KR20170096268A

KR20170096268A - Acrylic bone cement composite comprising calcium phosphate microsphere uniformly spreaded therein and a preparation method thereof

Info

Publication number: KR20170096268A
Application number: KR1020160017284A
Authority: KR
Inventors: 김현이; 이성미; 강인구
Original assignee: 서울대학교산학협력단
Priority date: 2016-02-15
Filing date: 2016-02-15
Publication date: 2017-08-24
Also published as: KR101815367B1

Abstract

The present invention relates to an acrylic bone cement composite consisting of: a matrix containing an acrylic polymer; and a calcium phosphate-based microsphere uniformly dispersed in the matrix and having average diameter of 10-500 m. The present invention relates to a kit for producing the acrylic bone cement composite, and a production method thereof.

Description

TECHNICAL FIELD The present invention relates to an acrylic-based bone cement composite containing uniformly dispersed calcium phosphate-based microspheres and a method for producing the same.

The present invention relates to a matrix comprising an acrylic polymer; And calcium phosphate-based microspheres having an average diameter of 10 to 500 탆 uniformly dispersed in the matrix, a kit for manufacturing the acrylic-based bone cement composite, and a method for producing the same.

Recent advances in medical technology have resulted in the use of artificial organs or implantable materials to replace and repair damaged areas within the body, which are called implants. Implants are implants that are used to support or adhere tissues during treatment, such as molded parts that can be implanted in an organ organs, such as membranes, fixed laminates, tractional or spatial components, screws, pins, rivets, Is used for the purpose of separating the tissue from other tissues.

Implants are gradually being widened, and thus much research is underway on the development of implants. Typical materials for implants used for medical treatment include metals, ceramics, and polymers. However, implant materials used in the human body must have biocompatibility, blood compatibility when contacting blood, and direct contact with biological tissues or cells other than blood. tissue compatibility is required, the available implant materials are very limited.

Specifically, metallic implants are excellent in mechanical properties and processability, but have disadvantages such as stress shielding, image degradation and implant migration. In the case of ceramic implants, biocompatibility is relatively high But it is disadvantageous in that it is likely to be damaged by an external impact and is difficult to be processed. In addition, the polymer implant has a relatively weak strength.

Therefore, polymer materials which are harmless to the human body and have excellent moldability and stable physical properties are in the spotlight. Particularly, since biodegradable polymers are decomposed after a lapse of a predetermined time, they are biodegradable Foreign matter reaction can be minimized.

However, the biodegradable polymer has relatively poor physical properties as compared with other polymers, and biodegradable polymers such as lactic acid, glycolic acid, caproic acid, maleic acid, phosphazene, hydroxybutyric acid, hydroxyethoxyacetic acid, sebacic acid, Acidic substances such as glycols, amino acids, formalin, alkylcyanoacrylates and the like are produced and cause inflammation reaction and cytotoxicity in the human body.

On the other hand, acrylic polymer such as polymethyl methacrylate (PMMA) is widely known as bone cement. It enhances the bonding force between the implant and the bone inserted in the body, It is used to support the load by filling the damaged part by the back. However, the adhesion to the bone is somewhat low, and the bone is not well connected with the inside of the body. Therefore, in order to improve this, a method of coating bioactive metal on the surface or compounding it with ceramics has been carried out. As a part of this effort, various biologically active materials such as chitosan and silica are being studied, but it takes a long time for these materials to be replaced with bone tissue due to a slow biodegradation rate.

In addition, since it has a property of transmitting X-rays due to the property of polymer, it is difficult to monitor the implanted position and / or condition itself when it is used as a graft inserted into a body to replace a damaged bone tissue. However, these contrast agents are not only poor in biological characteristics but also have a disadvantage in that they cause toxicity in the body in the case of barium, for example.

The present inventors have made intensive researches to find a conjugate capable of imaging through X-rays while improving biocompatibility in bone cements based on acrylic polymers. As a result, they have found that a calcium phosphate compound is dispersed evenly in an acrylic polymer matrix in the form of microspheres The present inventors confirmed that the prepared complexes exhibit excellent biocompatibility and can be detected by X-rays themselves without a separate contrast agent, thus completing the present invention.

A first aspect of the present invention relates to a matrix comprising an acrylic polymer; And calcium phosphate microspheres having an average diameter of 10 to 500 占 퐉 uniformly dispersed in the matrix.

A second aspect of the present invention is a powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate-based microsphere; And a liquid composition comprising a non-crosslinked acrylic polymer monomer and a free radical active agent.

A third aspect of the present invention is a method for preparing a powder composition comprising a first step of preparing a powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate-based microsphere; A second step of preparing a liquid composition comprising a non-crosslinked acrylic polymer monomer, and a free radical activator; A third step of mixing and kneading the powder component and the liquid component; And a fourth step of injecting the calcium phosphate-based microspheres into a mold of a desired shape to form an acrylic-based bone cement composite comprising calcium phosphate-based microspheres.

Hereinafter, the present invention will be described in detail.

The present invention relates to an acrylic-based bone cement composite which is prepared by dispersing calcium phosphate-based microspheres evenly on a matrix containing an acryl-based polymer to improve biocompatibility and / or bone regeneration ability and, It can be used as a monitorable implant by itself. For example, when the calcium phosphate compound is added in the form of a powder unlike the complex of the present invention, the components may not be uniformly dispersed in the matrix due to aggregation of the particles, and the particles may be unevenly dispersed to deteriorate the mechanical properties of the composite .

As described above, the calcium phosphate-based microspheres preferably have a diameter of 10 to 500 mu m. When prepared to the above-mentioned size, the contrast can be secured, and the void space can be easily restored by osteocytes and / or other living tissues when biodegraded in the body to form pores. For example, the biodegradable calcium phosphate microspheres may be finally decomposed to secure a space useful for the bone tissue to come in.

The calcium phosphate microspheres may be prepared by water-in-oil emulsion or by spray drying.

The term "composite" used in the present invention means a material having excellent properties physically and chemically different from the original material by combining two or more kinds of materials, And a structure in which calcium-based microspheres are embedded.

The acrylic-based bone cement composite of the present invention may contain calcium phosphate microspheres in an amount of 1 to 50% by volume. Preferably 20 to 40% by volume, but is not limited thereto. If the content of the calcium phosphate microspheres is less than 1 vol%, it may be difficult to attain the desired degree of biocompatibility and / or enhancement. If the content exceeds 50 vol%, the acrylic bone cement matrix itself Can be reduced and the compressive strength can be reduced to an acceptable level or higher.

The calcium phosphate-based microspheres may include, but are not limited to, one or more calcium phosphate compounds selected from the group consisting of tricalcium alpha-phosphate, tricalcium beta-phosphate, hydroxyapatite, and calcium phosphate . For example, as the calcium phosphate microspheres, materials having biocompatibility, biodegradability, and contrasting properties detectable by X-rays can be used without limitation.

For example, the acrylic-based bone cement composite can be used for an aggregate replanting graft.

The term "implant " as used in the present invention includes artificial organs or implantable materials used for replacing and repairing a damaged part in the human body, Used to support or adhere tissue during treatment, such as a molded part, such as a membrane, a fixed thin plate, a three dimensional or spatial component, or a fixation means such as screws, pins, rivets, . The implant of the present invention may be used for bone replacement. The transplant of the present invention has improved biocompatibility and is advantageous for cell adhesion. In addition, calcium phosphate microspheres embedded in the complex after being transplanted into a living body decompose with time to form pores, and new bone cells It can be filled, and it can exhibit an excellent bone regeneration effect beyond a simple bone substitution effect.

According to one embodiment of the present invention, when the osteoclast cell line (MC3T3-E1 cells) was cultured together with the acryl-type PMMA bone cement complex containing the calcium phosphate microspheres of the present invention, On the surface of the PMMA bone cement not containing the calcium phosphate microspheres used as the control group, an initial adhesion state in which some rounded cells were attached was observed, while the alpha-phosphate tricalcium microspheres of the present invention were observed at 20 and 40 The volume of the bone cement composite contained a large amount of cells throughout the complex as well as a considerable number of cells compared with the control group (FIG. 6). This means that the bone cement complex containing the calcium phosphate microspheres of the present invention has a good affinity with the cells. Therefore, the bone cement composite containing the calcium phosphate microspheres of the present invention can be usefully used as an implant for living body implantation.

In addition, complexes containing alpha-calcium triphosphate in the same amount but in the form of powder rather than microspheres still exhibited transmittance to X-rays, but in the case of the complex of the present invention containing this in the form of microspheres, (FIG. 5), which can be detected by X-ray without adding a contrast agent, can be usefully utilized as a living implant for implantation which does not require a contrast agent.

The present invention also relates to a powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate microsphere; And a liquid composition comprising a non-crosslinked acrylic polymer monomer, and a free radical active agent, can be provided.

In the kit of the present invention, the acrylic polymer may be a polymer of the non-crosslinked acrylic polymer monomer, and may be provided in powder or bead form. For example, when an acryl-based polymer in the form of beads is used, the size may be 10 to 50 mu m in diameter But is not limited thereto.

For example, the acrylic polymer may be polymethyl methacrylate, polymethyl acrylate, polystyrene, or a copolymer thereof, but is not limited thereto, and acrylic-based bone cement known in the art can be used.

For example, the free radical initiator may be benzoyl peroxide. The free radical initiator may be included in an amount of 0.3 to 1% by weight based on the total weight of the powder composition.

On the other hand, the free radical activator may be N, N-dimethyl-para-toluidine. The free radical activator may be included in an amount of 0.7 to 1.3% by volume based on the total volume of the liquid composition.

The content of the free radical initiator and the activator in the composition is a factor that controls the viscosity of the dough formed when the bone cement composite is prepared by mixing the powder composition and the liquid composition. If the viscosity is too high, It may be low or high and may be disadvantageous for molding. For example, it may be difficult to produce a desired shape or to realize a microstructure by curing in a too short time, and it may take too much time for curing to cause unnecessary delay of the processing time.

The kit for preparing an acrylic-based bone cement composite of the present invention comprises a powder composition and a liquid composition separately and has a dough time viscosity immediately when the composition is mixed at a predetermined ratio. The liquid- Cement composite.

The preferred mixing ratio of the powder composition and the liquid composition is preferably 1.5 to 2 g of the powder composition per 1 mL of the liquid component.

The acrylic bone cement composite containing calcium phosphate microspheres of the present invention comprises a first step of preparing a powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate microsphere; A second step of preparing a liquid composition comprising a non-crosslinked acrylic polymer monomer, and a free radical activator; A third step of mixing and kneading the powder component and the liquid component; And a fourth step of molding by injection into a mold of the desired type.

For example, the dough in the third step may be continued until the dough is not touched by hand.

In the fourth step, curing by polymerization of the acrylic polymer monomer may occur during molding.

For example, in order to remove the remaining monomer after the curing of the fourth step, a fifth step of holding at 15 to 50 캜 for 3 to 24 hours may be further performed.

For example, since the MMA monomer can easily diffuse in water or even in air, it can be volatilized and removed only by applying a little heat and leaving it for several hours.

Since it contains calcium phosphate microspheres of a predetermined size uniformly dispersed in the acrylic polymer matrix of the present invention, it exhibits excellent biocompatibility and is itself a composite that can be visualized through X-rays. Therefore, Since it can be detected by X-ray, it is possible to provide a monitor which is easy to monitor. The calcium phosphate microspheres embedded in the complex are decomposed as time passes after being implanted in the living body, Since the cells can be filled, an excellent bone regeneration effect can be expected.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 schematically shows an example of a method for producing tricalcium α-phosphate microspheres according to the present invention. FIG.
Figure 2 is a diagram showing the surface of (a) tricalcium phosphate alpha-microspheres and (b) hydroxyapatite microspheres prepared according to one embodiment of the present invention, as observed with a scanning electron microscope.
FIG. 3 is a graph showing an X-ray diffraction spectrum of (a) tricalcium α-phosphate microsphere and (b) hydroxyapatite microsphere prepared according to an embodiment of the present invention, in comparison with each powder.
4 is a graph showing (a) compressive strength and (b) stiffness of a composite containing 20 and 40% by volume of tricalcium phosphate microspheres prepared according to an embodiment of the present invention. As a control, pure PMMA containing no calcium phosphate microspheres was used.
FIG. 5 is a diagram showing micro CT measurement results of a composite containing 20% and 40% by volume of tricalcium α-phosphate microspheres prepared according to an embodiment of the present invention. As the control group, a complex containing calcium phosphate-based compounds having the same components and contents in powder form was used.
Figure 6 shows the shape of cells cultured on a composite surface containing (a) pure PMMA surface or (b) and (c) 20% and 40% by volume tricalcium phosphate microspheres according to the invention, respectively Which is observed with a scanning electron microscope.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited by these examples.

Example 1: Alpha- Tricalcium phosphate Microsphere Acrylic containing Of bone cement Produce

1-1. Alpha- Tricalcium phosphate Preparation of powder

Calcium hydrogen phosphate (CaHPO ₄ ) and calcium carbonate (CaCO ₃ ) were mixed at a molar ratio of 3.5: 1 and ball milled using ethanol as a solvent. The obtained powder was dried at 40 to 50 占 폚 for 1 day and then put into a platinum crucible and heat-treated at 1300 占 폚 for 6 hours and quenched. After sufficiently cooling, the mixture was pulverized in a mortar bowl in a vacuum state and sieved to a size of 20 μm or less to obtain tricalcium alpha-phosphate powder.

1-2. Alpha- Tricalcium phosphate Microsphere Produce

An example of a process for producing tricalcium phosphate microspheres according to the present invention is schematically shown in FIG. Specifically, an emulsion solution containing 10 mL of olive oil and 0.5 mL of Labrafil as a surfactant was prepared by stirring at 10 ° C at 500 revolutions per minute. 1 g of the alpha-calcium phosphate tricalcium phosphate powder prepared according to Example 1-1 was mixed with citric acid (0.6 mL) diluted to 20 mass% in distilled water, and the resulting paste was dispersed in the prepared emulsion solution, The microspheres were prepared by emulsification. The resulting microspheres were sieved to obtain microspheres having an average diameter of 100 to 500 μm.

1-3. Alpha- Tricalcium phosphate Microsphere Acrylic containing Bone cement Manufacture of Composites

As a free radical initiator, the total mass of the powder components other than the trace amount of benzoyl peroxide was 2 g, and 2 g of polymethyl methacrylate (PMMA) powder as an acrylic polymer, And then mixed with 0.01 g of benzoyl peroxide so as to have 20 to 40% by volume (that is, 50 to 70% by mass) of the prepared alpha-calcium tricalcium microspheres. Separately, 1 mL of methyl methacrylate (MMA) monomer as a non-crosslinked acrylic polymer monomer was mixed with 10 μL of N, N-dimethyl-para-toluidine used as a free radical activator to prepare a liquid component. The powder components and the liquid components prepared at the above-mentioned room temperature were mixed, and they were stirred by hand until the dough was not touched. As described above, when the dough is touched, the dough is put into a syringe and molded into a 6 mm or 12 mm diameter mold. After sufficient curing, the remaining monomer was removed by storing in an oven at 37 ° C for one day.

Example 2: hydroxyapatite Microsphere Acrylic containing Of bone cement Produce

2-1. Hydroxyapatite Microsphere Produce

Hydroxyapatite microspheres were prepared by spray drying. Specifically, 0.1% by weight of oligomer polyester (Hypermer KD-6) as a 1.5% by weight dispersant of polyvinyl butyral (PVB) as a binder and 4 g (40% by weight) of hydroxyapatite powder were added to 10 mL of ethanol The microspheres were prepared by spraying with a nozzle having a size of 1 mm under conditions of a temperature of 30 ° C and a wind speed of 0.15 MPa or higher in the sprayer. Thereafter, the binder and dispersant were removed by heat treatment at 500 ° C for 10 hours, and sintered at 1350 ° C for 2 hours to finally obtain hydroxyapatite microspheres.

2-2. Hydroxyapatite Microsphere Acrylic containing Bone cement Manufacture of Composites

20 to 40% by volume (i.e., 50 to 80 mass%) of the hydroxyapatite microspheres prepared according to Example 2-1 in place of 20 to 40% by volume (i.e., 50 to 70 mass%) of the tricalcium- %) Was used in place of the hydroxyapatite microspheres to prepare an acrylic-based bone cement composite containing hydroxyapatite microspheres in the same manner as in Example 1-3.

Experimental Example 1: Scanning electron microscope analysis

The surface morphology of the calcium phosphate microspheres obtained from Examples 1-2 and 2-1 was coated with platinum and observed with a scanning electron microscope (SEM). The results are shown in FIG. 2 Respectively. As shown in Fig. 2, alpha-calcium phosphate (Fig. 2a) and hydroxyapatite (Fig. 2b) were formed into spherical particles having diameters of 250 to 500 [mu] m and 100 to 250 [mu] m, respectively.

Experimental Example 2: XRD analysis

Spectrum of tricalcium phosphate microspheres (red solid line) obtained from Example 1-2 using the X-ray diffractometer was compared and compared with the spectra of the powder of the same component (black solid line) The results are shown in Fig.

As shown in FIG. 3A, peaks of alpha-calcium tricalcium phosphate crystals were observed from both the microspheres represented by the red solid line and the solid black line, and the X-ray diffraction spectrum of the calcium triphosphate in the form of powder, Indicating that the alpha-calcium phosphate crystal form remains after the preparation. Furthermore, it is shown that complexes containing alpha-calcium trichromate microspheres can maintain excellent biocompatibility of alpha-calcium phosphate.

The X-ray diffraction spectrum of the hydroxyapatite microsphere obtained in Example 2-1 was obtained and shown in FIG. 2B. As shown in FIG. 2B, a peak of the hydroxyapatite crystal was observed from the X-ray diffraction spectrum of the hydroxyapatite microsphere, indicating that the hydroxyapatite crystal form was retained even after the microspheres were prepared. Furthermore, it is shown that the complex containing hydroxyapatite microspheres can maintain excellent biocompatibility of hydroxyapatite.

Experimental Example 3: Analysis of mechanical properties

The mechanical properties of the PMMA bone cement composite containing alpha-tricalcium phosphate microspheres prepared according to Example 1 of the present invention were analyzed. First, five specimens of 6 mm in diameter and 12 mm in height were prepared in accordance with ISO 5833 for compressive strength measurement. The samples were prepared from pure PMMA and complexes containing 20% by volume and 40% by volume of tricalcium phosphate microspheres, respectively. Each specimen was measured with a compressive strength measuring machine at a speed of 1 mm per minute and the compressive strength was calculated by dividing the 2% offset load derived therefrom by the cross-sectional area of the specimen. The stiffness of the specimen was obtained by calculating the slope of the graph. Compressive strength and stiffness of the specimens thus measured are shown in FIGS. 4A and 4B, respectively.

As shown in FIG. 4A, the compressive strength of pure PMMA is about 100 MPa. In contrast, in the case of the PMMA bone cement composite containing alpha-tricalcium phosphate microspheres, the content of tricalcium phosphate microspheres But the reduction is within a tolerance range. This indicates that the PMMA bone cement composite containing alpha-tricalcium phosphate microspheres according to the present invention has a compressive strength similar to that of pure PMMA .

On the other hand, as shown in FIG. 4B, the stiffness of the composite increased as the content of tricalcium phosphate microspheres increased. However, since all of the three specimens did not show a large difference compared to the stiffness of human bones, it can be expected that when placed in the human body, no side effects due to the stress shielding phenomenon will appear.

The complexes containing the hydroxyapatite microspheres prepared according to Example 2 were also tested in the same manner and the results showed similar trends to those for the complexes comprising the alpha-tricalcium phosphate microspheres.

Experimental Example 4: Cho Young-sung analysis

In order to confirm the contrast of the PMMA bone cement composite containing the alpha-tricalcium phosphate microspheres prepared according to Example 1, microcontrast analysis was performed and the results are shown in FIG. Specifically prepared as a composite according to Example 1-3 under the same conditions with 20 and 40% by volume of the microspheres in the form of powder and the microsphere form of alpha-phosphate prepared according to Example 1-2, respectively, CT images were taken. As a result, regardless of the content, in the case of the composite containing the alpha-calcium phosphate powder, the microcontent of the alpha-calcium phosphate component contained in the PMMA bone cement as well as the microcontainer could hardly be discerned, In the case of the composite containing microspheres, the outline of the PMMA bone cement composite is difficult to identify, but the alpha-calcium phosphate grains contained therein are clearly identified, and the hydroxyapatite microspheres prepared according to Example 2 The complexes also exhibited the same characteristics. From this, it can be confirmed that the composite prepared by the method according to the embodiment of the present invention has a uniform distribution of calcium phosphate-based microspheres, for example, alpha-calcium phosphate or hydroxyapatite microspheres.

Experimental Example 5: Osteoclast culture

In order to confirm the biocompatibility of the acrylic-based bone cement composite containing the calcium phosphate-based microspheres prepared according to the embodiment of the present invention, an acrylic-based bone cement composite containing calcium phosphate microspheres containing the microspheres, The mouse-derived MC3T3-E1 cells as pre-osteoblasts were cultured to observe whether the cells adhered to the surface of the complex and / or the shape of the cells adhered to the surface of the complex, and the results are shown in FIG. 6 Respectively.

Before the cells were dispensed, the complex prepared in the form of disks 12 mm in diameter and 2 mm in height was washed in 70 vol% ethanol for 1 hour, sterilized in an autoclave at 121 ° C for 15 minutes, and then treated with ultraviolet rays for one day. As a control group, pure PMMA disks of the same size were sterilized by the same method. The sterilized disk-shaped specimen (PMMA complex containing pure PMMA, 20% by volume and 40% by volume microspheres) was placed in each well of a 4-well plate and 1 mL of cell suspension X 10 < ⁴ > cells / mL) was dispensed into each well. The cells on the specimen were incubated in a 95% CO ₂ incubator for 1 day, and then the shape of the cells attached to the surface of the complex was observed.

To this end, the cells with attached cells were fixed with glutaraldehyde, dehydrated with a series of gradient ethanol (50%, 70%, 90%, 95% and 100%) and then dissolved in hexamethyldisilazane Treated with platinum and observed with a scanning electron microscope. The results are shown in Fig.

As shown in Fig. 6A, it was confirmed that cells cultured on a pure PMMA specimen did not extend the stomach and maintained a relatively circular shape. On the other hand, as shown in FIG. 6B, it was confirmed that the cells cultured on the complex sample containing alpha-calcium trichospores microspheres were well adhered to the surface of the microsphere (red dotted line) and extended along the surface. In addition, as shown in FIG. 6C, when the content of tricalcium α-phosphate microsphere was increased, the cell gain was well adhered to the surface of the microsphere, and it was confirmed that the neighboring cells crossed with each other. This indicates that the cells were selectively attached to the surface of tricalcium phosphate microspheres and that the biocompatibility of the complexes was improved by containing the alpha-tricalcium phosphate microspheres.

Experiments were carried out in the same manner on the composite containing hydroxyapatite prepared in Example 2, and the results were similar to those described above.

Claims

A matrix containing an acrylic polymer; And calcium phosphate microspheres having an average diameter of 10 to 500 占 퐉 uniformly dispersed in the matrix.

The method according to claim 1,
Wherein the content of the microspheres is 1 to 50% by volume.

The method according to claim 1,
Wherein the calcium phosphate-based microspheres comprise at least one calcium phosphate compound selected from the group consisting of tricalcium alpha-phosphate, tricalcium beta-phosphate, hydroxyapatite, and calcium phosphate.

The method according to claim 1,
Wherein the calcium phosphate-based microspheres are biocompatible, biodegradable and capable of being detected by X-ray.

The method according to claim 1,
Wherein the acrylic-based bone cement composite is used in an aggregate implantable implant.

A powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate-based microsphere; And
1. A kit for preparing an acrylic-based bone cement composite comprising a liquid composition comprising a non-crosslinked acrylic polymer monomer and a free radical active agent.

The method according to claim 6,
Wherein the acrylic polymer is a polymer of the non-crosslinked acrylic polymer monomer and is in powder or bead form.

The method according to claim 6,
Wherein the acrylic polymer is polymethyl methacrylate, polymethyl acrylate, polystyrene, or a copolymer thereof.

The method according to claim 6,
Wherein the free radical initiator is benzoyl peroxide.

The method according to claim 6,
Wherein the free radical initiator is contained in an amount of 0.3 to 1% by weight based on the total weight of the powder composition.

The method according to claim 6,
Wherein the free radical active agent is N, N-dimethyl-para-toluidine.

The method according to claim 6,
Wherein the free radical active agent is included in an amount of 0.7 to 1.3% by volume based on the total volume of the liquid composition.

The method according to claim 6,
Wherein the powder composition and the liquid composition are mixed in a ratio of 1.5 to 2 g of the powder composition to 1 mL of the liquid composition and used.

A first step of preparing a powder composition comprising an acrylic polymer, a free radical initiator, and a calcium phosphate-based microsphere;
A second step of preparing a liquid composition comprising a non-crosslinked acrylic polymer monomer, and a free radical activator;
A third step of mixing and kneading the powder component and the liquid component; And
And a fourth step of injecting the calcium phosphate-based microspheres into a mold of a desired shape to form an acrylic-based bone cement composite.

15. The method of claim 14,
And curing by polymerization of the acrylic polymer monomer occurs during molding in the fourth step.

16. The method of claim 15,
And a fifth step of holding the solution at 15 to 50 DEG C for 3 to 24 hours after the fourth step.

An implant prepared from the acrylic-based bone cement composite of any one of claims 1 to 5.

18. The method of claim 17,
Wherein the graft is an implant for bone regeneration which can be imaged by X-rays.