A modified bone cement, its preparation method and application

Abstract

This invention provides a modified bone cement, its preparation method, and its application. The raw materials for preparing the modified bone cement include: nanospheres, a combination of methacrylic acid monomers and polymethyl methacrylate (PMMA). The nanospheres consist of: polycitrate, polyacrylate elastomer, and a dispersant, with a molar ratio of polycitrate to polyacrylate elastomer of (1-9):1. The nanospheres have a particle size of less than 200 nanometers. The polycitrate in the nanospheres is degradable and absorbable, improving the integration of PMMA bone cement with human bone tissue and enhancing the interfacial adhesion between the nanospheres and PMMA bone cement. The introduction of polyacrylate elastomer into the nanospheres prolongs the storage stability of the nanospheres within the methacrylic acid monomers, improving the compatibility between the nanospheres and PMMA bone cement. This extends the final setting time of the modified bone cement and significantly reduces the heat release during PMMA curing.

Description

Technical Field

[0001] This invention belongs to the field of biomaterials technology, specifically relating to a modified bone cement, its preparation method, and its application. Background Technology

[0002] With an aging population and changing lifestyles, the number of bone-related diseases is increasing. Injectable bone cement is widely used in clinical orthopedics for vertebral compression fractures, knee and hip replacement surgery, pedicle screw fixation, and the treatment of bone tumors and defects due to its excellent load-bearing capacity and good filling properties.

[0003] Currently, the most commonly used bone cement in clinical orthopedics is polymethyl methacrylate (PMMA), which has advantages such as good biocompatibility, injectability, plasticity, suitable viscosity, and excellent mechanical strength, and is widely used to fill medullary cavities and gaps. However, PMMA also has obvious disadvantages, such as: (1) its high mechanical strength can easily cause fractures of adjacent vertebrae; (2) the high temperature released during the polymerization reaction of MMA monomers can cause irreversible thermal damage to surrounding tissues, which is not conducive to subsequent bone tissue repair; (3) PMMA is a bioinert material that is almost non-degradable in vivo and cannot induce new bone growth in vivo, resulting in poor bonding between the material and surrounding bone tissue. Long-term implantation may lead to aseptic loosening of the material or prosthesis. At present, there are also some bioactive inorganic bone cements, such as calcium phosphate bone cement, calcium sulfate bone cement, and magnesium phosphate bone cement, which have certain osteoinductive and osteoconductive properties. However, due to their poor mechanical strength and long molding time, their widespread use is limited. PMMA bone cement is still the most commonly used bone cement material in clinical practice. Controlling and modifying PMMA bone cement to lower its polymerization temperature and elastic modulus while improving its osteogenic activity and promoting osseointegration is a major challenge.

[0004] To overcome these drawbacks, the modification of PMMA-based bone cement has been extensively studied. The main direction of modification research is the addition of bioactive materials to PMMA bone cement.

[0005] In recent years, biomaterials based on polycitrate have received increasing attention in medical applications such as bone repair due to their advantages such as good biocompatibility, biomimetic elastic behavior, biodegradability and tissue repair activity.

[0006] There is an urgent clinical need for bone cement that is biodegradable, has moderate mechanical properties, and strong osteoinduction and osseointegration capabilities. Summary of the Invention

[0007] In view of the shortcomings of the prior art, the purpose of this invention is to provide a modified bone cement, its preparation method and application, which prolongs the final setting time of the modified bone cement, provides surgeons with more convenient operation, reduces the heat release of the bone cement curing reaction, and provides better tissue conditions for subsequent bone repair.

[0008] This invention improves the interfacial adhesion between nanospheres and PMMA bone cement from a materials science perspective, prolongs the storage stability of nanospheres in methacrylic acid monomer, and enhances the compatibility between nanospheres and PMMA bone cement.

[0009] To achieve this objective, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a modified bone cement, wherein the raw materials for preparing the modified bone cement include: nanospheres, a combination of methacrylic acid monomers and polymethyl methacrylate, wherein the components of the nanospheres include: a combination of polycitrate, polyacrylate elastomer and dispersant, wherein the molar ratio of polycitrate to polyacrylate elastomer is (1-9):1, for example, it can be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, and specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0011] To overcome the limitations of polycitrate, a composite polycitrate-polyacrylate elastomer (POC-A) nanosphere was developed. POC-A exhibits a representative organic molecular structure, significantly enhancing the elastomer's mechanical strength, osteogenic capacity, and antibacterial and antioxidant activity. Further studies have shown that POC-A-based nanoparticles, films, and scaffolds can be used for bioimaging, significantly improving bone regeneration and soft tissue repair. Adding nanospheres as a bioactive functional component to PMMA allows for the preparation of highly active, biodegradable, and biomechanically adapted bone cement.

[0012] This invention develops a method for preparing nanosphere-modified bone cement. The addition of nanospheres increases the injectability and hydrophilicity of the bone cement and effectively reduces the polymerization temperature. It also possesses biodegradability, antioxidant and antibacterial properties, and enhanced osteogenic function.

[0013] Preferably, the particle size of the nanospheres is ≤200nm, for example, it can be 1nm, 5nm, 10nm, 50nm, 100nm, 150nm, 200nm, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0014] Preferably, the methacrylate monomers include any one or a combination of at least two of methyl methacrylate, butyl methacrylate, ethyl methacrylate, propyl methacrylate, or isobornyl methacrylate.

[0015] Preferably, the mass ratio of the nanospheres to polymethyl methacrylate is 1:(4-20), for example, it can be 1:4, 1:5, 1:8, 1:10, 1:12, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0016] Preferably, the mass ratio of polymethyl methacrylate to methacrylic monomer is 1:3-3:1, for example, it can be 1:1, 1:2, 1:3, 1.5:1, 2:1, 2.5:1, 3:1, and specific values ​​between the above points. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0017] Preferably, the polyacrylate elastomer comprises any one or a combination of at least two of propylene-acrylate-vinyl acetate, ethylene-acrylate copolymer, or epoxy-acrylate copolymer.

[0018] Preferably, the dispersant comprises any one or a combination of at least two of surfactants, aqueous dispersants, or polyurethane dispersants.

[0019] Preferably, the mass ratio of the polycitric acid ester to the dispersant is 100:(0.1-5), for example, it can be 100:0.1, 100:0.5, 100:1, 100:2, 100:3, 100:4, 100:5, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0020] In a second aspect, the present invention provides a method for preparing modified bone cement as described in the first aspect, characterized in that the preparation method comprises:

[0021] (1) Polycitric acid ester, polyacrylate elastomer and dispersant are mixed to obtain nanospheres;

[0022] (2) The nanospheres obtained in step (1) are mixed with methacrylic acid monomers to obtain the material;

[0023] (3) The material obtained in step (2) is mixed with polymethyl methacrylate and subjected to a curing reaction to obtain the modified bone cement.

[0024] Preferably, in step (1), the polycitric acid ester, polyacrylate elastomer and organic solvent are mixed to obtain a composite material solution, and the composite material solution and dispersant are mixed, dispersed, centrifuged and freeze-dried to obtain nanospheres.

[0025] Preferably, the mixing in step (1) is carried out in the presence of an organic solvent;

[0026] Preferably, the organic solvent includes any one or a combination of at least two of dichloromethane, chloroform, acetone, butanone, ethyl acetate, butyl acetate, dimethylformamide, or dimethyl sulfoxide.

[0027] Preferably, the concentration of the composite material solution is 20 wt%.

[0028] Preferably, the preparation method of the nanospheres in step (1) specifically includes: mixing polycitric acid ester, polyacrylate elastomer and organic solvent for the first time to obtain a composite material solution, mixing the composite material solution with a dispersant for the second time, and dispersing, centrifuging and freeze-drying to obtain the nanospheres.

[0029] Preferably, the dispersion time is 3-5 hours, for example, it can be 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, and specific point values ​​between the above point values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific point values ​​included in the range.

[0030] Preferably, the centrifugation time is 5-30 min, for example, it can be 5 min, 6 min, 8 min, 10 min, 15 min, 20 min, 30 min, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range.

[0031] Preferably, the centrifugation rate is 6000-20000 rpm, for example, it can be 6000 rpm, 7000 rpm, 10000 rpm, 12000 rpm, 15000 rpm, 18000 rpm, 20000 rpm, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0032] Preferably, the freeze-drying time is 3-10 hours, for example, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range.

[0033] Preferably, the freeze-drying temperature is -40 to -5°C, for example, it can be -40°C, -30°C, -20°C, -10°C, -5°C, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0034] Preferably, the curing reaction temperature in step (3) is 25-90℃, for example, it can be 25℃, 30℃, 50℃, 80℃, 90℃, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0035] Preferably, the curing reaction time is 5-15 min, for example, it can be 5 min, 6 min, 8 min, 10 min, 15 min, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0036] The specific preparation method of the nanospheres includes:

[0037] S1: Dissolve polycitrate and polyacrylate elastomers separately in an organic solvent to obtain a composite material solution;

[0038] S2: Disperse the dispersant in water to obtain an aqueous solution of the dispersant;

[0039] S3: Slowly add the composite material solution to the dispersant aqueous solution, turn on the homogenizer to stir, and after the addition is finished, continue stirring for 3-5 hours to obtain the composite material microsphere dispersion.

[0040] S4. Centrifuge the S3 composite microsphere dispersion at 6000-20000 rpm for 5-30 minutes. Particles larger than 200 nm will be deposited at the bottom of the centrifuge tube. Collect the supernatant in the centrifuge tube and freeze-dry to obtain nanospheres with a particle size ≤200 nm.

[0041] S1: The ratio of polycitric acid ester to polyacrylic acid elastomer is 1:1-9:1, and the polyacrylic acid ester elastomer can be propylene-acrylate-vinyl acetate ester, ethylene-acrylate copolymer, or epoxy-acrylate copolymer.

[0042] The solvent for dissolving the composite material can be a polar organic solvent such as dichloromethane, chloroform, acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, dimethylformamide, or dimethyl sulfoxide. The dispersant has a mass concentration of 10-30% and can be a water-soluble dispersant such as F-127 surfactant, aqueous PAA dispersant, or polyurethane dispersant.

[0043] Among them, the S3 composite material dispersion is dispersed in a slow-accelerated dispersion using a homogenizer for 3-5 hours.

[0044] The S4 centrifuge is performed at a speed of 6000-20000 rpm for 5-30 minutes. The supernatant is then freeze-dried to obtain nanospheres with a particle size of less than or equal to 200 nanometers.

[0045] The preparation method of the modified bone cement specifically includes:

[0046] The nanospheres are uniformly dispersed in a methacrylic acid monomer component and stored. When needed, the nanosphere dispersion is mixed with polymethacrylic acid ester. The powder-to-liquid weight ratio is 1:3-3:1, and the mixture is rapidly stirred to prepare modified bone cement.

[0047] Thirdly, the present invention provides the application of modified bone cement as described in the first aspect in orthopedic bioactive materials.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] The modified bone cement provided by this invention features polycitrate nanospheres that are biodegradable and absorbable. The addition of nanospheres with a particle size of less than 200 nanometers improves the biocompatibility of PMMA bone cement. The reactive active groups on the surface of the nanospheres can react with methacrylic monomers, enhancing the interfacial adhesion between the nanospheres and PMMA bone cement. The introduction of polyacrylic elastomers into the nanospheres prolongs their storage stability with methacrylic monomers, further improving their compatibility with PMMA bone cement. The introduction of nanospheres extends the final setting time of the modified bone cement to 10.3-15.2 minutes, providing surgeons with easier operation. The introduction of nanospheres significantly reduces the heat release during PMMA curing, providing better tissue conditions for subsequent bone repair. The modified bone cement has a compressive modulus of 750-1250 MPa and a compressive strength of 74-117 MPa. The modified bone cement material has good extracellular anti-inflammatory effects, effectively reducing the expression level of inflammatory factors in RAW cells after stimulation. Its good anti-inflammatory effect provides a good microenvironment for cells, which is beneficial to osteogenic differentiation and angiogenesis during the bone defect repair process. Detailed Implementation

[0050] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0051] The experimental materials used in the embodiments and comparative examples of this invention are as follows:

[0052] (1) Source of polycitric acid ester (POC): Polycitric acid ester was synthesized using citric acid, glycerol and aminopropyl isobutyl POSS as raw materials, according to Example 1 of CN105504251A.

[0053] (2) Polyacrylate elastomer DP: DuPont, Inc., USA;

[0054] (3) Pluronic F-127 surfactant: BASF GmbH, Germany;

[0055] (4) Tetrahydrofuran: Sinopharm Reagent;

[0056] (5) Ethyl acetate: National Pharmaceutical Reagent;

[0057] (6) Hydroxycyclohexane: National Pharmaceutical Reagent;

[0058] (7) Polymethyl methacrylate: Heraeus (Germany) GmbH;

[0059] (8) Methyl methacrylate (MMA): Heraeus (Germany) Ltd.

[0060] Example 1

[0061] This embodiment provides a modified bone cement and its preparation method. The raw materials for preparing the modified bone cement include a combination of nanospheres, polymethyl methacrylate (PMMA), and methyl methacrylate (MMA). The mass ratio of nanospheres to PMMA is 1:20, and the powder-liquid weight ratio of PMMA to MMA is 2:1. The raw materials for preparing the nanospheres include: polycitrate and polyacrylate elastomer in a mass ratio of 1:1, and 15 mL of an aqueous solution of 12.5 wt% Pluronic F-127.

[0062] The specific preparation method is as follows:

[0063] Polycitrate and polyacrylate elastomers were dissolved in tetrahydrofuran solvent to prepare a 20 wt% tetrahydrofuran solution of the composite material. Simultaneously, Pluronic F-127 surfactant was dissolved in water to prepare a 12.5 wt% aqueous solution of Pluronic F-127.

[0064] Add 5 mL of the composite material solution to a Pluronic F-127 aqueous solution and then to a 50 mL centrifuge tube. Stir the mixture at 6000 rpm for 3 hours using a high-speed homogenizer (DISPERMAT, CN10 VMA). Centrifuge the mixture at 6000 rpm for 5 minutes, collect the supernatant, and freeze-dry it for 3 hours to obtain nanospheres with a diameter of 150 nm.

[0065] The nanospheres were dispersed in methyl methacrylate for storage.

[0066] In use, methyl methacrylate with added nanospheres is rapidly stirred with polymethyl methacrylate for 3 minutes and then injected into a precast mold. The mixture is then cured at 25°C for 5 minutes to prepare modified bone cement.

[0067] Example 2

[0068] This embodiment provides a modified bone cement and its preparation method. The raw materials for preparing the modified bone cement include a combination of nanospheres, polymethyl methacrylate (PMMA), and butyl methacrylate (BMA). The mass ratio of PMMA to PMMA is 1:20, and the powder-liquid weight ratio of PMMA to BMA is 2:1. The raw materials for preparing the PMMA include: polycitrate and polyacrylate elastomer in a mass ratio of 3:1, and 15 mL of an aqueous solution of 12.5 wt% Pluronic F-127.

[0069] The preparation method specifically includes the following:

[0070] Polycitrate and polyacrylate elastomers were dissolved in tetrahydrofuran solvent to prepare a 20 wt% tetrahydrofuran solution of the composite material. Simultaneously, Pluronic F-127 surfactant was dissolved in water to prepare a 12.5 wt% aqueous solution of Pluronic F-127.

[0071] Add 5 mL of the composite material solution and Pluronic F-127 aqueous solution to a 50 mL centrifuge tube. Stir the mixture at 8000 rpm for 3 hours using a high-speed homogenizer (DISPERMAT, CN10 VMA). Centrifuge the mixture at 9000 rpm for 5 minutes, collect the supernatant, and freeze-dry for 3 hours to obtain 120 nm microspheres. Disperse the microspheres in butyl methacrylate for storage.

[0072] In use, butyl methacrylate with added nanospheres is rapidly stirred with polymethyl methacrylate for 3 minutes and then injected into a precast mold. The mixture is then cured at 90°C for 15 minutes to prepare modified bone cement.

[0073] Example 3

[0074] This embodiment provides a modified bone cement and its preparation method. The raw materials for preparing the modified bone cement include a combination of nanospheres, polymethyl methacrylate (PMMA), and ethyl methacrylate (EMA). The mass ratio of PMMA to PMMA is 1:20, and the powder-liquid weight ratio of PMMA to EMA is 2:1. The raw materials for preparing the nanospheres include: polycitrate and polyacrylate elastomer in a mass ratio of 10:1, and 15 mL of an aqueous solution of 12.5 wt% Pluronic F-127.

[0075] The preparation method specifically includes the following:

[0076] Polycitrate and polyacrylate elastomers were dissolved in tetrahydrofuran solvent to prepare a 20 wt% tetrahydrofuran solution of the composite material. Simultaneously, Pluronic F-127 surfactant was dissolved in water to prepare a 12.5 wt% aqueous solution of Pluronic F-127.

[0077] 5 mL of the composite material solution and Pluronic F-127 aqueous solution were added to a 50 mL centrifuge tube. The mixture was stirred at 8000 rpm for 3 hours using a high-speed homogenizer (DISPERMAT, CN10 VMA). The mixture was then centrifuged at 5000 rpm for 5 minutes, the supernatant was collected, and the mixture was freeze-dried for 3 hours to obtain modified 80 nm microspheres. The microspheres were dispersed in ethyl methacrylate for storage.

[0078] In use, ethyl methacrylate with added nanospheres is rapidly stirred with polymethyl methacrylate for 3 minutes and then injected into a precast mold. The mixture is then cured at 25°C for 5 minutes to prepare modified bone cement.

[0079] Example 4

[0080] This embodiment provides a modified bone cement and its preparation method. The raw materials for preparing the modified bone cement include a combination of nanospheres, polymethyl methacrylate (PMMA), and methyl methacrylate (MMA). The mass ratio of nanospheres to PMMA is 1:20, and the powder-liquid weight ratio of PMMA to MMA is 2:1. The raw materials for preparing the nanospheres include: polycitrate and polyacrylate elastomer in a mass ratio of 10:1, and 15 mL of an aqueous solution of 30 wt% Pluronic F-127.

[0081] The preparation method specifically includes the following:

[0082] A 20 wt% tetrahydrofuran solution of the composite material was prepared by dissolving polycitrate and polyacrylate elastomers in tetrahydrofuran solvent. Simultaneously, a 30 wt% aqueous solution of Pluronic F-127 surfactant was prepared by dissolving Pluronic F-127 surfactant in water.

[0083] Add 5 mL of the composite material solution and F-127 solution to a 50 mL centrifuge tube, and stir the mixture at 10,000 rpm for 3 hours using a high-speed homogenizer (DISPERMAT, CN10 VMA). Centrifuge the mixture at 5,000 rpm for 5 minutes, collect the supernatant, and freeze-dry it for 3 hours to obtain 105 nm microspheres.

[0084] Modified bone cement was prepared by rapidly mixing nanospheres with PMMA for 3 minutes and then injecting the mixture into a precast mold, followed by curing at 25°C for 5 minutes.

[0085] Example 5

[0086] This embodiment provides a modified bone cement and its preparation method. The raw materials for preparing the modified bone cement include a combination of nanospheres, polymethyl methacrylate (PMMA), and methyl methacrylate (MMA). The mass ratio of nanospheres to PMMA is 1:20, and the powder-to-liquid weight ratio of PMMA to MMA monomer is 2:1. The raw materials for preparing the nanospheres include: polycitrate and polyacrylate elastomer in a mass ratio of 10:1, and 15 mL of an aqueous solution of 12.5 wt% Pluronic F-127.

[0087] The preparation method specifically includes the following:

[0088] Polycitric acid ester and polyacrylate elastomer were mixed and mixed in an internal mixer at 180°C for 20 minutes to prepare a composite material. A 20 wt% solution of the composite material in tetrahydrofuran and a 30 wt% aqueous solution of polyethylene glycol-polypropylene glycol-polyethylene glycol triblock copolymer (F-127) were prepared.

[0089] Add 5 mL of the composite material solution and Pluronic F-127 aqueous solution to a 50 mL centrifuge tube. Stir the mixture at 8000 rpm for 3 hours using a high-speed homogenizer (DISPERMAT, CN10 VMA). Centrifuge the mixture at 5000 rpm for 10 minutes, collect the supernatant, and freeze-dry for 3 hours to obtain 100 nm microspheres. Disperse the microspheres in methyl methacrylate for storage.

[0090] Modified bone cement was prepared by rapidly mixing nanospheres with PMMA for 3 minutes and then injecting the mixture into a precast mold, followed by curing at 25°C for 5 minutes.

[0091] Comparative Example 1

[0092] This comparative example provides a modified bone cement, which differs from Example 1 only in that it does not contain polyacrylate elastomer, and the amount of nanospheres used is the same as the total mass of nanospheres and polyacrylate elastomer in Example 1.

[0093] Comparative Example 2

[0094] This comparative example provides a modified bone cement, which differs from Example 4 only in the use of polycitrate and polyacrylate elastomers. DP quality ratio 11 / 1.

[0095] Comparative Example 3

[0096] This comparative example provides a modified bone cement and its preparation method. Polycitrate is directly added to the liquid phase of methyl methacrylate at a mass ratio of 3:7 to obtain a polycitrate-methyl methacrylate mixture. The mixture is then rapidly stirred with PMMA at a weight ratio of 2:1 for 3 minutes and injected into a precast mold to prepare the modified bone cement.

[0097] The modified bone cements provided in Examples 1-5 and Comparative Examples 1-3 were subjected to performance tests, and the specific methods are as follows:

[0098] Nanosphere dispersion stability test: Nanospheres were dispersed in MMA liquid component to prepare a dispersion with a nanosphere content of 30%. The stability of the nanosphere dispersion was evaluated at 50℃ and the state of the nanosphere dispersion was evaluated after storage for 3 months, 6 months, 12 months and 18 months.

[0099] (2) Injection rate: At 25°C, the mixed slurry is poured into the top of the glass from a 60° angle, and the flow time of the slurry is observed until the slurry stops flowing. The time is recorded.

[0100] (3) Setting time: Refer to YY / T1697;

[0101] (4) Dispersibility: Disperse the nanospheres and acrylate monomers at a mass ratio of 1 / 2 under ultrasonication for 60 minutes, and observe the appearance of the solution to see if it is turbid or has precipitate.

[0102] (5) Compression modulus: GB / T14694;

[0103] (6) Compressive strength: GB / T14694;

[0104] (7) Anti-inflammatory properties: The in vitro anti-inflammatory properties of the material were evaluated by detecting the expression levels of inflammatory cytokines in cells. RAW264.7 cells were cultured at 2 × 10⁶ cells per well. 5Cells were seeded at a density of 5 cells (n=5) in 12-well plates. After 12 hours of adhesion, the normal group was treated with fresh medium, while the other groups were stimulated with 100 ng / mL LPS for 18 hours. Then, the model group was replaced with normal medium, and the material group was replaced with fresh medium containing different concentrations of bone cement extract and cultured for 2 days. The expression levels of IL-6 and TNF-α in the cells were detected by quantitative reverse transcription polymerase chain reaction.

[0105] The modified bone cements obtained in Examples 1-5 and Comparative Examples 1-3 were tested according to the above performance testing methods. The test results are shown in Table 1.

[0106] Table 1

[0107] 3 months 6 months 12 months 18 months Example 1 Clarity and transparency Clarity and transparency Clarity and transparency Clarity and transparency Example 2 Clarity and transparency Clarity and transparency Clarity and transparency Clarity and transparency Example 3 Clarity and transparency Clarity and transparency Clarity and transparency Clarity and transparency Example 4 Clarity and transparency Clarity and transparency Clarity and transparency Clarity and transparency Example 5 Clarity and transparency Clarity and transparency Clarity and transparency Clarity and transparency Comparative Example 1 Clarity and transparency Slightly cloudy turbid precipitation Comparative Example 2 Slightly cloudy precipitation precipitation precipitation Comparative Example 3 Clarity and transparency Clarity and transparency Slight turbidity turbid

[0108] The nanospheres are uniformly dispersed in MMA liquid. The introduction of acrylate elastomer into the nanospheres improves the thermal storage stability of the nanospheres in the MMA liquid composition. The thermal stability exceeds 18 months, and there is no turbidity or precipitation.

[0109] Table 2

[0110]

[0111]

[0112] The data above show that the introduction of nanospheres reduces bone cement volume and increases bone cement injection rate; the introduction of nanospheres also reduces polymer heat release. The introduction of polyacrylic acid elasticity improves the compatibility of nanospheres with PMMA bone cement.

[0113] Table 3

[0114] Compression modulus / MPa Compressive strength / MPa Example 1 1250 117 Example 2 1000 95 Example 3 815 85 Example 4 750 74 Example 5 780 79 Comparative Example 1 1300 134 Comparative Example 2 289 49 Comparative Example 3 259 32

[0115] The data above show that the introduction of nanospheres reduces the compressive modulus of bone cement, resulting in better matching of mechanical properties with the implantation site and reducing the risk of stress concentration and postoperative refracture. Furthermore, although the compressive strength of the modified bone cement is somewhat reduced, its mechanical strength (compressive strength) of 74 MPa is still higher than the 70 MPa lower limit specified in ISO 5833, providing good stability assurance.

[0116] Table 4

[0117]

[0118]

[0119] Orthopedic bioactive materials often induce macrophage-mediated immune responses after implantation. The in vitro anti-inflammatory properties of modified bone cement were evaluated. The modified bone cement group effectively reduced the expression levels of inflammatory factors in RAW cells after stimulation.

[0120] The applicant declares that this invention illustrates a modified bone cement, its preparation method, and its application through the above embodiments. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

Claims

1. A modified bone cement, characterized in that, The raw materials for preparing the modified bone cement include nanospheres, a combination of methacrylic monomers and polymethyl methacrylate, wherein the nanospheres include a combination of polycitrate, polyacrylate elastomer and dispersant, and the mass ratio of polycitrate to polyacrylate elastomer is (1-9):

1. The particle size of the nanospheres is ≤200 nm; The mass ratio of the nanospheres to polymethyl methacrylate is 1:(4-20). The polyacrylate elastomer includes any one or a combination of at least two of propylene-acrylate-vinyl acetate, ethylene-acrylate copolymer, or epoxy-acrylate copolymer; The polycitric acid ester is synthesized from citric acid, glycerol and aminopropyl isobutyl POSS.

2. The modified bone cement according to claim 1, characterized in that, The methacrylate monomers include any one or a combination of at least two of methyl methacrylate, butyl methacrylate, ethyl methacrylate, propyl methacrylate, or isobornyl methacrylate.

3. The modified bone cement according to claim 1, characterized in that, The mass ratio of polymethyl methacrylate to methacrylic monomers is 1:3-3:

1.

4. The modified bone cement according to claim 1, characterized in that, The dispersant includes any one or a combination of at least two of surfactants, aqueous dispersants, or polyurethane dispersants.

5. The modified bone cement according to claim 1, characterized in that, The mass ratio of the polycitric acid ester to the dispersant is 100:(0.1-5).

6. A method for preparing modified bone cement as described in any one of claims 1-5, characterized in that, The preparation method includes: (1) Polycitric acid ester, polyacrylate elastomer and dispersant are mixed to obtain nanospheres; (2) Mix the nanospheres obtained in step (1) with methacrylic acid monomers to obtain a premix; (3) The premix obtained in step (2) is mixed with polymethyl methacrylate and subjected to a curing reaction to obtain the modified bone cement.

7. The preparation method according to claim 6, characterized in that, The mixing in step (1) is carried out in the presence of an organic solvent.

8. The preparation method according to claim 7, characterized in that, The organic solvent includes any one or a combination of at least two of the following: dichloromethane, chloroform, acetone, butanone, ethyl acetate, butyl acetate, dimethylformamide, or dimethyl sulfoxide.

9. The preparation method according to claim 7, characterized in that, The preparation method of the nanospheres in step (1) specifically includes: mixing polycitric acid ester, polyacrylate elastomer and organic solvent for the first time to obtain a composite material solution, mixing the composite material solution with a dispersant for the second time, and dispersing, centrifuging and freeze-drying to obtain the nanospheres.

10. The preparation method according to claim 9, characterized in that, The dispersion time is 3-5 hours.

11. The preparation method according to claim 9, characterized in that, The centrifugation time is 5-30 minutes.

12. The preparation method according to claim 9, characterized in that, The centrifugation rate is 6000-20000 rpm.

13. The preparation method according to claim 9, characterized in that, The freeze-drying time is 3-10 h.

14. The preparation method according to claim 9, characterized in that, The freeze-drying temperature is -40 to -5°C.

15. The preparation method according to claim 6, characterized in that, The curing reaction temperature in step (3) is 25-90℃.

16. The preparation method according to claim 6, characterized in that, The curing reaction takes 5-15 minutes.

17. The use of the modified bone cement as described in any one of claims 1-5 in orthopedic bioactive materials.

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