Composite bone cement as well as preparation method and application thereof

Abstract

The invention relates to composite bone cement as well as a preparation method and application thereof. The composite bone cement comprises a solid-phase component and a liquid-phase component, the solid-phase component is prepared from a compound of poly (citric acid)-poloxamer F127-1, 8-octylene glycol ester and bioactive glass, a developing agent and polymethyl methacrylate. According to the composite bone cement provided by the invention, by introducing a compound (POFC / BG compound) of polycitric acid-poloxamer F127-1, 8-octylene glycol ester (POFC) and bioactive glass (BG), the technical effects of maintaining high strength of a PMMA matrix, reducing the elasticity modulus of PMMA and improving the osteogenic activity and degradation performance of the PMMA matrix are achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a composite bone cement and a preparation method and application thereof. Background Art

[0002] Bone tissue damage caused by various reasons, such as fractures and bone defects, has always been a common orthopedic problem. Bones have a high regenerative capacity, but it is not unlimited. When the bone defect exceeds the critical size, the bone cannot regenerate itself, and natural or synthetic bone graft materials are needed to support and guide bone regeneration cells. Polymethyl methacrylate (PMMA) bone cement has been used in orthopedic surgery for more than 50 years. It has the advantages of high strength, good plasticity and low cost. It is currently the most widely used bone cement material. However, there are also many disadvantages, including excessively high polymerization temperature, mismatch between the elastic modulus and human bone, volume shrinkage, etc., and PMMA is a bioinert material that lacks a porous structure and bone induction activity. Not only can it not be degraded, but bone tissue cannot grow into it.

[0003] In order to solve the problem of poor bioactivity of PMMA bone cement, some inorganic bioactive ingredients have been introduced, such as hydroxyapatite, calcium phosphate cement (CPC) or other bioceramics that release bioactive ions. The introduction of these inorganic bioactive ingredients is usually physical blending with PMMA powder, but after mixing with the liquid phase, most of the inorganic powder will be encapsulated in the flowing PMMA formed by the polymerization reaction. Due to the density, hydrophobicity and low porosity of PMMA, only a small amount of inorganic components on the surface can degrade and release bioactive ions. If the inorganic phase content is further increased (≥50%), it will lead to discontinuity of the PMMA matrix and disintegration in body fluids, resulting in a continuous decline in mechanical properties.

[0004] To prevent encapsulation of hydrophobic PMMA, some researchers have introduced hydrophilic calcium phosphate cement (CPC). However, the combination of organic and inorganic phases, and hydrophilic and hydrophobic phases, introduces new interfacial issues. The presence of gaps at the phase interface affects the overall mechanical strength and toughness of the composite bone cement, hindering its application in load-bearing areas and making it difficult to achieve the minimum compressive strength of cured bone cement of 70 MPa specified in ISO-5833-2002. Furthermore, CPC lacks osteoinductivity, has low mechanical strength, and a slow degradation rate, making it difficult to meet the needs of clinical use and bone regeneration.

[0005] Therefore, there is an urgent need to find a new modification method that can solve the problems of poor bioactivity and low mechanical properties of PMMA bone cement and provide an organic-inorganic composite bone cement with good comprehensive performance. Summary of the Invention

[0006] To address the above technical issues, the present invention provides a composite bone cement, its preparation method, and application. The composite bone cement provided by the present invention incorporates a composite of poly(citrate-poloxamer F127-1,8-octanediol) (POFC) and bioactive glass (BG) (POFC / BG composite). This composite bone cement maintains the high strength of the PMMA matrix, reduces the PMMA elastic modulus, and improves its osteogenic activity and degradation properties. This composite cement can stabilize fractured vertebrae during vertebroplasty and prevent further collapse.

[0007] To achieve this object, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a composite bone cement, comprising a solid phase component and a liquid phase component; the solid phase component comprises a composite of polycitrate-poloxamer F127-1,8-octanediol (POFC) and bioactive glass (BG) (POFC / BG composite), a developer, and polymethyl methacrylate (PMMA).

[0009] Bioactive glass (BG) has good bioactivity, osteoconductivity and osteoinduction, and has significant ability to promote bone regeneration. Poly (1,8-octanediol citrate) (POC) is a cross-linked bioelastomer with good cell compatibility, biodegradability, and mechanical properties matching those of soft tissue, but its hydrophilicity is poor. The hydration properties of biomaterials directly determine the mechanical stability, degradation rate, and diffusion characteristics under dynamic in vivo conditions. By introducing the amphiphilic copolymer poloxamer F127 (Pluronic F127) into POC, the resulting POFC elastomer has better hydrophilicity, mechanical properties, and blood compatibility. F127 has good properties such as non-toxicity, biocompatibility, and bioabsorbability, and has been approved by the FDA for clinical use. In addition, the citrate ions in POFC form coordination bonds with metal cations to form stable chelates.

[0010] To address the defects of PMMA bone cement, such as its high elastic modulus, poor osteogenic activity and inability to degrade, the present invention introduces the bioelastomer POFC and BG, which has good osteogenic activity and degradation properties, into the PMMA matrix of bone cement, thereby reducing the elastic modulus of PMMA while improving its osteogenic activity and degradation properties.

[0011] To address the current challenges of inorganic powder encapsulation and interfacial gaps in PMMA, the present invention coats the BG surface with amphiphilic POFC, forming a covalent bond between the POFC and the BG through chelation. Furthermore, the amphiphilic nature of POFC allows the POFC / BG composite to form a strong bond with the PMMA matrix through liquid-phase polymerization.

[0012] To address the problems of the PMMA matrix's compactness and hydrophobicity hindering the degradation and release of inorganic components in the core, and PMMA's low porosity hindering cell incorporation, the present invention introduces a large amount of POFC / BG composites, which form a connected network within the PMMA matrix. The POFC on the BG surface creates a water transport network, allowing the BG in the core to hydrate and release active ions, which are then released to the exterior of the composite bone cement through the POFC water transport network. Furthermore, the POFC / BG composite exhibits excellent degradation properties, allowing cells or new bone to gradually ingrow into the composite bone cement along the pores formed by the degradation of the POFC / BG, thereby forming a good bond with the host bone.

[0013] The present invention introduces the POFC / BG composite, thereby maintaining the high strength of the PMMA matrix and reducing the elastic modulus of PMMA, while achieving the technical effect of improving its osteogenic activity and degradation performance, and continuously releasing bioactive ions.

[0014] Preferably, the solid phase components include, by mass, 30-60 parts (for example, 30 parts, 35 parts, 40 parts, 45 parts, 50 parts, 55 parts, 60 parts, etc.) of a complex of polycitrate-poloxamer F127-1,8-octanediol and bioactive glass, 10-30 parts (for example, 10 parts, 15 parts, 20 parts, 25 parts, 30 parts, etc.) of a developer, and 20-60 parts (for example, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, 50 parts, 55 parts, 60 parts, etc.) of polymethyl methacrylate.

[0015] Preferably, the bioactive glass comprises strontium-doped bioactive glass.

[0016] Preferably, in the strontium-doped bioactive glass, the molar ratio of silicon to the total amount of calcium plus strontium is (1.3-2):1 (for example, it can be 1.3:1, 1.5:1, 1.7:1, 1.9:1, 2:1, etc.), and the molar ratio of calcium to strontium is (0.5-5):1 (for example, it can be 0.5:1, 1:1, 2:1, 3:1, 4:1, 5:1, etc.).

[0017] Preferably, the method for preparing the strontium-doped bioactive glass comprises the following steps:

[0018] Tetraethyl silicate, triethyl phosphate, a solvent and a catalyst are mixed to carry out a first reaction, and then calcium nitrate and strontium nitrate are added to carry out a second reaction. After gelation, freeze drying and sintering, strontium-doped bioactive glass is obtained.

[0019] Preferably, the solvent comprises ethanol and / or water.

[0020] Preferably, the catalyst comprises dilute hydrochloric acid.

[0021] Preferably, the concentration of the dilute hydrochloric acid is 0.3-0.6 mol / L (for example, 0.3 mol / L, 0.4 mol / L, 0.5 mol / L, 0.6 mol / L, etc.).

[0022] Preferably, the usage ratio of tetraethyl silicate, triethyl phosphate, solvent, catalyst, calcium nitrate and strontium nitrate is (8-12) mL: (0.8-1.3) mL: (12-20) mL: (0.12-0.24) mmol: (1-5) g: (1-5) g.

[0023] The above-mentioned value (8-12) mL can be, for example, 8 mL, 9 mL, 10 mL, 11 mL, 12 mL, etc.; (0.8-1.3) mL can be, for example, 0.8 mL, 0.9 mL, 1 mL, 1.1 mL, 1.2 mL, 1.3 mL, etc.; (12-20) mL can be, for example, 12 mL, 16 mL, 18 mL, 20 mL, etc.; (0.12-0.24) mmol can be, for example, 0.12 mmol, 0.16 mmol, 0.2 mmol, 0.24 mmol, etc.; (1-5) g can be, for example, 1 g, 2 g, 3 g, 4 g, 5 g, etc.

[0024] Preferably, the molar ratio of calcium nitrate to strontium nitrate is (0.5-5):1 (for example, it can be 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, etc.).

[0025] Preferably, the time for the first reaction and the second reaction is independently 30-60 min (for example, 30 min, 40 min, 50 min, 60 min, etc.)

[0026] Preferably, the gelation temperature is 30-80°C (for example, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, etc.), and the gelation time is 0.5-3 days (for example, 0.5 day, 1 day, 2 days, 3 days, etc.).

[0027] Preferably, the sintering further includes grinding and screening operations.

[0028] Preferably, in the composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass, the mass ratio of polycitrate-poloxamer F127-1,8-octanediol ester to bioactive glass is 1:(0.5-2) (for example, it can be 1:0.5, 1:1, 1:1.5, 1:2, etc.).

[0029] Preferably, the preparation method of the composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass comprises the following steps:

[0030] (1) mixing polycitrate-poloxamer F127-1,8-octanediol ester and a solvent to obtain component one; and mixing bioactive glass and a solvent to obtain component two;

[0031] (2) Component one and component two are mixed, and after freeze-drying and solidification, a composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass is obtained.

[0032] Preferably, the solvents in step (1) independently include any one of ethanol, methanol or water, or a combination of at least two of them.

[0033] Preferably, the concentration of polycitrate-poloxamer F127-1,8-octanediol ester in the component 1 of step (1) is 20-60 wt% (for example, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, etc.).

[0034] Preferably, the concentration of the bioactive glass in the second component of step (1) is 10-40 wt% (for example, 10 wt%, 20 wt%, 30 wt%, 40 wt%, etc.).

[0035] Preferably, step (2) further includes ultrasonic treatment after the mixing.

[0036] Preferably, the curing in step (2) comprises curing under vacuum at 75-85°C (for example, 75°C, 78°C, 80°C, 82°C, 85°C, etc.) for 2-4 days (for example, 2 days, 3 days, 4 days, etc.).

[0037] Preferably, step (2) further includes crushing and grinding after solidification.

[0038] Preferably, the preparation method of the polycitrate-poloxamer F127-1,8-octanediol ester comprises the following steps: mixing citric acid, 1,8-octanediol and poloxamer F127, heating and melting, and then dialyzing to obtain the polycitrate-poloxamer F127-1,8-octanediol ester.

[0039] Preferably, the molar ratio of citric acid to 1,8-octanediol is 1:(0.7-1.3) (for example, it can be 1:0.7, 1:0.9, 1:1.1, 1:1.3, etc.).

[0040] Preferably, the amount of Poloxamer F127 is 5-30 wt% (eg, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, etc.) of the total amount of citric acid and 1,8-octanediol.

[0041] Preferably, the heating and melting temperature is 140-180°C (for example, 140°C, 145°C, 150°C, 155°C, 160°C, 170°C, 180°C, etc.), and the time is 1.5-4h (for example, 1.5h, 2h, 2.5h, 3h, 4h, etc.).

[0042] Preferably, the developer comprises zirconium oxide and / or barium sulfate.

[0043] Preferably, the liquid phase components include methyl methacrylate (MMA) and a curing accelerator.

[0044] Preferably, the liquid phase components include 95-99 parts (for example, 95 parts, 96 parts, 97 parts, 98 parts, 99 parts, etc.) of methyl methacrylate and 1-5 parts (for example, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, etc.) of curing accelerator in parts by mass.

[0045] Preferably, the curing accelerator includes N,N-dimethyl-p-toluidine.

[0046] Preferably, the usage ratio of the solid phase component and the liquid phase component is (1-3) g:1 mL (for example, it can be 1 g:1 mL, 1.5 g:1 mL, 2 g:1 mL, 2.5 g:1 mL, 3 g:1 mL, etc.).

[0047] In a second aspect, the present invention provides a method for preparing the composite bone cement according to the first aspect, the preparation method comprising: mixing and stirring a solid phase component and a liquid phase component, and then solidifying to obtain the composite bone cement.

[0048] In a second aspect, the present invention provides a use of the composite bone cement according to the first aspect in preparing a bone transplant material.

[0049] Compared with the prior art, the present invention has at least the following beneficial effects:

[0050] (1) The present invention improves the osteogenic activity and degradation performance of PMMA while maintaining the high strength of the PMMA matrix and reducing the elastic modulus of PMMA by introducing the bioelastomer POFC and BG with good osteogenic activity and degradation performance.

[0051] (2) The present invention forms a firmly bonded POFC / BG composite by coating POFC on the surface of BG. The amphiphilic property of POFC enables it to act as an intermediate to tightly combine the organic PMMA matrix and the inorganic phase BG, eliminating the organic-inorganic interface and improving the mechanical strength of the organic-inorganic composite bone cement.

[0052] (3) The present invention introduces a POFC / BG complex, which forms a connected network in bone cement. The water transport network formed by POFC is used to achieve the degradation of the core BG and the release of bioactive ions. At the same time, the pores left by the degradation of the POFC / BG complex are conducive to the growth of cells and new bone, thereby forming a good bond with the host bone. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 It is a schematic structural diagram of the bone cement provided by the present invention. DETAILED DESCRIPTION

[0054] The technical solution of the present invention will be further described below with reference to the accompanying drawings and through specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0055] Preparation Example 1-1

[0056] This preparation example provides a method for preparing POFC using a melt process: under a nitrogen atmosphere, citric acid, 1,8-octanediol, and Pluronic F127 are added to a three-necked flask, wherein the molar ratio of citric acid to 1,8-octanediol is 1:0.9, and Pluronic F127 accounts for 10 wt % of the total amount of citric acid and 1,8-octanediol. The mixture is placed in an oil bath at 140°C with vigorous stirring. After the reactants are melted, stirring is maintained at 120°C for 1 hour, and dialyzed for 3 days to obtain a POFC prepolymer.

[0057] Preparation Example 1-2

[0058] This preparation example provides a method for preparing POFC using a melt process: under a nitrogen atmosphere, citric acid, 1,8-octanediol, and Pluronic F127 are added to a three-necked flask, wherein the molar ratio of citric acid to 1,8-octanediol is 1:1.1, and Pluronic F127 accounts for 20 wt % of the total amount of citric acid and 1,8-octanediol. The mixture is placed in an oil bath at 160°C with vigorous stirring. After the reactants are melted, stirring is maintained at 140°C for 2 hours, and dialyzed for 3 days to obtain a POFC prepolymer.

[0059] Preparation Examples 1-3

[0060] This preparation example provides a method for preparing POFC using a melt process: under a nitrogen atmosphere, citric acid, 1,8-octanediol, and Pluronic F127 are added to a three-necked flask, wherein the molar ratio of citric acid to 1,8-octanediol is 1:1.3, and Pluronic F127 accounts for 30 wt% of the total amount of citric acid and 1,8-octanediol. The flask is heated in an oil bath at 180°C with vigorous stirring. After the reactants are melted, stirring is maintained at 160°C for 3 hours, and the POFC prepolymer is obtained after dialysis for 3 days.

[0061] Preparation Example 2-1

[0062] This preparation example provides a method for preparing BG using a gel-sol method: 8 mL of tetraethyl silicate, 1.3 mL of triethyl phosphate, 6 mL of ethanol, and 10 mL of purified water are added to a three-necked flask in sequence, and 0.4 mL of a 0.3 mol / L dilute hydrochloric acid solution is added dropwise. After reacting for 30 minutes, 5 g (0.021 mol) of calcium nitrate tetrahydrate and 1 g (0.005 mol) of strontium nitrate are added, and the mixture is reacted for 30 minutes. The mixture is gelled at 40°C for 1 day, freeze-dried, sintered, ground, and sieved to obtain white BG powder. The molar ratio of silicon to (calcium + strontium) in the obtained BG is 1.4:1, and the molar ratio of calcium to strontium is 4.5:1.

[0063] Preparation Example 2-2

[0064] This preparation example provides a method for preparing BG using a gel-sol method: 9 mL of tetraethyl silicate, 1.2 mL of triethyl phosphate, 7 mL of ethanol, and 9 mL of purified water are added to a three-necked flask in sequence, and 0.5 mL of a 0.3 mol / L dilute hydrochloric acid solution is added dropwise. After reacting for 40 minutes, 4 g (0.017 mol) of calcium nitrate tetrahydrate and 2 g (0.009 mol) of strontium nitrate are added, and the mixture is reacted for 40 minutes. The mixture is gelled at 50°C for 2 days, freeze-dried, sintered, ground, and sieved to obtain white BG powder. The molar ratio of silicon to (calcium + strontium) in the obtained BG is 1.5:1, and the molar ratio of calcium to strontium is 1.8:1.

[0065] Preparation Example 2-3

[0066] This preparation example provides a method for preparing BG using a gel-sol method: 10 mL of tetraethyl silicate, 1.1 mL of triethyl phosphate, 8 mL of ethanol, and 8 mL of purified water are added to a three-necked flask in sequence, and 0.6 mL of a 0.3 mol / L dilute hydrochloric acid solution is added dropwise. After reacting for 50 minutes, 3 g (0.013 mol) of calcium nitrate tetrahydrate and 3 g (0.014 mol) of strontium nitrate are added, and the mixture is reacted for 50 minutes. The mixture is gelled at 60°C for 3 days, freeze-dried, sintered, ground, and sieved to obtain white BG powder. The molar ratio of silicon to (calcium + strontium) in the obtained BG is 1.7:1, and the molar ratio of calcium to strontium is 0.9:1.

[0067] Preparation Example 3-1

[0068] This preparation example provides a method for preparing a POFC / BG composite: POFC (Preparation Example 1-1) is dissolved in ethanol to obtain component one at a concentration of 20 wt%; BG powder (Preparation Example 2-1) is ultrasonically dispersed in ethanol to obtain component two at a concentration of 40 wt%; component one and component two are mixed in a mass ratio of 1:1, ultrasonically mixed for 1 hour, freeze-dried, cured at 80°C for 3 days, and then crushed and ground to 300-500 μm. The mass ratio of POFC to BG in the resulting composite is 1:2.

[0069] Preparation Example 3-2

[0070] This preparation example provides a method for preparing a POFC / BG composite: POFC (Preparation Example 1-2) is dissolved in ethanol to obtain component one at a concentration of 30 wt%; BG powder (Preparation Example 2-2) is ultrasonically dispersed in ethanol to obtain component two at a concentration of 30 wt%; component one and component two are mixed in a mass ratio of 1:1, ultrasonically mixed for 1 hour, freeze-dried, cured at 80°C for 3 days, and then crushed and ground to 300-500 μm. The mass ratio of POFC to BG in the resulting composite is 1:1.

[0071] Preparation Example 3-3

[0072] This preparation example provides a method for preparing a POFC / BG composite: POFC (Preparation Examples 1-3) is dissolved in ethanol to obtain component one at a concentration of 40 wt%; BG powder (Preparation Examples 2-3) is ultrasonically dispersed in ethanol to obtain component two at a concentration of 20 wt%; component one and component two are mixed in a mass ratio of 1:1, ultrasonically mixed for 1 hour, freeze-dried, cured at 80°C for 3 days, and then crushed and ground to 300-500 μm. The mass ratio of POFC to BG in the resulting composite is 1:0.5.

[0073] Example 1

[0074] This embodiment provides a composite bone cement, comprising a solid phase component and a liquid phase component;

[0075] The solid phase components include, by weight, 40 parts of the POFC / BG composite (Preparation Example 3-1), 10 parts of a developer (zirconium oxide: barium sulfate = 2:1, mass ratio), and 50 parts of PMMA powder; the liquid phase components include, by weight, 97 parts of MMA and 3 parts of N,N-dimethyl-p-toluidine;

[0076] The content ratio of the solid phase component to the liquid phase component is 2.5 g:1 mL.

[0077] The preparation method of the composite bone cement comprises: mixing and stirring a solid phase component and a liquid phase component for 3 minutes, injecting the mixture into a mold and solidifying the mixture to obtain the composite bone cement.

[0078] Schematic diagram of the structure of bone cement Figure 1 shown.

[0079] Example 2

[0080] This embodiment provides a composite bone cement, comprising a solid phase component and a liquid phase component;

[0081] The solid phase components include, by weight, 50 parts of the POFC / BG composite (Preparation Example 3-1), 15 parts of a developer (zirconium oxide: barium sulfate = 1:1, mass ratio), and 35 parts of PMMA powder; the liquid phase components include, by weight, 98 parts of MMA and 2 parts of N,N-dimethyl-p-toluidine;

[0082] The content ratio of the solid phase component to the liquid phase component is 2g:1mL.

[0083] The preparation method of the composite bone cement is as described in Example 1.

[0084] Example 3

[0085] This embodiment provides a composite bone cement, comprising a solid phase component and a liquid phase component;

[0086] The solid phase components include, by weight, 60 parts of the POFC / BG composite (Preparation Example 3-1), 20 parts of a developer (zirconium oxide: barium sulfate = 1:2, mass ratio), and 20 parts of PMMA powder; the liquid phase components include, by weight, 99 parts of MMA and 1 part of N,N-dimethyl-p-toluidine;

[0087] The content ratio of the solid phase component to the liquid phase component is 1.5 g:1 mL.

[0088] The preparation method of the composite bone cement is as described in Example 1.

[0089] Example 4

[0090] This embodiment provides a composite bone cement, which differs from Example 1 only in that the POFC / BG composite provided in Preparation Example 3-1 is replaced by the POFC / BG composite provided in Preparation Example 3-2 in equal amounts. Other details refer to Example 1.

[0091] Example 5

[0092] This embodiment provides a composite bone cement, which differs from Example 1 only in that an equal amount of the POFC / BG composite provided in Preparation Example 3-1 is replaced by the POFC / BG composite provided in Preparation Example 3-3. Other details refer to Example 1.

[0093] Comparative Example 1

[0094] This comparative example provides a PMMA bone cement, which differs from Example 1 only in that the solid phase component does not contain POFC / BG composite. Other details refer to Example 1.

[0095] Comparative Example 2

[0096] This comparative example provides a composite bone cement, which differs from Example 1 only in that an equal amount of POFC / BG composite is replaced with 40 parts of BG in the solid phase component (Preparation Example 2-1). Other details refer to Example 1.

[0097] Comparative Example 3

[0098] This comparative example provides a composite bone cement, which differs from Example 1 only in that the POFC / BG composite is replaced with uncompounded POFC (Preparation Example 1-1) and BG (Preparation Example 2-1) in the solid phase component, while the amount and ratio of POFC and BG remain unchanged. For other reasons, refer to Example 1.

[0099] Test Example 1

[0100] Compression performance test

[0101] Test method:

[0102] The test method follows ISO-5833-2002: Bone cement samples (Φ6 × 12 mm) are placed in a universal testing machine and subjected to compressive strength testing at a loading rate of 20 mm / min. The elastic modulus is calculated from the first derivative of the stress-strain curve. At least five samples are measured per group and the average value is calculated.

[0103] The compressive strength and elastic modulus of the bone cement products of Examples 1-5 and Comparative Examples 1-3 are shown in Table 1.

[0104] Table 1

[0105] Grouping Compressive strength (MPa) Elastic modulus (MPa) Example 1 90.49±2.34 1418.07±25.49 Example 2 78.13±1.74 1204.36±53.0 Example 3 70.92±3.48 1061.33±30.30 Example 4 91.57±3.15 1538.56±46.25 Example 5 89.57±2.69 1486.57±35.47 Comparative Example 1 120.96±6.07 2269.27±73.00 Comparative Example 2 69.47±3.47 1647.57±45.24 Comparative Example 3 73.57±4.25 1534.24±54.34

[0106] Test results:

[0107] (1) It can be seen from Examples 1 to 5 that the composite bone cement provided by the present invention still has a relatively high compressive strength (greater than 70 MPa specified in ISO-5833-2002), and the introduced POFC / BG composite can be well bonded to the PMMA matrix, reducing the elastic modulus of the bone cement, making it more compatible with human bone. Specifically, the compressive strength is 70.92-91.57 MPa, and the elastic modulus is 1061.33-1538.56 MPa.

[0108] (2) By comparing Example 1 with Comparative Examples 1-3, it can be seen that when the POFC / BG composite is missing in the bone cement, the elastic modulus is high and cannot match human bone; and when the BG in the bone cement lacks the POFC composite, the gap at the organic-inorganic interface between the BG and the PMMA matrix causes the strength of the composite bone cement to decrease.

[0109] Test Example 2

[0110] Degradation performance test

[0111] Test method:

[0112] In vitro degradation experiments were conducted according to GB / T 16886. The specific steps were as follows: a fully solidified composite bone cement sample was weighed using a precision balance. The composite bone cement was then immersed in a 10-mL centrifuge tube containing PBS at a ratio of 0.2 g / mL. The tube was then placed in a constant temperature and humidity chamber at 37°C and 100% humidity. The samples were removed after drying and weighing at 7 and 28 days. The degradation performance of the composite bone cement was evaluated by mass loss.

[0113] The degradation performance test results of Examples 1-5 and Comparative Examples 1-3 are shown in Table 2.

[0114] Table 2

[0115]

[0116]

[0117] Test results show that the degradation rate of the composite bone cement provided by the present invention gradually increases with immersion time in simulated body fluids, and the overall degradation rate of the composite bone cement increases with increasing POFC / BG content. In Comparative Example 1, only a small amount of the developer not encapsulated by PMMA degraded, with virtually no degradation occurring. In Comparative Example 2, the lack of a water transport network formed by the POFC prevented degradation of the core BG, resulting in a lower degradation rate. In Comparative Example 3, the BG portion lacking the POFC coating was encapsulated by the PMMA matrix, making it less susceptible to degradation in contact with body fluids.

[0118] Test Example 3

[0119] Ion release concentration test

[0120] Test method:

[0121] The composite bone cement samples were immersed in PBS solution at a solid-liquid ratio of 0.2 g / mL. The concentrations of calcium ions and strontium ions released from the composite bone cement in the immersion solution were tested using an ICP spectrometer at 7 and 28 days.

[0122] The ion release concentration test results of Examples 1-5 and Comparative Examples 2-3 are shown in Table 3.

[0123] Table 3

[0124]

[0125]

[0126] Test results indicate that the composite bone cement provided by the present invention gradually releases calcium and strontium ions with increasing immersion time. The released concentrations of calcium and strontium ions are positively correlated with the POFC / BG content and the calcium / strontium content of the BG. This suggests that the interconnected network formed by the POFC / BG composite enables the BG to hydrate with body fluids, degrade, and release bioactive ions. In contrast, the lack of a water transport network formed by the POFC in Comparative Example 2 hinders hydration of the core BG with body fluids, resulting in lower ion release concentrations. While the POFC-formed water transport network exists in Comparative Example 3, the BG portion lacking the POFC coating is encapsulated by the PMMA matrix, preventing hydration and degradation to release bioactive ions.

[0127] The applicant declares that the above is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention fall within the scope of protection and disclosure of the present invention.

Claims

1. A composite bone cement, characterized in that: The composite bone cement comprises a solid phase component and a liquid phase component; the solid phase component comprises a composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass, a developer and polymethyl methacrylate.

2. The composite bone cement according to claim 1, characterized in that The solid phase components include, by mass, 30-60 parts of a complex of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass, 10-30 parts of a developer, and 20-60 parts of polymethyl methacrylate.

3. The composite bone cement according to claim 1 or 2, characterized in that The bioactive glass includes strontium-doped bioactive glass; Preferably, in the strontium-doped bioactive glass, the molar ratio of silicon to the total amount of calcium plus strontium is (1.3-2):1, and the molar ratio of calcium to strontium is (0.5-5):

1.

4. The composite bone cement according to any one of claims 1 to 3, characterized in that In the composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass, the mass ratio of polycitrate-poloxamer F127-1,8-octanediol ester to bioactive glass is 1:(0.5-2).

5. The composite bone cement according to any one of claims 1 to 4, characterized in that The preparation method of the composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass comprises the following steps: (1) mixing polycitrate-poloxamer F127-1,8-octanediol ester and a solvent to obtain component one; and mixing bioactive glass and a solvent to obtain component two; (2) Component one and component two are mixed, and after freeze-drying and solidification, a composite of polycitrate-poloxamer F127-1,8-octanediol ester and bioactive glass is obtained.

6. The composite bone cement according to claim 5, characterized in that The solvents in step (1) each independently include any one of ethanol, methanol or water, or a combination of at least two thereof; Preferably, the concentration of polycitrate-poloxamer F127-1,8-octanediol ester in the component 1 of step (1) is 20-60 wt %; Preferably, the concentration of the bioactive glass in the second component in step (1) is 10-40 wt%.

7. The composite bone cement according to any one of claims 1 to 6, characterized in that The developer includes zirconium oxide and / or barium sulfate.

8. The composite bone cement according to any one of claims 1 to 7, characterized in that: The liquid phase components include methyl methacrylate and a curing accelerator; Preferably, the liquid phase component comprises 95-99 parts by mass of methyl methacrylate and 1-5 parts by mass of a curing accelerator; Preferably, the curing accelerator includes N,N-dimethyl-p-toluidine; Preferably, the usage ratio of the solid phase component to the liquid phase component is (1-3) g:1 mL.

9. A method for preparing the composite bone cement according to any one of claims 1 to 8, characterized in that: The preparation method comprises: mixing and stirring the solid phase component and the liquid phase component, and then solidifying to obtain the composite bone cement.

10. Use of the composite bone cement according to any one of claims 1 to 8 in preparing bone transplant materials.

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