0107] An embodiment of the present invention also provides a method for preparing an artificial meniscus, including:

[0108] S31, preparing a mold for making a disc-shaped artificial meniscus.

[0109] S32, arranging a functional fiber fabric inside the mold.

[0110] S33, adding a modified polyurethane-based material solution into the mold, removing bubbles, and standing still to obtain Forming I.

[0111] Wherein, the outer end of the artificial meniscus is connected to the functional fiber fabric;

[0112] In the following embodiments of the present invention, the modified polyurethane-based material solution is a mixture of a modified polyurethane-based material and N,N-dimethylformamide E in a dosage ratio of 10 g: 100 mL.

[0113] S34, placing Forming I in a glutaraldehyde solution for 5 - 10 h to obtain Forming II.

[0114] The preparation method of the glutaraldehyde solution is as follows:

[0115] Adding an aqueous glutaraldehyde solution into acetonitrile, adding a solid water desiccant, sealing and drying for 0.5 h, and then filtering to obtain a glutaraldehyde acetonitrile solution.

[0116] The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and the solid water desiccant is 10 - 20 mL: 480 - 490 mL: 100 g;

[0117] The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

[0118] S35, placing Forming II in a calcium bromide solution for 2 - 5 h, placing the product in a dialysis bag, dialyzing with deionized water for 3 d, changing the dialysis fluid once a day, and freeze-drying to obtain the target product, i.e., the artificial meniscus.

[0119] The concentration of the calcium bromide is 0.01 - 0.1 g / mL.

[0120] In the following embodiments of the present invention, for the solutions described, unless otherwise specified, the solvent is water.

[0121] In the present invention, the artificial meniscus uses a self-made modified polyurethane material as the matrix material and a functional fiber fabric as the external "constraint" material. After being impregnated with glutaraldehyde, the amino-containing biological macromolecules in the matrix material and the pendant amino groups of the external "constraint" material can both undergo aldehyde-amine condensation reactions, firmly wrapping the external "constraint" material around the matrix material to form an integral material. At the same time, after being impregnated with a calcium bromide solution, bromide ions, calcium ions, ammonium ions, and phosphate ions in the zwitterions are affected by electrostatic force and ring tension. At the same time, the ionic radii of bromide ions and calcium ions are smaller than those of ammonium ions and phosphate ion clusters. Eventually, it is easier for bromide ions to combine with ammonium ions to form positive and negative ions, and calcium ions combine with phosphate ions, improving the sustained release effect of bromide ions, promoting the proliferation and differentiation of chondrocytes, compensating for worn cartilage, and increasing the service life.

[0122] To further understand the present invention, the following specifically describes an artificial meniscus provided by the present invention in combination with specific embodiments. The protection scope of the present invention is not limited by the following embodiments.

[0123] A preparation method of a modified polyurethane-based material includes the following steps:

[0124] S11, under N2 protection, mix hydroxymethyldioxolane and dimethyl carbonate, then add tetrabutyl titanate, stir, heat up to 170 °C, react for 1.5 h, and perform vacuum distillation to obtain intermediate product 1I.

[0125] The molar ratio of hydroxymethyldioxolane to dimethyl carbonate is 2:1.

[0126] The dosage of tetrabutyl titanate is 0.15 wt% of the total mass of the reactants.

[0127] Its infrared data is as follows: 3414 cm -1 : -OH does not exist; 1801 cm -1 : cyclic ester -C=O exists; 1732cm -1 : ester -C=O exists; 1255 cm -1 、1110cm -1 : -C-O-C- exists.

[0128] S12, under N2 protection, add intermediate product 1I and diamine to N,N-dimethylformamide A, stir, heat up to 90 °C and react for 6.5 h, then continue to heat up to 110 °C and react for 1.5 h; after the reaction is completed, perform vacuum distillation to obtain intermediate product 1II.

[0129] The dosage ratio of intermediate product 1I, diamine, and N,N-dimethylformamide A is 1 mol: 1 mol: 400 mL;

[0130] The diamine is added in a molar ratio of 2.5:7.5 of macromolecular diamine to small molecular diamine.

[0131] The macromolecular diamine is polyethylene glycol diamine with a molecular weight of 400.

[0132] The small molecular diamine is a mixture of triethylenetetramine and p-phenylenediamine in a molar ratio of 0.6:0.4.

[0133] Its infrared data is as follows: 3407 cm -1 : -OH is present; 3317 cm -1 : -NH- is present (single peak); 1801 cm -1 : cyclic ester -C=O is absent; 1725 - 1735 cm -1 : ester -C=O is present; 1255 cm -1 、1110 cm -1 : -C-O-C- is present.

[0134] S13. Add intermediate product 1II and gelatin to hot N,N-dimethylformamide B, continuously stir at 50 °C for 4 h, and perform vacuum distillation to obtain the target product, i.e., the modified polyurethane-based material.

[0135] The dosage ratio of the intermediate product 1II, gelatin, and N,N-dimethylformamide B is 8.5 g:1.5 g:100 mL.

[0136] Its infrared data is as follows: 3407 cm -1 : -OH is present; 3322 cm -1 : -NH- is present and enhanced; 1725 - 1735 cm -1 : ester -C=O is present; 1255 cm -1 、1110 cm -1 : -C-O-C- is present.

[0137] A preparation method of a functional fiber fabric includes the following steps:

[0138] S21. Add phthalic acid, polyamine A, and deionized water A to a reaction kettle, protect with N2, heat to 250 °C under 1.6 MPa, react for 3 h; reduce to normal pressure and continue to react for 2.5 h; after the reaction ends, perform vacuum pumping for 1 h to obtain intermediate product 2I.

[0139] The dosage ratio of the phthalic acid, polyamine A, and deionized water A is 2.0 mol:1.0 mol:300 mL.

[0140] The polyamine A is added in a molar ratio of 0.9:0.1 of diamine to triamine;

[0141] The diamine is polyether diamine with a molecular weight of 500;

[0142] The triamine is a mixture of melamine and 1,2,3-propanetriamine at a molar ratio of 3.0:1.0.

[0143] Its infrared data is as follows: 3322 cm -1 : -NH- present; 3017 cm -1 : -C-H benzene ring present; 1664cm -1 : amide -C=O present; 3402cm -1 : -OH present and weakened; 1764cm -1 : carboxylic acid -C=O present and weakened.

[0144] Under S22, N2 protection, the intermediate 1I and polyamine B are added to N,N-dimethylformamide C, stirred, heated to 90 °C and reacted for 6.5 h, then further heated to 110 °C and reacted for 1.5 h; after the reaction, vacuum distillation is carried out to obtain the intermediate 2II.

[0145] The dosage ratio of the intermediate 1I, polyamine B, and N,N-dimethylformamide C is 0.5 mol: 1.0 mol: 500 mL;

[0146] The polyamine B is added in a molar ratio of 0.9:0.1 of diamine to triamine;

[0147] The diamine is polyether diamine with a molecular weight of 500;

[0148] The triamine is a mixture of melamine and 1,2,3-propanetriamine at a molar ratio of 3.0:1.0.

[0149] Its infrared data is as follows: 3407 cm -1 : -OH present; 3318 cm -1 : -NH- present; 1801 cm -1 : ring -C=O absent; 1725 - 1735cm -1 : -C=O present; 1255 cm -1 、1110cm -1 : -C-O-C- present.

[0150] Under S23, the intermediate 2I, intermediate 2II, and deionized water are added to the reaction kettle, under N2 protection, heated to 255 °C, 1.6 MPa, and reacted for 3 h; cooled to atmospheric pressure and continued to react for 2.5 h; after the reaction, evacuated for 1 h to obtain the intermediate 2III.

[0151] The dosage ratio of the intermediate 2I, intermediate 2II, and deionized water is added as 1.0 mol: 1.0 mol: 300 mL.

[0152] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1764 cm -1 : carboxylic acid -C=O does not exist; 1725 - 1735 cm -1 : ester -C=O exists; 1664 cm -1 : amide -C=O exists; 1255 cm -1 , 1110 cm -1 : -C-O-C- exists.

[0153] S24. Add acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and photoinitiator 1173 to N,N-dimethylformamide D, irradiate under a UV lamp for 30 min, then remove the UV lamp, perform vacuum distillation, add methanol to the concentrate to produce a precipitate, filter, take the precipitate, and dry it under vacuum at 60 °C for 8 h to obtain intermediate 2IV ( ).

[0154] The dosage ratio of the acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and N,N-dimethylformamide D is 0.8 mol: 0.2 mol: 500 mL;

[0155] The dosage of the photoinitiator 1173 is 3 wt% of the total mass of the reactants.

[0156] Its infrared data is as follows: 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1735 cm -1 : ester -C=O exists; 1664 cm -1 : amide -C=O exists; 1187 cm -1 : -P=O exists; 1606 cm -1 、811 cm -1 : -C=C- does not exist.

[0157] S25. Dissolve intermediate 2III and intermediate 2IV in deionized water B, stir for 2.5 h, then defoam. Under stirring conditions, prepare by passing through a spinning device, carding by a carding machine, using the needling method, and then cutting, inspecting, and disinfecting to obtain the functional fiber fabric.

[0158] The dosage ratio of the intermediate 2III, intermediate 2IV, and deionized water B is 8.0 g: 2.0 g: 1000 mL.

[0159] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1725 - 1735 cm -1 : ester - C=O exists; 1664 cm -1 : amide - C=O exists; 1255 cm -1 、1110 cm -1 : -C-O-C- exists; 1187 cm -1 : -P=O exists.

[0160] A preparation method of an artificial meniscus, comprising:

[0161] S31, preparing a mold for making a disc-shaped artificial meniscus.

[0162] S32, arranging a functional fiber fabric on the inner side of the mold.

[0163] S33, adding a modified polyurethane-based material solution into the mold, removing bubbles, and standing still to obtain a formed product I.

[0164] Wherein, the outer end of the artificial meniscus is connected to the functional fiber fabric.

[0165] S34, placing the formed product I in a glutaraldehyde solution for 10 h to obtain a formed product II.

[0166] The preparation method of the glutaraldehyde solution is as follows:

[0167] Adding an aqueous glutaraldehyde solution into acetonitrile, adding a solid water desiccant, sealing and drying for 0.5 h, and then filtering to obtain a glutaraldehyde acetonitrile solution.

[0168] The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and the solid water desiccant is 10 mL: 490 mL: 100 g;

[0169] The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

[0170] S35, placing the formed product II in a calcium bromide solution for 4 h, placing the product in a dialysis bag, dialyzing with deionized water for 3 d, changing the dialysis fluid once a day, and performing freeze-drying to obtain the target product, i.e., the artificial meniscus.

[0171] The concentration of the calcium bromide is 0.04 g / mL.

[0172] Other conditions are the same as in Example 1, except that:

[0173] A method for preparing a modified polyurethane-based material, comprising the following steps:

[0174] S11, under N2 protection, mix hydroxymethyldioxolane and dimethyl carbonate, then add tetrabutyl titanate, stir, heat up to 160 °C, react for 3 h, and perform vacuum distillation to obtain intermediate 1I.

[0175] The molar ratio of the hydroxymethyldioxolane to the dimethyl carbonate is 2:1.

[0176] The dosage of the tetrabutyl titanate is 0.2 wt% of the total mass of the reactants.

[0177] Its infrared data is as follows: 3414 cm -1 : -OH does not exist; 1801 cm -1 : cyclic ester -C=O exists; 1732cm -1 : ester -C=O exists; 1255 cm -1 、1110cm -1 : -C-O-C- exists.

[0178] S12, under N2 protection, add intermediate 1I and diamine to N,N-dimethylformamide A, stir, heat up to 80 °C and react for 8 h, then continue to heat up to 100 °C and react for 2 h; after the reaction, perform vacuum distillation to obtain intermediate 1II.

[0179] The dosage ratio of the intermediate 1I, diamine, and N,N-dimethylformamide A is 1 mol: 1 mol: 400 mL;

[0180] The diamine is added in a molar ratio of 3.0:7.0 of macromolecular diamine to small molecular diamine.

[0181] The macromolecular diamine is polyethylene glycol diamine with a molecular weight of 400.

[0182] The small molecular diamine is a mixture of triethylenetetramine and p-phenylenediamine in a molar ratio of 0.6:0.4.

[0183] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3317 cm -1 : -NH- exists (singlet); 1801 cm -1 : cyclic ester -C=O does not exist; 1725 - 1735cm -1 : ester -C=O exists; 1255 cm -1 、1110cm -1 : -C-O-C- exists.

[0184] S13. Add intermediate product 1II and gelatin into hot N,N-dimethylformamide B, continuously stir at 40 °C for 5 h, and perform vacuum distillation to obtain the target product, i.e., the modified polyurethane-based material.

[0185] The dosage ratio of the intermediate product 1II, gelatin, and N,N-dimethylformamide B is 8.5 g : 1.5 g : 100 mL.

[0186] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists and is enhanced; 1725 - 1735 cm -1 : ester -C=O exists; 1255 cm -1 、1110 cm -1 : -C-O-C- exists.

[0187] A preparation method of a functional fiber fabric includes the following steps:

[0188] S21. Add phthalic acid, polyamine A, and deionized water A into a reaction kettle, under N2 protection, heat to 240 °C, 1.7 MPa, and react for 4 h; reduce to normal pressure and continue to react for 2 h; after the reaction ends, perform vacuum pumping for 1 h to obtain intermediate product 2I.

[0189] The dosage ratio of the phthalic acid, polyamine A, and deionized water A is 2.0 mol : 1.0 mol : 300 mL.

[0190] The polyamine A is added in a molar ratio of 1.0:0 of diamine to triamine; that is, no triamine is added.

[0191] The diamine is polyether diamine with a molecular weight of 500.

[0192] Its infrared data is as follows: 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1664 cm -1 : amide -C=O exists; 3402 cm -1 : -OH exists and weakens; 1764 cm -1 : carboxylic acid -C=O exists and weakens.

[0193] S22. Under N2 protection, add intermediate product 1I and polyamine B into N,N-dimethylformamide C, stir, heat to 100 °C and react for 6 h, then continue to heat to 120 °C and react for 1 h; after the reaction ends, perform vacuum distillation to obtain intermediate product 2II.

[0194] The dosage ratio of the intermediate 1I, polyamine B, and N,N-dimethylformamide C is 0.5 mol: 1.0 mol: 500 mL;

[0195] The polyamine B is added in a molar ratio of 0.8:0.2 of diamine to triamine;

[0196] The diamine is polyether diamine with a molecular weight of 500;

[0197] The triamine is a mixture of melamine and 1,2,3-propanetriamine in a molar ratio of 2.0:1.0.

[0198] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3318 cm -1 : -NH- exists; 1801 cm -1 : Ring -C=O does not exist; 1725 - 1735 cm -1 : -C=O exists; 1255 cm -1 、1110cm -1 : -C-O-C- exists.

[0199] S23, Add the intermediate 2I, intermediate 2II, and deionized water to the reaction kettle, protect with N2, heat up to 255 °C, 1.6 MPa, and react for 3 h; reduce to atmospheric pressure and continue to react for 2.5 h; after the reaction is completed, evacuate for 1 h to obtain the intermediate 2III.

[0200] The dosage ratio of the intermediate 2I, intermediate 2II, and deionized water is added in a ratio of 1.0 mol: 1.0 mol: 300 mL.

[0201] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1764 cm -1 : Carboxylic acid -C=O does not exist; 1725 - 1735 cm -1 : Ester -C=O exists; 1664 cm -1 : Amide -C=O exists; 1255 cm -1 、1110cm -1 : -C-O-C- exists.

[0202] S24. Add acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and photoinitiator 1173 to N,N-dimethylformamide D. Place it under a UV lamp for radiation for 10 min. Then remove the UV lamp and perform vacuum distillation. Add methanol to the concentrate to produce a precipitate. Filter it and take the precipitate. Dry it under vacuum at 60 °C for 8 h to obtain intermediate 2IV ( ).

[0203] The dosage ratio of acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and N,N-dimethylformamide D is 0.7 mol: 0.3 mol: 500 mL;

[0204] The dosage of photoinitiator 1173 is 5 wt% of the total mass of the reactants.

[0205] Its infrared data is as follows: 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1735 cm -1 : ester -C=O exists; 1664 cm -1 : amide -C=O exists; 1187 cm -1 : -P=O exists; 1606 cm -1 , 811 cm -1 : -C=C- does not exist.

[0206] S25. Dissolve intermediate 2III and intermediate 2IV in deionized water B. Stir for 2 h, then defoam. Under stirring conditions, prepare it by passing through a spinning device, carding by a carding machine, and using the needle punching method. Then cut, inspect, and disinfect to obtain a functional fiber fabric.

[0207] The dosage ratio of intermediate 2III, intermediate 2IV, and deionized water B is 9.0 g: 1.0 g: 1000 mL.

[0208] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1725 - 1735 cm -1 : ester -C=O exists; 1664 cm -1 : amide -C=O exists; 1255 cm -1 , 1110 cm -1 : -C-O-C- exists; 1187 cm -1 : -P=O exists.

[0209] A preparation method of an artificial meniscus, comprising:

[0210] S31. Prepare a mold for fabricating a disc-shaped artificial meniscus.

[0211] S32. Arrange a functional fiber fabric inside the mold.

[0212] S33. Add a modified polyurethane-based material solution into the mold, remove air bubbles, let it stand still, and obtain a formed product I.

[0213] Among them, the outer end of the artificial meniscus is connected to the functional fiber fabric.

[0214] S34. Place the formed product I in a glutaraldehyde solution for 5 h to obtain a formed product II.

[0215] The preparation method of the glutaraldehyde solution is as follows:

[0216] Add an aqueous glutaraldehyde solution into acetonitrile, add a solid water desiccant, seal and dry for 0.5 h, then filter to obtain a glutaraldehyde-acetonitrile solution.

[0217] The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and the solid water desiccant is 20 mL: 480 mL: 100 g;

[0218] The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

[0219] S35. Place the formed product II in a calcium bromide solution for 5 h, put the product in a dialysis bag, dialyze with deionized water for 3 d, change the dialysis fluid once a day, and obtain the target product, namely the artificial meniscus, after freeze-drying.

[0220] The concentration of the calcium bromide is 0.01 g / mL.

[0221] Others are the same as in Example 1, and the differences are as follows:

[0222] A preparation method of a modified polyurethane-based material, comprising the following steps:

[0223] S11. Under N2 protection, mix hydroxymethyldioxolane and dimethyl carbonate, then add tetrabutyl titanate, stir, heat up to 180 °C, react for 1 h, and perform vacuum distillation to obtain an intermediate product I.

[0224] The molar ratio of hydroxymethyldioxolane to dimethyl carbonate is 2:1.

[0225] The dosage of tetrabutyl titanate is 0.1 wt% of the total mass of the reactants.

[0226] Its infrared data is as follows: 3414 cm -1 : -OH does not exist; 1801 cm -1 : cyclic ester -C=O exists; 1732 cm-1 : The ester - C=O exists; 1255 cm -1 、1110cm -1 : -C - O - C - exists.

[0227] S12, Protected by N2, add intermediate 1I and diamine into N,N - dimethylformamide A, stir, heat up to 100 °C and react for 6 h, then continue to heat up to 120 °C and react for 1 h; after the reaction, perform vacuum distillation to obtain intermediate 1II.

[0228] The dosage ratio of the intermediate 1I, diamine, and N,N - dimethylformamide A is 1 mol: 1 mol: 400 mL;

[0229] The diamine is added with macromolecular diamine and small - molecular diamine in a molar ratio of 2.0:8.0.

[0230] The macromolecular diamine is polyethylene glycol diamine with a molecular weight of 400.

[0231] The small - molecular diamine is a mixture of triethylenetetramine and p - phenylenediamine in a molar ratio of 0.6:0.4.

[0232] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3317 cm -1 : -NH - exists (singlet); 1801 cm -1 : cyclic ester - C=O does not exist; 1725 - 1735 cm -1 : ester - C=O exists; 1255 cm -1 、1110cm -1 : -C - O - C - exists.

[0233] S13, add intermediate 1II and gelatin into hot N,N - dimethylformamide B, continuously stir at 60 °C for 3 h, and perform vacuum distillation to obtain the target product, i.e., the modified polyurethane - based material.

[0234] The dosage ratio of the intermediate 1II, gelatin, and N,N - dimethylformamide B is 8.5 g: 1.5 g: 100 mL.

[0235] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH - exists and is enhanced; 1725 - 1735 cm -1 : ester - C=O exists; 1255 cm -1 、1110cm -1 : -C - O - C - exists.

[0236] A preparation method of a functional fiber fabric, comprising the following steps:

[0237] S21, Add terephthalic acid, polyamine A, and deionized water A into a reaction kettle, protect with N2, heat up to 260 °C under 1.5 MPa, and react for 2 h; reduce the pressure to atmospheric pressure and continue to react for 3 h; after the reaction is completed, evacuate for 1 h to obtain intermediate 2I.

[0238] The dosage ratio of the terephthalic acid, polyamine A, and deionized water A is 2.0 mol: 1.0 mol: 300 mL.

[0239] The polyamine A is added in a molar ratio of 0.8:0.2 of diamine to triamine;

[0240] The diamine is polyether diamine with a molecular weight of 500;

[0241] The triamine is a mixture of melamine and 1,2,3-propanetriamine in a molar ratio of 4.0:1.0.

[0242] Its infrared data is as follows: 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1664 cm -1 : Amide -C=O exists; 3402 cm -1 : -OH exists and weakens; 1764 cm -1 : Carboxylic acid -C=O exists and weakens.

[0243] S22, Protect with N2, add intermediate 1I and polyamine B into N,N-dimethylformamide C, stir, heat up to 80 °C and react for 8 h, then continue to heat up to 100 °C and react for 2 h; after the reaction is completed, perform vacuum distillation to obtain intermediate 2II.

[0244] The dosage ratio of the intermediate 1I, polyamine B, and N,N-dimethylformamide C is 0.5 mol: 1.0 mol: 500 mL;

[0245] The polyamine B is added in a molar ratio of 1.0:0 of diamine to triamine; that is, no triamine is added.

[0246] The diamine is polyether diamine with a molecular weight of 500.

[0247] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3318 cm -1 : -NH- exists; 1801 cm -1 : Ring -C=O does not exist; 1725 - 1735 cm -1 : -C=O exists; 1255 cm-1 、1110 cm -1 : -C-O-C- exists.

[0248] S23. Add intermediate product 2I, intermediate product 2II, and deionized water into the reaction kettle, protect with N2, heat up to 255 °C, 1.6 MPa, and react for 3 h; reduce to atmospheric pressure and continue to react for 2.5 h; after the reaction is completed, evacuate for 1 h to obtain intermediate product 2III.

[0249] The dosage ratio of the intermediate product 2I, intermediate product 2II, and deionized water is added as 1.0 mol: 1.0 mol: 300 mL.

[0250] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1764 cm -1 : Carboxylic acid -C=O does not exist; 1725 - 1735 cm -1 : Ester -C=O exists; 1664 cm -1 : Amide -C=O exists; 1255 cm -1 、1110 cm -1 : -C-O-C- exists.

[0251] S24. Add acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and photoinitiator 1173 into N,N-dimethylformamide D, irradiate under a UV lamp for 50 min, then remove the UV lamp, perform vacuum distillation, add methanol to the concentrate to produce precipitation, filter, take the precipitate, and dry it in vacuum at 60 °C for 8 h to obtain intermediate product 2IV ( ).

[0252] The dosage ratio of acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and N,N-dimethylformamide D is 0.9 mol: 0.1 mol: 500 mL;

[0253] The dosage of the photoinitiator 1173 is 1 wt% of the total mass of the reactants.

[0254] Its infrared data is as follows: 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1735 cm -1 : Ester -C=O exists; 1664 cm -1 : Amide -C=O exists; 1187 cm -1 : -P=O exists; 1606 cm -1 、811 cm-1 : -C=C- does not exist.

[0255] S25. Dissolve intermediate 2III and intermediate 2IV in deionized water B, stir for 3 h, defoam, and under stirring conditions, prepare by carding through a spinneret device, using the needle punching method, and through cutting, inspection, and disinfection to obtain a functional fiber fabric.

[0256] The dosage ratio of the intermediate 2III, intermediate 2IV, and deionized water B is 7.0 g: 3.0 g: 1000 mL.

[0257] Its infrared data is as follows: 3407 cm -1 : -OH exists; 3322 cm -1 : -NH- exists; 3017 cm -1 : -C-H benzene ring exists; 1725 - 1735 cm -1 : ester -C=O exists; 1664 cm -1 : amide -C=O exists; 1255 cm -1 、1110 cm -1 : -C-O-C- exists; 1187 cm -1 : -P=O exists.

[0258] A preparation method of an artificial meniscus, comprising:

[0259] S31. Prepare a mold for making a disc-shaped artificial meniscus.

[0260] S32. Arrange a functional fiber fabric on the inner side of the mold.

[0261] S33. Add a modified polyurethane-based material solution into the mold, remove bubbles, and let it stand to obtain a formed product I.

[0262] Wherein, the outer end of the artificial meniscus is connected to the functional fiber fabric.

[0263] S34. Place the formed product I in a glutaraldehyde solution for 10 h to obtain a formed product II.

[0264] The preparation method of the glutaraldehyde solution is as follows:

[0265] Add an aqueous glutaraldehyde solution into acetonitrile, add a solid water desiccant, seal and dry for 0.5 h, and then filter to obtain a glutaraldehyde acetonitrile solution.

[0266] The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and solid water desiccant is 10 mL: 490 mL: 100 g;

[0267] The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

[0268] S35. Place the formed product II in a calcium bromide solution for 2 h. Place the product in a dialysis bag and dialyze it with deionized water for 3 d, changing the dialysis fluid once a day. After freeze-drying, the target product, i.e., the artificial meniscus, is obtained.

[0269] The concentration of the calcium bromide is 0.1 g / mL.

[0270] Others are the same as in Example 1, except that:

[0271] In a method for preparing a modified polyurethane-based material, in S12,

[0272] The small molecule diamine is a mixture of triethylenetetramine and p-phenylenediamine at a molar ratio of 0.5:0.5.

[0273] Others are the same as in Example 1, except that:

[0274] In a method for preparing a modified polyurethane-based material, in S12,

[0275] The small molecule diamine is a mixture of triethylenetetramine and p-phenylenediamine at a molar ratio of 0.7:0.3.

[0276] Others are the same as in Example 1, except that:

[0277] In a method for preparing a modified polyurethane-based material, in S13,

[0278] The dosage ratio of the intermediate product 1II, gelatin, and N,N-dimethylformamide B is 7.5 g:2.5 g:100 mL.

[0279] Others are the same as in Example 1, except that:

[0280] In a method for preparing a modified polyurethane-based material, in S13,

[0281] The dosage ratio of the intermediate product 1II, gelatin, and N,N-dimethylformamide B is 9.5 g:0.5 g:100 mL.

[0282] Others are the same as in Example 1, except that:

[0283] In a method for preparing a modified polyurethane-based material, in S12,

[0284] The macromolecule diamine is a mixture of polyethylene glycol diamine and polyether diamine at a mass ratio of 3:1;

[0285] The molecular weight of the polyethylene glycol diamine is 400;

[0286] The molecular weight of the polyether diamine is 500.

[0287] Others are the same as in Example 1, except that:

[0288] In the preparation method of a modified polyurethane-based material, in S13,

[0289] The amino-containing biopolymer is chitosan.

[0290] Others are the same as in Example 1, except that:

[0291] In the preparation method of a functional fiber fabric, in S21 and S22,

[0292] The triamine is a mixture of melamine and 1,3,5-triphenylamine at a molar ratio of 1.0:1.0.

[0293] Others are the same as in Example 1, except that:

[0294] In the preparation method of a functional fiber fabric, in S21 and S22,

[0295] The triamine is a mixture of melamine and 1,3,5-triphenylamine at a molar ratio of 2.0:1.0.

[0296] Others are the same as in Example 1, except that:

[0297] In the preparation method of a functional fiber fabric,

[0298] In S21, the triamine is a mixture of melamine and 1,2,3-propanetriamine at a molar ratio of 2.0:1.0; and,

[0299] In S22, the triamine is a mixture of melamine and 1,2,3-propanetriamine at a molar ratio of 4.0:1.0.

[0300] Others are the same as in Example 1, except that:

[0301] In the preparation method of a functional fiber fabric, in S21,

[0302] The dosage ratio of terephthalic acid, polyamine A, and deionized water A is 1.8 mol:1.0 mol:300 mL.

[0303] Others are the same as in Example 1, except that:

[0304] In the preparation method of a functional fiber fabric, in S22,

[0305] The dosage ratio of intermediate 1I, polyamine B, and N,N-dimethylformamide C is 0.7 mol:1.0 mol:500 mL.

[0306] Others are the same as in Example 1, except that:

[0307] A preparation method of a functional fiber fabric,

[0308] In S21, the dosage ratio of terephthalic acid, polyamine A, and deionized water A is 0.5 mol: 1.0 mol: 300 mL; and,

[0309] In S22, the dosage ratio of intermediate 1I, polyamine B, and N,N-dimethylformamide C is 2.0 mol: 1.0 mol: 500 mL; and,

[0310] In S23, under N2 protection, intermediate 2I and intermediate 2II are added to N,N-dimethylformamide, stirred, heated to 100 °C and reacted for 6 h, and then continuously heated to 120 °C and reacted for 1 h; after the reaction is completed, vacuum distillation is carried out to obtain intermediate 2III.

[0311] The dosage ratio of intermediate 2I, intermediate 2II, and N,N-dimethylformamide is 1 mol: 1 mol: 400 mL.

[0312] The rest is the same as in Example 1, the difference is:

[0313] A preparation method of a functional fiber fabric, in S24,

[0314] The zwitterion is methacryloylethyl sulfobetaine.

[0315] One of the artificial menisci in the following comparative examples is compared with Example 1:

[0316] Comparative Example 1

[0317] The rest is the same as in Example 1, the difference is:

[0318] A preparation method of a modified polyurethane-based material, in S12,

[0319] The diamine is added in a molar ratio of 0:10 of macromolecular diamine and small molecular diamine, that is, no macromolecular diamine is added.

[0320] Comparative Example 2

[0321] The rest is the same as in Example 1, the difference is:

[0322] A preparation method of a modified polyurethane-based material, in S13,

[0323] The dosage ratio of intermediate 1II, gelatin, and N,N-dimethylformamide B is 10 g: 0 g: 100 mL; that is, no gelatin is added.

[0324] Comparative Example 3

[0325] Others are the same as in Example 1, except that:

[0326] A method for preparing a functional fiber fabric,

[0327] In S21, the dosage ratio of terephthalic acid, polyamine A, and deionized water A is 1.0 mol: 1.0 mol: 300 mL; and,

[0328] In S25, the intermediate product 2III is replaced with 2I.

[0329] Implement Comparative Example 4

[0330] Others are the same as in Example 1, except that:

[0331] A method for preparing a functional fiber fabric, comprising the following steps:

[0332] In S22, the dosage ratio of the intermediate product 1I, polyamine B, and N,N-dimethylformamide C is 1.0 mol: 1.0 mol: 500 mL; and,

[0333] In S25, the intermediate product 2III is replaced with 2I.

[0334] Implement Comparative Example 5

[0335] Others are the same as in Example 1, except that:

[0336] A method for preparing a functional fiber fabric, in S21 and S22,

[0337] The polyamine is a diamine.

[0338] Implement Comparative Example 6

[0339] Others are the same as in Example 1, except that:

[0340] A method for preparing a functional fiber fabric, in S21 and S22,

[0341] The polyether diamine is replaced with triethylenetetramine.

[0342] Implement Comparative Example 7

[0343] Others are the same as in Example 1, except that:

[0344] A method for preparing a functional fiber fabric, in S25,

[0345] The dosage ratio of the intermediate product 2III, intermediate product 2IV, and deionized water B is 10.0 g: 0 g: 1000 mL, that is, intermediate product 2IV is not added.

[0346] Implement Comparative Example 8

[0347] Other aspects are the same as those in Example 1, except that:

[0348] In the preparation method of a functional fiber fabric, in S24,

[0349] The dosage ratio of the acrylamide, 2-methacryloyloxyethyl phosphorylcholine, and N,N-dimethylformamide D is 1.0 mol: 0 mol: 500 mL, that is, 2-methacryloyloxyethyl phosphorylcholine is not added.

[0350] Implement Comparative Example 9

[0351] Other aspects are the same as those in Example 1, except that:

[0352] In the preparation method of an artificial meniscus, the impregnation operation with glutaraldehyde acetonitrile solution is not carried out.

[0353] Implement Comparative Example 10

[0354] Other aspects are the same as those in Example 1, except that:

[0355] In the preparation method of an artificial meniscus, the impregnation operation with calcium bromide solution is not carried out.

[0356] Implement Comparative Example 11

[0357] Other aspects are the same as those in Example 1, except that:

[0358] In the preparation method of an artificial meniscus, in S35,

[0359] The calcium bromide is replaced with calcium chloride.

[0360] The physical properties of the artificial menisci prepared in Examples 1-16 and Comparative Examples 1-11 of the present invention were measured respectively, and the results are shown in Table 1.

[0361]

[0362] First, it can be obtained from Examples 1-16 in Table 1 that the artificial meniscus of the present invention has excellent mechanical properties, low friction properties, biocompatibility, and also has properties such as promoting the proliferation and differentiation of chondrocytes.

[0363] Second, from Examples 1 and Comparative Examples 1-2, it can be observed that in the present invention, the artificial meniscus uses a self-made modified polyurethane material as the internal matrix material. After being modified with a macromolecular water-soluble diamine, the mechanical properties can be effectively improved; after being modified with gelatin, the biocompatibility can be improved, and the ability of chondrocyte proliferation and differentiation can be enhanced.

[0364] Thirdly, it can be observed from Example 1 and Comparative Examples 3-8 that in the artificial meniscus of the present invention, a self-made functional fiber fabric is used as the external material, which has the characteristics of improving mechanical properties, low friction performance and promoting bone tissue generation; among them, it can be observed from Comparative Examples 3-4 that the structure of polyamide and polyurethane block has excellent mechanical properties (polyamide has excellent mechanical strength, and polyurethane provides compatibility with polyester, synergistically improving mechanical properties); it can be observed from Comparative Example 5 that some unreacted amino groups in a small amount of triamine act as pendant chains to crosslink with glutaraldehyde, improving the overall mechanical properties; it can be observed from Comparative Examples 6-7 that water-soluble diamine can, on the one hand, provide toughness to improve mechanical properties; on the other hand, it provides hydrophilicity and synergistically with the polyamide copolymer to provide hydrophilicity, improving the lubrication performance between the artificial meniscus and cartilage tissue and reducing the friction coefficient; it can be observed from Comparative Examples 7-8 that the polyamide / zwitterionic copolymer effectively improves the lubrication performance between the artificial meniscus and cartilage tissue, reduces wear and bruising; and, the ammonium salt, phosphate or sulfonate in the zwitterionic structure is similar to the cell composition structure, which can promote joint lubrication, reduce inflammation and protect cartilage.

[0365] Fourthly, it can be observed from Example 1 and Comparative Examples 9-11 that the artificial meniscus of the present invention has excellent mechanical properties and the function of promoting cartilage tissue proliferation; among them, it can be observed from Comparative Example 9 that glutaraldehyde can be used as a crosslinking agent to improve mechanical properties; it can be observed from Comparative Examples 10-11 that calcium ions have an auxiliary effect on improving mechanical properties; bromide ions have the function of inducing the regeneration and differentiation of chondrocytes, and can effectively promote cartilage repair; it can compensate for cartilage tissue wear and effectively extend the service life of the material.

[0366] In summary, the artificial meniscus of the present invention uses a self-made modified polyurethane material as the internal matrix material and a self-made functional fiber fabric as the external binding material, and is prepared by crosslinking calcification, having obvious advantages in mechanical properties, low wear and promoting chondrocyte proliferation.

[0367] The test methods are as follows:

[0368] (1) Tensile strength and elongation at break: Test according to the method described in GB / T 1040.3-2006. The test samples are immersed in a 37°C sterile phosphate buffer solution for 0, 48, and 96 days, taken out and stabilized to room temperature for testing.

[0369] (2) Coefficient of friction: Test was conducted using a friction testing machine (BRUKER UMT) under the conditions of reciprocating motion, 1 Hz frequency, 0.4 N load, simulated synovial fluid lubrication, porcine femoral condyle cartilage as the friction pair, and room temperature. The test was terminated when the coefficient of friction became constant. The samples to be tested were immersed in sterile phosphate buffer solution at 37 °C for 0, 48, and 96 days, taken out and stabilized to room temperature before testing.

[0370] (3) Cytotoxicity: Referring to the standard GB / T 16886.5 - 2003, after the material was immersed in the culture medium for 7 and 14 days, the extract was taken to culture NIH3T3 cells, and then cytotoxicity assessment was carried out (when the relative cell survival rate > 80%, it was considered that the biocompatibility was good).

[0371] (4) Cell differentiation test: On the 14th day of ATDC5 cell culture, the content of glycosaminoglycan (GAG) secreted by the cultured ATDC5 differentiated into chondrocytes was quantitatively detected, and the content of dsDNA (double-stranded DNA) was measured. The content per microgram of dsDNA was calculated, and then the data was normalized.

[0372] Preparation of papain lysate:

[0373] Dissolve the following components in PBS: 50 mM Na3PO4, 20 mM N-acetyl cysteine, 28 μL / mL papain, filter through a 0.22 μm filter membrane and store at 4 °C.

[0374] Lysis of cells:

[0375] Transfer the cultured monolayer cells or cell aggregates to a well plate, wash twice with PBS, add 300 μL of papain lysate to the well plate, seal with a sealing film, incubate in a water bath at 60 °C for 16 h. After completion, centrifuge the well plate, and pipette the lysate with a 200 μL pipette tip to mix evenly. Transfer the lysate to a 1.5 mL EP tube, centrifuge and take the supernatant, and immediately measure or store at -80 °C for later use. This sample is used for the determination of double-stranded DNA (dsDNA) and GAG content.

[0376] Determination of dsDNA content:

[0377] Take the lysate sample obtained from cell lysis and test the concentration of dsDNA using a Nanodrop instrument.

[0378] Determination of GAG content:

[0379] The lysate sample obtained by cell lysis was reacted with the DMMB staining solution at a volume ratio of 1:6. After completion, the absorbance at 525 nm was measured on an enzyme-linked immunosorbent assay (ELISA) reader, standardized by the dsDNA content, and the relative content of GAG per microgram of dsDNA was calculated.

[0380] Inspired by the ideal embodiments of the present invention described above, through the above description, relevant staff can make various changes and modifications completely within the scope not deviating from the technical idea of the present invention. The technical scope of the present invention is not limited to the content in the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A preparation method of an artificial meniscus, characterized in that, Comprising: S31, preparing a mold for making a disc-shaped artificial meniscus; S32, arranging a functional fiber fabric inside the mold; S33, adding a modified polyurethane-based material solution into the mold, removing bubbles, and standing still to obtain Form I; Wherein, the outer end of the artificial meniscus is connected to the functional fiber fabric; S34, placing Form I in a glutaraldehyde solution for 5 - 10 h to obtain Form II; S35, placing Form II in a calcium bromide solution for 2 - 5 h to obtain the target product, i.e., the artificial meniscus; The preparation method of the modified polyurethane-based material comprises the following steps: S11, performing an ester exchange reaction on hydroxymethyldioxolane and dimethyl carbonate to obtain Intermediate I; S12, performing a ring-opening reaction on Intermediate I and a diamine to obtain Intermediate II; S13, blending Intermediate II with a bio-macromolecule containing an amino group to obtain the target product, i.e., the modified polyurethane-based material; The preparation method of the functional fiber fabric comprises the following steps: S21, performing a condensation reaction on a dibasic acid and polyamine A to obtain Intermediate 2I; S22, performing a ring-opening reaction on Intermediate 1I and polyamine B to obtain Intermediate 2II; S23, performing a polycondensation reaction on Intermediate 2I and Intermediate 2II to obtain Intermediate 2III; S24, performing a free radical polymerization on acrylamide and zwitterion to obtain Intermediate 2IV; S25, blending Intermediate 2III and Intermediate 2IV, and performing spinning and carding to obtain the functional fiber fabric.

2. The preparation method according to claim 1, wherein The molar ratio of hydroxymethyldioxolane to dimethyl carbonate is 2:

1.

3. The preparation method according to claim 1, wherein The molar ratio of Intermediate I to the diamine is 1:1; and The diamine is added in a molar ratio of 2.0 - 3.0:7.0 - 8.0 of macromolecular diamine to small molecular diamine.

4. The preparation method according to claim 3, wherein The macromolecular diamine is polyethylene glycol diamine or / and polyether diamine; and The small molecular diamine is a mixture of aliphatic diamine and aromatic diamine.

5. The preparation method according to claim 1, wherein The dosage ratio of Intermediate II to the bio-macromolecule containing an amino group is 7.5 - 9.5 g:0.5 - 2.5 g; and The bio-macromolecule containing an amino group includes gelatin and chitosan.

6. The preparation method according to claim 1, wherein The molar ratio of the dibasic acid to polyamine A is 0.5 - 2.0:1.0; and, The dibasic acid includes terephthalic acid; Polyamine A is added in a molar ratio of 0.8 - 1.0:0 - 0.2 of diamine to triamine; The diamine is a water-soluble diamine; Including polyether diamine; The triamine includes melamine.

7. The preparation method according to claim 1, wherein The molar ratio of Intermediate I to polyamine B is 0.5 - 2.0:1.0; and, The polyamine A is added in a molar ratio of 0.8 - 1.0:0 - 0.2 of diamine to triamine; The diamine is a water-soluble diamine; including polyether diamine; The triamine includes melamine.

8. The preparation method according to claim 1, wherein The intermediate 2I and the intermediate 2II are added in a molar ratio of 1.0:1.

0.

9. The preparation method according to claim 1, wherein The molar ratio of acrylamide to zwitterion is 0.7 - 0.9:0.1 - 0.3; and The zwitterion is phosphorylcholine or betaine.

10. The preparation method according to claim 1, wherein The dosage ratio of the intermediate 2III to the intermediate 2IV is 7.0 - 9.0 g:1.0 - 3.0 g.

11. The preparation method according to claim 1, wherein The preparation method of the glutaraldehyde solution is as follows: Adding an aqueous glutaraldehyde solution into acetonitrile, adding a solid water desiccant, sealing and drying for 0.5 h, and then filtering to obtain a glutaraldehyde acetonitrile solution; The dosage ratio of the aqueous glutaraldehyde solution, acetonitrile, and solid water desiccant is 10 - 20 mL:480 - 490 mL:100 g; The concentration (w / v) of the aqueous glutaraldehyde solution is 50%.

12. The preparation method according to claim 1, wherein The concentration of calcium bromide is 0.01 - 0.1 g / mL.

13. An artificial meniscus, characterized in that, Prepared by the preparation method according to any one of claims 1 - 12.

Images