Low-melting alloy / temperature-sensitive hydrogel composite bone cement and method for preparing the same

Abstract

The application discloses a low-melting-point alloy / temperature-sensitive hydrogel composite bone cement and a preparation method thereof. The temperature-sensitive hydrogel is wrapped outside the low-melting-point alloy, the liquid temperature-sensitive hydrogel can absorb the heat released by the low-melting-point alloy during solidification and is converted into a gel state, and the low-melting-point alloy is rapidly cooled after being wrapped by the temperature-sensitive hydrogel and is not in direct contact with the surrounding bone tissue, so that the low-melting-point alloy avoids causing thermal damage to the surrounding tissue, reduces the pain of patients, promotes the rapid healing of the affected area, and the composite bone cement also has the advantages of fast solidification speed, simple preparation process, stable structure in the in-vivo and in-vitro environments and the like.

Description

Technical Field

[0001] This invention relates to the field of bone defect repair technology. More specifically, it relates to a low-melting-point alloy / thermosensitive hydrogel composite bone cement and its preparation method. Background Technology

[0002] Bone defects are a common orthopedic condition, primarily caused by bone tumors, bone trauma, and congenital diseases. Bone cement can be used to fill and repair these defects. Currently, commonly used bone cements include polymethyl methacrylate (PMMA) cement and calcium phosphate (CPC) cement. PMMA cement has good plasticity and mechanical properties, but poor biocompatibility and long-term use in the body can lead to diffusion and inflammation in surrounding tissues. CPC cement has better biocompatibility, but lower mechanical strength and shorter lifespan. In addition, hydrogels are also a commonly used material for filling bone defects in current research. Hydrogels have good biocompatibility and are biodegradable, but their mechanical properties are relatively poor.

[0003] Low-melting-point alloys have good plasticity, high mechanical strength, fast curing speed, and radioactivity, so they can also be used as bone cement to fill bone damage. However, the melting point of low-melting-point alloy bone cements used in current research is generally above 60°C. When injected at this temperature, the high temperature will damage the surrounding bone tissue, making the wound difficult to heal. In severe cases, it may cause infection of surrounding tissues and increase the patient's pain. Therefore, there is a need to provide a new type of composite bone cement material to reduce the thermal damage during the injection of low-melting-point alloy bone cement. Summary of the Invention

[0004] In view of the above-mentioned shortcomings, one object of the present invention is to provide a low-melting-point alloy / thermosensitive hydrogel composite bone cement. The composite bone cement provided by the present invention is injectable, has a fast curing speed, a simple preparation process, stable structure in both in vivo and in vitro environments, and causes less thermal damage to surrounding bone tissue.

[0005] Another object of the present invention is to provide a method for preparing the low melting point alloy / thermosensitive hydrogel composite bone cement as described above.

[0006] To achieve the first objective mentioned above, the present invention adopts the following technical solution:

[0007] This invention discloses a low-melting-point alloy / thermosensitive hydrogel composite bone cement, wherein the thermosensitive hydrogel is wrapped around the outside of the low-melting-point alloy, and the mass-volume ratio of the low-melting-point alloy to the thermosensitive hydrogel is 1-3g:1ml.

[0008] Furthermore, the melting point of the low-melting-point alloy is 45-100℃. Preferably, the focus is on heat damage protection for low-melting-point alloys with melting points of 60-100℃. The low-melting-point alloy is commonly selected from one or more of gallium-indium alloy, gallium-indium-tin alloy, gallium-indium-tin-zinc alloy, gallium-tin alloy, indium-tin alloy, bismuth-indium alloy, bismuth-tin alloy, bismuth-indium-tin alloy, and bismuth-indium-tin-zinc alloy.

[0009] In one specific embodiment, when the low-melting-point alloy is a bismuth-indium-tin alloy, its raw material formulation is 32.5 wt% bismuth, 51 wt% indium and 16.5 wt% tin; or 54 wt% bismuth, 29.7 wt% indium and 16.3 wt% tin; or 31.6 wt% bismuth, 48.8 wt% indium and 19.6 wt% tin; or 43.2 wt% bismuth, 39.3 wt% indium and 17.5 wt% tin; preferably, when the low-melting-point alloy is a bismuth-indium-tin-zinc alloy, its raw material formulation is 35 wt% bismuth, 48.6 wt% indium, 16 wt% tin and 0.4 wt% zinc.

[0010] Furthermore, the glass transition temperature of the thermosensitive hydrogel is 35-37℃; the thermosensitive hydrogel is liquid at room temperature and gel-like within the body temperature range. When repairing bone defects, the thermosensitive hydrogel is first injected into the target area, followed by the injection of a low-melting-point alloy into the hydrogel. This prevents the low-melting-point alloy from directly contacting the surrounding bone tissue, and the significant temperature difference causes the alloy to solidify rapidly. The released heat is quickly absorbed by the surrounding thermosensitive hydrogel, transforming it into a gel state, reducing thermal damage to the surrounding bone tissue, providing thermal insulation, and improving its biocompatibility. Preferably, the thermosensitive hydrogel comprises poloxamer, hydroxypropyl methylcellulose, and deionized water; preferably, the thermosensitive hydrogel comprises 20 wt% poloxamer, 2.5 wt% hydroxypropyl methylcellulose, and 77.5 wt% deionized water.

[0011] To achieve the second objective mentioned above, the present invention adopts the following technical solution:

[0012] This invention discloses a method for preparing the low-melting-point alloy / thermosensitive hydrogel composite bone cement as described above, comprising the following steps:

[0013] 1) Preparation of thermosensitive hydrogel:

[0014] Weigh poloxamer, hydroxypropyl methylcellulose and deionized water in proportion and place them in a beaker. Place the beaker in an insulated container filled with ice and stir until completely mixed. Then place the mixture in a refrigerator at 0-4℃ for 24-36 hours to obtain a thermosensitive hydrogel.

[0015] 2) Preparation of low-melting-point alloys:

[0016] Place a beaker containing metal materials of a predetermined ratio in a vacuum drying oven and heat it. Set the heating temperature to 140-160℃ and the duration to 2-4 hours. Then stir the molten metal mixture for 3-5 hours to obtain a uniform low-melting-point alloy material.

[0017] 3) Preparation of composite bone cement:

[0018] The low-melting-point alloy material is drawn into the first syringe sleeve using an injection device, keeping the low-melting-point alloy in a liquid state. Then, the temperature-sensitive hydrogel is drawn into the second syringe sleeve using the injection device. The valve of the injection device is then controlled to inject the temperature-sensitive hydrogel into the target area first, and then the molten low-melting-point alloy material is rapidly injected into the temperature-sensitive hydrogel in the target area. After pressure treatment, it is solidified and molded into a support with a controllable structure.

[0019] In one specific embodiment, the injection device is a self-developed dedicated injection device that can achieve the effect of injecting low-melting-point alloy and temperature-sensitive hydrogel into the target area and solidifying them. The injection device has a Y-shaped structure, which includes three branches. Two of the branches are the first syringe sleeve and the second injection sleeve, and the third branch is the injection outlet. The first syringe sleeve is used to store the aspirated low-melting-point alloy material, and the second injection sleeve is used to store the aspirated temperature-sensitive hydrogel.

[0020] The injection device is also equipped with a three-way valve at the intersection of the three branches. The three-way valve is used to control the connection between the first injection sleeve or the second injection sleeve and the injection outlet. That is, when the first injection sleeve is connected to the injection outlet, the second injection sleeve is closed to the injection outlet to realize the injection of low melting point alloy material, or when the second injection sleeve is connected to the injection outlet, the first injection sleeve is closed to the injection outlet to realize the injection of temperature-sensitive hydrogel.

[0021] The first syringe sleeve and the second injection sleeve are each provided with a syringe plunger.

[0022] Furthermore, since the two materials have a large temperature difference, a heat insulation layer is provided on the outside of the first syringe sleeve and the second injection sleeve. In addition, in order to prevent the low melting point alloy from solidifying due to the temperature drop, a local heating device, such as a heating wire, is provided on the outside of the first syringe sleeve to heat the internal alloy.

[0023] Furthermore, the support body is a solid structure, a hollow structure, or a microporous structure.

[0024] Furthermore, the pressurization process is performed during the injection process, and the pressurization method is either gas pressurization or mechanical pressurization.

[0025] The beneficial effects of this invention are as follows:

[0026] This invention discloses a low-melting-point alloy / thermosensitive hydrogel composite bone cement and its preparation method. The thermosensitive hydrogel is wrapped around the low-melting-point alloy. The liquid thermosensitive hydrogel can absorb the heat released by the solidification of the low-melting-point alloy and transform into a gel state. After being wrapped by the thermosensitive hydrogel, the low-melting-point alloy cools down rapidly and does not come into direct contact with the surrounding bone tissue, thereby avoiding thermal damage to the surrounding tissue, reducing patient pain, and promoting rapid healing of the affected area. Furthermore, this composite bone cement also has the advantages of fast curing speed, simple preparation process, and structural stability in in vivo and in vitro environments. Attached Figure Description

[0027] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0028] Figure 1 This invention illustrates the dedicated injection device.

[0029] The components include: 1. syringe plunger; 2. insulation layer; 3. second injection sleeve; 4. injection outlet; 5. first syringe sleeve; 6. local heating device; and 7. three-way valve.

[0030] Figure 2 The curve showing the temperature change of the surrounding tissues when the composite bone cement of Example 2 was injected into the pig femur is shown.

[0031] Figure 3 The results of in vitro cell biocompatibility tests of low-melting-point alloys and thermosensitive hydrogels are shown: (a): cell viability of MC3T3-E1 cells cultured in BiInSn alloy extract for 3 and 7 days; (b): cell viability of MC3T3-E1 cells cultured in thermosensitive hydrogel extract for 1, 3, and 5 days; (c) fluorescent staining images of live / dead cells of MC3T3-E1 cells cultured in culture dishes, BiInSn alloy, and GaIn alloy for 3, 5, and 7 days.

[0032] Figure 4 The curves showing the temperature changes of the surrounding tissues when low-melting-point alloy bone cement was directly injected into the pig femur in Comparative Example 4 are shown. Detailed Implementation

[0033] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further clarifies the invention. It should be understood that the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0034] In one specific embodiment, the present invention provides a dedicated injection device for injecting low-melting-point alloy / thermosensitive hydrogel composite bone cement. The injection device has a Y-shaped structure design, which includes three branches, two of which are the first syringe sleeve 5 and the second injection sleeve 3, and the third branch is the injection outlet 4. The first syringe sleeve 5 is used to store the aspirated low-melting-point alloy material, and the second injection sleeve 3 is used to store the aspirated thermosensitive hydrogel.

[0035] The injection device is also equipped with a three-way valve 7 at the intersection of the three branches. The three-way valve 7 is used to control the connection between the first syringe sleeve 5 or the second syringe sleeve 3 and the injection outlet 4. That is, when the first syringe sleeve 5 is connected to the injection outlet 4, the second syringe sleeve 3 is closed to the injection outlet 4 to realize the injection of low melting point alloy material, or when the second syringe sleeve 3 is connected to the injection outlet 4, the first syringe sleeve 5 is closed to the injection outlet 4 to realize the injection of temperature-sensitive hydrogel.

[0036] The first syringe sleeve 5 and the second injection sleeve 3 are also provided with syringe plungers 1.

[0037] Furthermore, since the two materials have a large temperature difference, a heat insulation layer 2 is provided on the outside of the first syringe sleeve 5 and the second injection sleeve 3. In order to prevent the low melting point alloy from solidifying due to the temperature drop, a local heating device 6 is also provided on the outside of the first syringe sleeve 5, such as a heating wire, to heat the internal alloy.

[0038] Furthermore, the pressurization process is performed during the injection process, and the pressurization method is either gas pressurization or mechanical pressurization.

[0039] Example 1

[0040] Preparation of low-melting-point alloy: Bismuth (Bi), indium (In), and tin (Sn) were mixed in an empty beaker at mass fractions of 32.5%, 51%, and 16.5%, respectively. The beaker was placed in a vacuum drying oven and heated at 150°C for 3 hours. After melting, the mixture was stirred thoroughly in a magnetic water bath for 4 hours to obtain a low-melting-point alloy material with a melting point of 60°C.

[0041] Preparation of thermosensitive hydrogel: Poloxamer (F127), hydroxypropyl methylcellulose (HPMC), and deionized water were weighed at 20%, 2.5%, and 77.5% by mass and placed in beakers. The beakers were placed in an insulated container filled with ice and stirred with a glass rod until the mixture became liquid and had good fluidity. Then, the beakers were placed in a refrigerator at 4°C to allow the thermosensitive hydrogel to fully swell. A portion of the thermosensitive hydrogel was taken and placed in a 3ml test tube. The tubes were placed in water baths at room temperature (21°C) and 37°C, and the tubes were inverted at 2 min, 8 min, 15 min, 25 min, and 35 min to observe whether the hydrogel had transformed into a gel. The results showed that the thermosensitive hydrogel prepared in this ratio remained liquid for 35 min at room temperature (21°C), but transformed into a gel in 2 seconds in a water bath at 37°C.

[0042] Example 2

[0043] A hole with a diameter of 8 cm and a depth of 10 cm was drilled in the pig femur using an electric drill to simulate a bone defect. The femur was then placed in a 37°C water bath. The low-melting-point alloy material prepared in Example 1 was drawn into the first syringe sleeve using an injection device, keeping the alloy in a liquid state. The thermosensitive hydrogel prepared in Example 1 was then drawn into the second syringe sleeve using the same device. The three-way valve of the injection device was controlled to inject the thermosensitive hydrogel into the target area first, and the temperature change of the bone tissue around the hole was recorded. Then, the molten low-melting-point alloy material was rapidly injected into the thermosensitive hydrogel in the target area. After pressure treatment, the material solidified into a structurally controllable support. The mass-to-volume ratio of the low-melting-point alloy to the thermosensitive hydrogel was 3 g:1 ml. The temperature change curve of the surrounding tissue is shown in the figure. Figure 2 When the thermosensitive hydrogel is injected, the temperature of the surrounding tissue drops slightly, with the lowest temperature at the injection center dropping to 25.6℃. As the low-melting-point alloy material is injected, the temperature of the surrounding tissue rises rapidly, with the highest temperature at the injection center reaching 33.45℃. This indicates that this method can effectively prevent thermal damage to the surrounding bone tissue during the injection of the low-melting-point alloy.

[0044] Example 3

[0045] To evaluate the proliferation of MC3T3-E1 cells on the aforementioned BiInSn-thermosensitive hydrogel composite bone cement, biocompatibility was assessed. Cell viability was determined using the CCK-8 assay according to ISO 10993-12. The ratio of low-melting-point alloy BiInSn sheet to culture medium was 3 cm². 2 The thermosensitive hydrogel was soaked in culture medium at a ratio of 0.1 g / ml for 48 hours, and the extract was then collected. Cells were seeded at a density of 1 x 10⁶ cells / ml in a 96-well plate. 4Cells per well were cultured for 24 hours. After washing the cells with PBS, 100 μL of thermosensitive hydrogel extraction buffer and BiInSn extraction buffer were added. Six replicates were made for each group. After further culturing for 4 hours, the old culture medium was discarded and the cells were rinsed with PBS. 10 μL of CCK-8 reagent and 100 μL of fresh culture medium were added to each well. Then, 100 μL of culture medium was added to each well. Finally, cell viability was tested using a microplate reader.

[0046] BiInSn sheets are made Thin slices were placed in 12-well plates and sterilized with ultraviolet light for 24 hours. Then, 1*10 cells were inoculated onto the alloy slices. 5 Cells per well were cultured in a CO2 incubator at 35°C for 3-7 days, followed by live / dead staining fluorescence assay. The positive control group consisted of GaIn alloy (Ga 24.5 wt%, In 75.5 wt%), and the negative control group consisted of pure culture medium. Results showed that the cell viability of MC3T3-E1 cells cultured in both BiInSn extract and thermosensitive hydrogel extract was higher than 100%. Figure 3 (a) and (b) indicate that both BiInSn and the thermosensitive hydrogel have good biocompatibility. Furthermore, to further test the in vitro biocompatibility of BiInSn, MC3T3-E1 cells were seeded onto sterile culture dishes, BiInSn alloy sheets, and GaIn alloy sheets, respectively. After culturing for 3-7 days, cell viability / deadness staining results showed that BiInSn did not exhibit the significant cytotoxicity seen with GaIn alloy. Figure 3 (c)). Therefore, the above in vitro biocompatibility tests show that neither BiInSn nor the thermosensitive hydrogel exhibits significant biotoxicity.

[0047] Comparative Example 1

[0048] Preparation of low-melting-point alloy: Bismuth (Bi), indium (In), and tin (Sn) were mixed in an empty beaker at mass fractions of 32.5%, 51%, and 16.5%, respectively. The beaker was placed in a vacuum drying oven and heated at 150°C for 3 hours. After melting, the mixture was stirred thoroughly in a magnetic water bath for 4 hours to obtain a low-melting-point alloy material with a melting point of 60°C.

[0049] Preparation of thermosensitive hydrogel: Poloxamer (F127), hydroxypropyl methylcellulose (HPMC), and deionized water were weighed at 10%, 2.5%, and 87.5% by mass and placed in beakers. The beakers were placed in an insulated container filled with ice. The mixture was stirred with a glass rod until it became liquid and had good fluidity. Then, it was placed in a refrigerator at 4°C to allow the thermosensitive hydrogel to fully swell, thus obtaining the thermosensitive hydrogel. The obtained thermosensitive hydrogel was placed in 3ml test tubes and placed in water baths at room temperature (21°C) and 37°C, respectively. The tubes were inverted at 2 min, 8 min, 15 min, 25 min, and 35 min to observe whether it had transformed into a gel. The results showed that the thermosensitive hydrogel prepared in this ratio could not transform into a gel state at 37°C, therefore it could not exist stably in vivo and did not meet the application requirements.

[0050] Comparative Example 2

[0051] First, a low-melting-point alloy is prepared: Bismuth (Bi), indium (In), and tin (Sn) are mixed in an empty beaker at mass fractions of 32.5%, 51%, and 16.5%, respectively. The beaker is placed in a vacuum drying oven and heated at 150°C for 3 hours. After melting, the mixture is stirred thoroughly in a magnetic water bath for 4 hours to obtain a low-melting-point alloy material with a melting point of 60°C.

[0052] Preparation of thermosensitive hydrogel: Poloxamer (F127), hydroxypropyl methylcellulose (HPMC), and deionized water were weighed at 15%, 2.5%, and 82.5% by mass and placed in beakers. The beakers were placed in an insulated container filled with ice and stirred with a glass rod until the mixture became liquid and had good fluidity. Then, the beakers were placed in a refrigerator at 4°C to allow the thermosensitive hydrogel to fully swell, thus obtaining the thermosensitive hydrogel. The obtained thermosensitive hydrogel was placed in 3ml test tubes and placed in water baths at room temperature (21°C) and 37°C, respectively. The tubes were inverted at 2 min, 8 min, 15 min, 25 min, and 35 min to observe whether it had transformed into a gel. The results showed that the thermosensitive hydrogel prepared in this ratio could not transform into a gel state at 37°C, therefore it could not exist stably in vivo and did not meet the application requirements.

[0053] Comparative Example 3

[0054] Preparation of low-melting-point alloy: Bismuth (Bi), indium (In), and tin (Sn) were mixed in an empty beaker at mass fractions of 32.5%, 51%, and 16.5%, respectively. The beaker was placed in a vacuum drying oven and heated at 150°C for 3 hours. After melting, the mixture was stirred thoroughly in a magnetic water bath for 4 hours to obtain a low-melting-point alloy material with a melting point of 60°C.

[0055] Preparation of thermosensitive hydrogel: Poloxamer (F127), hydroxypropyl methylcellulose (HPMC), and deionized water were weighed at 25%, 2.5%, and 72.5% by mass and placed in beakers. The beakers were placed in an insulated container filled with ice and stirred with a glass rod until the mixture became liquid and had good fluidity. Then, the mixture was placed in a refrigerator at 4°C to allow the thermosensitive hydrogel to fully swell, thus obtaining the thermosensitive hydrogel. A portion of the thermosensitive hydrogel was pipetted into a 3ml test tube and placed in a water bath at room temperature (21°C) and 37°C, respectively. The tubes were then inverted and observed at 2 min, 8 min, 15 min, 25 min, and 35 min to see if the hydrogel had transformed into a gel. The results showed that the thermosensitive hydrogel prepared in this ratio transformed into a gel state after 35 min at room temperature (21°C). A glass transition temperature that is too low would cause difficulties in the in vitro preparation stage and would not meet the application requirements.

[0056] Comparative Example 4

[0057] Preparation of low-melting-point alloy: Bismuth (Bi), indium (In), and tin (Sn) were mixed in an empty beaker at mass fractions of 32.5%, 51%, and 16.5%, respectively. The beaker was placed in a vacuum drying oven and heated at 150°C for 3 hours. After melting, the mixture was stirred thoroughly in a magnetic water bath for 4 hours to obtain a low-melting-point alloy material with a melting point of 60°C.

[0058] Using the same method as in Example 2, a hole with a diameter of 8 cm and a depth of 10 cm was drilled in the pig femur to simulate a bone defect. The femur was then placed in a 37°C water bath, and the low-melting-point alloy prepared above was injected into the hole using a conventional syringe. Temperature changes in the bone tissue surrounding the hole were recorded. Figure 4 The results showed that the highest temperature of the surrounding bone tissue could reach 48.62℃. Since the threshold temperature for irreversible osteocyte damage (i.e., bone death or osteonecrosis) reported by existing technology is 47℃, the excessive temperature has already caused some damage to the surrounding bone tissue. (Reference: [1] GC van Rhoon, T.S. Maras, PS. Yarmolenko, MW. Dewhirst, E. Neufeld, N. Kuster. CEM 43℃ thermal dose thresholds: a potential guide for magnetic resonance radiofrequency exposure levels. Eur Radiol, 23 (2013), pp. 2215-2227, 10.1007 / s00330-013-2825-y

[0059] [2]WW Monafo,SG.Eliasson.Sciatic nerve function following hindlimbthermal injuryJ Surg Res,43(1987),pp.344-350,10.1016 / 0022-4804(87)90091-6

[0060] [3] D Xu, M. Pollock. Experimental nerve thermal injury Brain, 117 (1994), pp. 375-384, 10.1093 / brain / 117.2.375)

[0061] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A low-melting-point alloy / thermosensitive hydrogel composite bone cement, characterized in that, The temperature-sensitive hydrogel is wrapped around the outside of the low-melting-point alloy, and the mass-volume ratio of the low-melting-point alloy to the temperature-sensitive hydrogel is 1-3g:1ml. The thermosensitive hydrogel comprises 20 wt% poloxamer, 2.5 wt% hydroxypropyl methylcellulose, and 77.5 wt% deionized water.

2. The composite bone cement according to claim 1, characterized in that, The low-melting-point alloy has a melting point of 45-100℃ and is selected from one or more of gallium-indium alloy, gallium-indium-tin alloy, gallium-indium-tin-zinc alloy, gallium-tin alloy, indium-tin alloy, bismuth-indium alloy, bismuth-tin alloy, bismuth-indium alloy, and bismuth-indium-tin-zinc alloy.

3. The composite bone cement according to claim 2, characterized in that, When the low-melting-point alloy is a bismuth-indium-tin alloy, its raw material formulation is 32.5 wt% metallic bismuth, 51 wt% metallic indium and 16.5 wt% metallic tin.

4. The composite bone cement according to claim 2, characterized in that, Its raw material formula consists of 54wt% metallic bismuth, 29.7wt% metallic indium and 16.3wt% metallic tin.

5. The composite bone cement according to claim 2, characterized in that, Its raw material formula consists of 31.6 wt% bismuth, 48.8 wt% indium and 19.6 wt% tin.

6. The composite bone cement according to claim 2, characterized in that, Its raw material formula is 43.2 wt% bismuth metal, 39.3 wt% indium metal and 17.5 wt% tin metal.

7. The composite bone cement according to claim 2, characterized in that, When the low-melting-point alloy is bismuth-indium-tin-zinc, its raw material formulation is 35wt% metallic bismuth, 48.6wt% metallic indium, 16wt% metallic tin and 0.4wt% zinc.

8. The composite bone cement according to claim 1, characterized in that, The glass transition temperature of the thermosensitive hydrogel is 35-37℃.

9. A method for preparing composite bone cement as described in any one of claims 1-8, characterized in that, Includes the following steps: 1) Preparation of thermosensitive hydrogel: Weigh poloxamer, hydroxypropyl methylcellulose and deionized water in proportion and place them in a beaker. Place the beaker in an insulated container filled with ice and stir until completely mixed. Then place the mixture in a refrigerator at 0~4℃ for 24-36 hours to obtain a thermosensitive hydrogel. 2) Preparation of low-melting-point alloys: Place a beaker containing metal materials of a predetermined ratio in a vacuum drying oven and heat it. Set the heating temperature to 140-160℃ and the duration to 2-4 hours. Then stir the molten metal mixture for 3-5 hours to obtain a uniform low-melting-point alloy material. 3) Preparation of composite bone cement: The low-melting-point alloy material is drawn into the first syringe sleeve using an injection device, keeping the low-melting-point alloy in a liquid state. Then, the temperature-sensitive hydrogel is drawn into the second syringe sleeve using the injection device. The valve of the injection device is then controlled to inject the temperature-sensitive hydrogel into the target area first, and then the molten low-melting-point alloy material is rapidly injected into the temperature-sensitive hydrogel in the target area. After pressure treatment, it is solidified and molded into a support with a controllable structure.

10. The preparation method according to claim 9, characterized in that, The injection device has a Y-shaped structure, which includes three branches, two of which are the first syringe sleeve and the second injection sleeve, and the third branch is the injection outlet; The injection device also includes a three-way valve, which is used to control the connection between the first syringe sleeve or the second injection sleeve and the injection outlet. The first syringe sleeve and the second injection sleeve are each provided with a syringe plunger.

11. The preparation method according to claim 10, characterized in that, The first syringe sleeve and the second injection sleeve are provided with an insulation layer on the outside, and the first syringe sleeve is also provided with a local heating device on the outside.

12. The preparation method according to claim 9, characterized in that, The support can be a solid structure, a hollow structure, or a microporous structure.

13. The preparation method according to claim 9, characterized in that, The pressurization process is performed during injection, and the pressurization method is either gas pressurization or mechanical pressurization.

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