KR100331990B1 - Bone substituent consisting of biodegradable porous calcium metaphosphate and its process of preparation - Google Patents

Abstract

The present invention relates to an artificial synthetic bone composed of porous calcium metaphosphate ceramics having excellent biocompatibility and bone affinity, and a method for manufacturing the same, and specifically, a calcium metaphosphate slurry is coated on a hydrophilic surface-treated polyurethane sponge and then sintered. The biodegradable porous calcium phosphate bone graft material of the present invention has superior biocompatibility and bone affinity compared to conventional bone graft material, so that it is well fused without foreign body reaction with tissues of the graft site and the graft site after bone graft. Decomposed in and absorbed into the living body because it is excellent in osteoinduction can be useful as a bone graft material and cell support. In addition, it can be manufactured to have fine pores, so that it can be applied as an implant for small bone defects such as periodontal lesions.

Description

Bone substituent consisting of biodegradable porous calcium metaphosphate and its process of preparation}

The present invention relates to a bone graft material consisting of biodegradable porous calcium metaphosphate (Calcium Metaphosphate) and a method for producing the same.

In general, autologous bone or allogeneic bone graft for the repair of bone defects has been used for a long time and is now widely used. However, autologous bone has a disadvantage in that it cannot obtain a sufficient amount to recover the entire bone defect and requires secondary surgery at the donor site, and in the case of allogeneic bone, there is a possibility that some infectious diseases are transmitted. To this end, a sufficient amount of bone can be easily obtained, and a bone graft material has been developed and used that has no potential for transmission of disease.

Representative materials used as bone graft materials include calcium phosphate-based ceramics such as hydroxyapatite (HA), tricalcium phosphate (TCP), polymers, bioglass, and calcium carbonate (calcium). carbonate) and clinical results using these materials have been reported. However, recent data show that they have only biocompatibility and no histological osteoinduction, and that most of them are separated from bone tissue by interposition of connective tissue after the procedure. In order to prevent the bone graft material from being separated from the bone tissue, it has been found that the bone graft material is more advantageous to bone regeneration. There is a need for a biodegradable bone graft material that is not only excellent in biocompatibility but also can be appropriately absorbed during transplantation and replaced with regenerated bone.

On the other hand, recently, tissue regeneration procedures have been proposed to artificially form tissues by separating and culturing cells from tissues to be regenerated, inoculating them into appropriate biomaterials, and amplifying and culturing them. In order to inoculate and culture the tissue cells in the tissue regeneration procedure, a cell support is required, and the cell support must also be a biomaterial having excellent tissue compatibility and cell adhesion.

When bone is regenerated using the tissue regeneration procedure, the cell support is currently a collagen matrix, poly (glycolic acid] mesh, PGA mesh), polylactic-CO-glycolic acid foam [poly (lactic-co-glycolic acid) foam, PLGA], calcium phosphate ceramics, polylactide-CO-glycolic acid / polyapatite complex [poly (lactide-co-glycolic acid) / hydroxyapatite, PLGA / HA], and polyphosphazennes (polyphosphazennes) and the like have been studied, but the situation is still scattered for applications to be applied in vivo.

Looking at each of the problems of the cell support, collagen, weak strength, difficult to control the rate of absorption, and because it is usually used to extract from a heterogeneous or homogeneous object, may cause an immune response, in the case of PGA mesh, It is very thin (about 100㎛), which makes it difficult to use when the bone defect is large and its strength is weak.In the case of PLGA copolymer, the hydrophobicity is so large that it is difficult to penetrate and diffuse the medium to the deep part of the cell support. have. In addition, the ceramics used in the past have excellent biocompatibility due to the chemical composition similar to that of natural bone, but the degradation rate is too slow, which may cause obstacles to the bone tissue formed at the transplantation site. More research is still needed.

Since porous ceramics have been recently developed and put into practical use as bacterial filter media, they have been used in various fields such as environment and construction. Recently, it is possible to precisely control the physical and chemical properties of pores, making it possible to use even advanced fields such as semiconductors and biomaterials. It is expanding. In particular, porous calcium phosphate-based ceramics containing hydroxyapatite as a main component have been spotlighted as biomaterials because of their excellent biocompatibility because their chemical composition is similar to that of bone. As such, hydroxyapatite ceramics can replace damaged human organs or some hard tissues and can be used as cell support for culturing bone tissue. However, hydroxyapatite is too slow to decompose and may cause obstacles in newly formed bone tissue. Recently, hydroxyapatite is not only excellent in biosynthesis and bone affinity, but also after a certain period of time after surgery. In accordance with bone regeneration, a lot of research is being conducted on biodegradable materials that can be decomposed and absorbed in the human body and replaced with regenerated bone.

Therefore, the present inventors have found that calcium metaphosphate is biodegradable among calcium phosphate compounds having excellent biosynthesis and bone affinity, as a result of research to develop a bone graft material having excellent biocompatibility and bone affinity and biodegradability. The present invention was completed by preparing the used porous ceramics.

An object of the present invention is to use biodegradable calcium metaphosphate (CMP), excellent biocompatibility and bone affinity, excellent bone induction, can control various decomposition rate and easy to manufacture in various forms bone graft material and bone The present invention provides a biodegradable porous bone graft material suitable for use as a cell support for formation and a method for producing the same.

1 shows a biodegradable porous calcium metaphosphate (abbreviated as 'CMP') block of the present invention,

Figure 2 shows the TG / DTA curve of the Ca (H ₂ PO ₄ ) ₂ powder of the starting material of the present invention,

3 shows the X-ray diffraction diagram of the Ca (H ₂ PO ₄ ) ₂ powder heat-treated at various temperatures,

Figure 4 shows the X-ray diffraction diagram of the CMP with the change of the holding time at the melting temperature of 1050 ℃,

FIG. 5A is a 50-fold magnification of a four-week photograph of a bone graft composed of CMP transplanted into male rabbit subcutaneous connective tissue . FIG .

5B is a 50-fold magnification of a 6-week photograph of a bone graft composed of CMP transplanted into male rabbit subcutaneous connective tissue.

6A is a 50-fold magnification of a 4 week course photograph of a bone graft composed of CMP transplanted into male rabbit muscle tissue.

6b is a 50-fold magnification of a 6-week photograph of a bone graft composed of CMP transplanted into male rabbit muscle tissue,

FIG. 7A is a 2.5-fold magnification of a 4-week course photograph of a bone graft composed of CMP transplanted into a male rabbit skull defect . FIG .

FIG. 7B is a 25-fold magnification of a 4-week course photograph of a bone graft composed of CMP transplanted into a male rabbit skull defect . FIG .

FIG. 8A is a 2.5-fold magnification of a 6-week photograph of a bone graft composed of CMP transplanted into a male skull defect.

FIG. 8B is a 25-fold magnification of a 6-week photograph of a bone graft composed of CMP transplanted into a male skull defect.

Explanation of symbols on the main parts of the drawings

C: Bone graft consisting of transplanted CMP F: Muscle fiber

m: marrow N: new bone

R: New bone infiltrated by CMP degradation T: Connective tissue layer surrounding CMP

Y: bone where deposition occurred by direct contact with CMP W: endpoint of wound

In order to achieve the above object, the present invention provides a biodegradable porous bone graft material, characterized in that composed of calcium metaphosphate (hereinafter abbreviated as 'CMP').

In addition, the present invention comprises the steps of 1) surface-modified polyurethane polymer sponge; 2) mixing the calcium metaphosphate powder with water and preparing a calcium metaphosphate slurry by adding 1-3 wt% of a dispersion stabilizer, 3-7 wt% of a crack inhibitor, and 3-7 wt% of a binder; 3) coating the sponge with calcium metaphosphate and drying by immersing the sponge of step 1 in the calcium metaphosphate slurry of step 2; And 4) sintering and cooling the sponge of step 3 (step 4) to provide a method for producing a bone graft material consisting of calcium metaphosphate (see Figure 1 ).

Hereinafter, the present invention will be described in detail.

Calcium metaphosphate is a calcium phosphate compound, which is chemically very stable and biodegradable that is decomposed and excreted in vivo. Calcium metaphosphate (hereinafter referred to as 'CMP') has a chemical formula of [Ca (PO ₃ ) ₂ ] _n and a molar ratio of calcium (Ca) and phosphorus (P) is about 0.5. CMP is a tetrahedron of PO ₄ ^3- is repeatedly connected to, the two oxygen present in the side edge of the tetrahedron has a structure that is combined with one of calcium. Such CMP exists in crystalline and amorphous forms, and there are four phases in which the tetrahedral structure has different lengths depending on the preparation method and temperature. Such CMP is made of a large number of amorphous fibers have been mainly used as reinforcement for asbestos cloth or composite materials.

The present inventors have confirmed that such CMP has excellent biosynthesis and bone affinity, and even biodegradability, and has developed a method of ceramicizing CMP and using it as a bone graft material. Ceramicization of these CMPs is very stable and not only bone graft material that can replace damaged organs or some hard tissues, but also has excellent characteristics as a cell support for tissue culture of bones. It has the property of disintegrating and disappearing in the human body, and this biodegradation induces the production of bone tissue to help the bone regeneration.

Calcium metaphosphate is present in four phases of α, β, γ, and δ depending on the production method and temperature, all of which can be used as a bone graft material, and among these, β-calcium metaphosphate is chemically stable and is preferable as a bone graft material.

Hereinafter, a method for producing β-calcium metaphosphate will be described.

β-calcium metaphosphate is prepared from biodegradable porous β-phase Ca (PO ₃ ) ₂ (CMP) by heating with mono calcium phosphate Ca (H ₂ PO ₄ ) ₂ (Aldrich) as a starting material.

The Ca (H ₂ PO ₄ ) ₂ powder was put in a platinum crucible and melted in an electric furnace at 3 ° C./min up to 1050 ° C. to maintain a molten state for 8 hours to increase homogeneity of the melt. The product is recrystallized at 900 ° C. for 3 hours and then cooled to 3 ° C./min at a cooling rate to obtain β-CMP ceramics.

Ca (H ₂ PO ₄ ) ₂ Differential thermal analysis

When Ca (H ₂ PO ₄ ) ₂ is heated, an endothermic reaction occurs at two locations (284 ° C. and 986 ° C.) and an exothermic reaction at one location (510 ° C.). The first endothermic reaction occurs at 284 ° C, with a 7.5% (0.87 mg) weight loss. This is because Ca (PO ₃ ) ₂ is formed by volatilization of two water molecules of Ca (H ₂ PO ₄ ) ₂ . And the endothermic reaction at the second 986 ℃ indicates that the Ca (H ₂ PO ₄ ) ₂ powder is melted. An exothermic reaction occurs at 510 ° C., which means that the Ca (H ₂ PO ₄ ) ₂ powder crystallized at 510 ° C. after the first endothermic reaction occurred at 284 ° C. (see FIG. 2).

X-ray Diffraction

As a result of X-ray diffraction analysis of the data obtained by the differential thermal analysis, the starting material is in the state of Ca (H ₂ PO ₄ ) ₂ · H ₂ O by hydration reaction with moisture in the air at room temperature, 200 ℃ In the sample heat-treated with water, the water molecules adsorbed on the surface of Ca (H ₂ PO ₄ ) ₂ · H ₂ O are removed and replaced with anhydrous Ca (H ₂ PO ₄ ) ₂ . Anhydrous β-Ca (PO _{3) 2} as the number of crystal degradation of β-Ca in 510 ℃ (PO ₃₎ at least 284 ℃ form a _second decision. In the heat treatment at 500 ° C. or higher, the crystallinity of β-CMP increases while the water remaining in β-CMP continuously evaporates to the melting point of 986 ° C. (see FIG. 3).

Rapid cooling of the sample heated to 1000 ° C. and 1100 ° C. produces amorphous β-CMP, and slow cooling results in recrystallization into crystalline β-CMP phase (see FIG. 3). Different phases are formed at different holding times at 1050 ° C. In other words, the β-CMP phase shifts to 3 h for 3 hours, and changes to the δ-CMP phase for 10 h (see FIG. 4).

Changes in Pore Shape and Size According to Heat Treatment Temperature

When Ca (H ₂ PO ₄ ) ₂ is heat treated, cylindrical pores are not formed at 909 ° C. or lower, and cylindrical pores are formed at 1000 ° C. or higher. That is, after Ca (H ₂ PO ₄ ) ₂ powder is completely melted at 986 ° C. or higher, recrystallization from Ca (PO ₃ ) ₂ is performed, and cylindrical pores are formed. The formed pores are formed in one direction with respect to the crystal nucleus, and are formed by crossing small pores with each other on the inner surface of the large pores. The pore diameter is formed in various sizes from large pores to very small pores. The diameter of the smallest pores is about 15 μm, and the diameter of the large pores gradually decreases as the holding time at the melting temperature (1050 ° C.) increases. . The longer the holding time at the melting temperature, the more homogeneous the melt, homogenous nucleation and crystal growth of B-Ca (PO ₃ ) ₂ occur, resulting in a smaller pore diameter and an increase in the number of pores.

Hereinafter, a method for producing porous calcium metaphosphate ceramics will be described.

In general, surgical fixtures or bone substitutes need to be removed after implantation, causing pain and economic burden on patients. Therefore, it is required to develop bone graft material that is decomposed and absorbed naturally in the human body after a certain period of time while being implanted in a relatively unloaded area having a certain strength and causing bone tissue to grow quickly.

In order to induce bone regeneration as described above, it is preferable that the bone graft material is biodegradable and is regenerated and absorbed at the same time as the regenerated bone is grown after the bone graft, wherein the bone graft material is more porous if the bone graft material has a pore shape.

Therefore, in the present invention, biodegradable calcium metaphosphate was made of porous ceramics to maximize bone induction. In the present invention, by using a poly urethane (PU) sponge having an open pore of three-dimensional network structure, the surface of the CMP slurry is coated and heat treated at an appropriate temperature so that the sponge is burned out and the pore size of the original sponge has been removed. To prepare a porous CMP ceramics as it is. These porous CMP ceramics can contain other additives to properly control the mechanical strength and biodegradation rate depending on the area used.

The method for producing the biodegradable porous calcium metaphosphate ceramics of the present invention

1) surface modifying the polyurethane polymer sponge;

2) preparing a calcium metaphosphate slurry by mixing calcium metaphosphate powder with water and adding 1-3% by weight of a dispersion stabilizer, 3-7% by weight cracking agent, and 3-7% by weight binder;

3) coating the sponge with calcium metaphosphate and drying by dipping the sponge of step (1) into the calcium metaphosphate slurry of step (2); And

4) A method for producing porous calcium metaphosphate ceramics, comprising the step of sintering and cooling the sponge of step (3).

It consists of stages.

First of all, the ceramic slurry can be adhered well using polyurethane sponge with pores size of 10-80 ppi (pores per inch) as a starting material that provides regular and interconnected pores of three-dimensional network. Modifies the surface to be hydrophilic. For this surface modification, the sponge was soaked in 10% NaOH and then surface treated at 60 ° C. for 25 minutes using an ultrasonic vibrator. Then, to remove NaOH remaining on the surface of the treated sponge, the sponge is immersed in 60 ° C distilled water and washed with an ultrasonic vibrator. Repeat the wash several times to thoroughly clean and dry the sponge, and then measure the basicity with test paper to check the degree of washing.

(Ca (PO ₃ ) ₂ ] _n having a structure of [Ca (PO ₃ ) ₂ ] _n was prepared by calcining at least 510 ° C with Ca (H ₂ PO ₄ ) ₂ .H ₂ O as a starting material. The obtained β-CMP was pulverized in a roller crusher and sieved to prepare CMP powder having a size of 75 μm or less, mixed with water at a weight ratio of 1 to 1, and dispersing agent 4 to stabilize the slurry. Add 1-3% by weight of 4-Amino Benzoic Acid (ABA). To prevent cracking during drying, 3 to 7 wt% of at least one selected from NN-dimethylformamide and tetrahydrofuran (THF) is added, and PVA ( 3 to 7% by weight of at least one selected from polyvinyl alcohol, cellulose, polyvinyl butyral, and dextrin is added to prepare a CMP slurry through a ball milling process.

The sponge prepared in the above process is coated by immersing in the prepared CMP slurry. During coating, the air remaining in the sponge is removed and the shrinkage and expansion of the immersed sponge are repeated several times so that the CMP slurry is well coated on the sponge surface by capillary force. Then, to prevent clogging of pores by the excess slurry present on the sponge surface, the excess slurry is removed by blowing compressed air or passing the sponge between two rollers. The drying rate is maintained by appropriately adjusting the temperature and humidity to prevent the sponge surface microcracking caused by the stress that may occur when drying the sponge coated slurry.

The dried sponge coated with the CMP slurry obtained in the above process is sintered in an electric furnace. Depending on the rate of temperature increase during sintering, the sponge may collapse or the strength may deteriorate. In general, it is possible to shorten the overall sintering time by determining the sintering section during sintering through the TG / DTA analysis results. The first stage of sintering is set at 600 ° C., where the organic additives and polymer sponge are decomposed. At this time, the temperature increase rate is kept slowly at 0.5 ~ 1 ℃ / min to prevent the collapse of the sponge. The second step is to completely remove the residual organic components and the polymer sponge by maintaining the sintering for 30 minutes-2 hours at the reaching temperature of the first step. In the third step, the temperature is raised to 850 ° C. At this time, the temperature can be raised to 3 to 5 ° C / min faster. In the fourth step, the mixture is maintained at 850 ° C. for 2-4 hours and densified in the skeleton, and then cooled slowly to obtain a porous CMP which is a final sintered body.

Since the CMP porous body prepared through the immersion process only once is relatively weak in strength, the immersion process may be performed once again and then resintered to improve the strength. The temperature increase rate at the time of re-sintering is suitable for 3-5 degreeC / min to 850 degreeC, and is made to cool slowly.

Hereinafter, the present invention will be described in more detail with reference to the following examples.

The following examples are merely illustrative of the present invention, and the present invention is not limited by the following examples.

<Example 1> Fabrication of bone graft material consisting of CMP ceramics

(Step 1) Sponge Selection and Surface Treatment

In order to manufacture a bone graft material consisting of CMP having a pore size of 10 ppi, a polyurethane polymer sponge having a pore size of 10 ppi (pores per inch) was selected as a material providing interconnected pores. In order to make the ceramic slurry adhere well because the surface of the selected polyurethane sponge is hydrophobic, the surface was hydrophilicly modified by dipping in 10% NaOH solution at 25 ° C. using an ultrasonic vibrator for 25 minutes. Thereafter, in order to remove NaOH remaining on the surface of the treated sponge, the sponge was immersed in distilled water at 60 ° C. and washed with an ultrasonic vibrator for 25 minutes. The washing process was repeated several times to thoroughly wash the sponge and to dry it. In order to investigate the degree of washing, the basicity was measured by a test paper to confirm that the washing was assured.

(Step 2) CMP slurry preparation (manufacturing)

CMP having a structure of β- [Ca (PO ₃ ) ₂ ] _n was prepared by calcination at 850 ° C. or higher using Ca (H ₂ PO ₄ ) ₂ .H ₂ O as a starting material. The obtained CMP is pulverized in a roller crusher and subjected to a sieving process to prepare a CMP powder having a size of 75 μm or less, mixed with water at a weight ratio of 1 to 1, and 4-ABA as a dispersant to stabilize the slurry. (4-Amino Benzoic Acid) was added 2% by weight. To prevent cracking during drying, 5% by weight of THF (Tetrahydrofuran) was added, and 5% by weight of PVA (Polyvinyl alcohol) was added as a binder, and CMP slurry was prepared through a ball milling process.

(Step 3) CMP slurry coating on polyurethane sponge

The sponge prepared in step 1 was coated by immersing it in the CMP slurry of step 2. During coating, the air remaining in the sponge was removed and the shrinkage and expansion of the immersed sponge were repeated several times so that the CMP slurry was well coated on the sponge surface by capillary force. Then, in order to prevent clogging of pores due to the excess slurry present on the sponge surface, compressed air was injected or the sponge was passed between two rollers to remove the excess slurry. In order to prevent the sponge surface microcracks due to the stress that may occur during drying, the sponge coated slurry was dried at room temperature for 6 hours and then dried at 50 ° C. for 5 hours.

(Step 4) Sinter

In step 3 the dried sponge coated with the CMP slurry was sintered in an electric furnace. The sintering of the sponge may occur depending on the rate of temperature increase during sintering, or the strength may be reduced.

The first step of sintering was up to 600 ° C. in which the organic additives and polymer sponges were decomposed. The temperature increase rate at this time was kept slowly at 0.5 ~ 1 ℃ / min to prevent the collapse of the sponge phenomenon. In the second step, the sintering was maintained at 600 ° C. for 1 hour to completely remove the residual organic component and the polymer sponge. In the third step, the temperature was raised to 850 ° C., at which time the temperature was raised to 3 to 5 ° C./min faster. The fourth step was maintained at 850 ° C. for 3 hours to densify the skeleton, and then cooled slowly to obtain a porous CMP as a final sintered body.

Since the porous CMP block prepared only once through the dipping process is relatively weak in strength, the strength of the porous CMP block can be improved by resintering after performing the dipping process of Step 3 again. The temperature increase rate during resintering was maintained at 3 ~ 5 ℃ / min up to 850 ℃ was cooled slowly.

<Example 2-6> Preparation of bone graft material consisting of CMP of various pore sizes

In the process 1, the pore size of the sponge was changed to 20, 35, 45, 60, 80 ppi to prepare CMP ceramics in the same manner as in Example 1 .

The bone graft material composed of the biodegradable porous calcium metaphosphate (pore size: about 300 μm) of the present invention prepared by the method of Example 1 was implanted into the skull, subcutaneous connective tissue, and muscle tissue of male rabbits to the following Experimental Examples 1 to 3 Tissue response experiments were conducted.

Experimental Example 1 Tissue Response in Subcutaneous Connective Tissues

The bone graft consisting of CMP of the present invention was implanted into the subcutaneous connective tissue, and the results were observed after 4 and 6 weeks.

5A and 5B show photographs taken at 4 and 6 weeks after transplantation of bone grafts consisting of CMP transplanted into male rabbit subcutaneous connective tissue, respectively . Some findings of inflammatory cell infiltration were observed after 4 weeks. 6 weeks after transplantation, inflammatory cells disappeared and bone grafting material composed of CMP was completely fused with subcutaneous connective tissue, and fibroblasts were arranged along the surface of CMP. Shows that connective tissue is invading into the space where the structure is collapsing.

Experimental Example 2 Tissue Response in Muscle Tissue

The bone graft consisting of CMP of the present invention was implanted into the subcutaneous connective tissue, and the results were observed after 4 and 6 weeks.

6A and 6B show photographs taken at 4 and 6 weeks after transplantation of bone grafts composed of CMP transplanted into male rabbit muscle tissue, respectively . Some findings of inflammatory cell infiltration were observed after 4 weeks. 6 weeks after transplantation, the connective tissue layer surrounding CMP was gradually replaced by muscle tissue, and the boundary of CMP became indistinct. Could.

Through Experimental Example 1 and Experimental Example 2, CMP ceramics, the bone graft material of the present invention, was completely fused with subcutaneous connective tissue and muscle tissue, and it was confirmed that the material biodegraded and released from CMP ceramics had no adverse effect on surrounding tissues. .

Experimental Example 3 Tissue Responses of CMP in the Cranial Defects

The bone graft consisting of the CMP of the present invention was transplanted to the skull defect and the control group was formed, and each group was examined 4 and 6 weeks after the transplantation.

As a result, the defects of the control group without the transplantation of CMP-based bone grafts were found to heal most of the fibrous connective tissues after 4 and 6 weeks of surgery. At 6 weeks, some new bones grew from the ends of the defects. It was confirmed that there was.

On the other hand, in the bone graft transplant group composed of CMP , as shown in FIGS. 7A and 7B , most of the defects were filled with connective tissue after 4 weeks of transplantation, and the bone growth was actively progressed while cell proliferation proceeded around the transplanted CMP. 6 weeks after CMP transplantation, new bone actively formed by fusion with transplanted CMP was observed inside the defect. As a result of observing this at high magnification, as shown in FIGS. 8A and 8B , it was confirmed that the new bone was in direct contact with the transplanted CMP and that the deposition occurred. Also, the transplanted CMP was fused with the infiltrated new bone. This was confirmed.

CMP ceramics, a bone graft material of the present invention, is slowly absorbed in bone tissues, subcutaneous connective tissues, and muscle tissues without any foreign body reaction or inflammatory reactions, and shows good compatibility with tissues. It is fused with the organization. Unlike the conventional bone graft hydroxyapatite (HA), which has been proposed and used in the past, the bone marrow response of CMP is considerably different from that in the fibroblasts due to connective tissue intercalation when transplanted into bone defects. This suggests that CMP ceramics have superior bone affinity and bone induction than conventional bone graft materials. These results suggest that CMP is an ideal material with various requirements as an absorbent bone graft material.

Biodegradable porous bone graft material composed of CMP ceramics of the present invention is significantly superior in biosynthesis, bone affinity and bone induction compared to conventional bone graft material, so that it fuses well without any foreign body reaction with tissues of the transplantation site, Decomposed in the human body induces the production of regeneration bone can be usefully used as bone graft material and cell support. In addition, when manufacturing CMP ceramics by the method of summoning a polyurethane sponge as in the present invention, it is possible to easily prepare porous CMP ceramics having a desired pore size by changing the shape of the polyurethane sponge, and thus granular particles having fine pores. It can also be used as a implant for small bone defects such as periodontal lesions.

Claims (10)

Bone graft material or bone cell support composed of biodegradable porous calcium metaphosphate. The bone graft material or osteocyte support according to claim 1, wherein the biodegradable porous calcium metaphosphate is β-phase. Biodegradable porous calcium metaphosphate ceramics for bone graft material or bone cell support mainly composed of calcium metaphosphate. 1) immersed hydrophilic surface-modified polyurethane polymer sponge in calcium metaphosphate slurry, 2) the porous polyurethane polymer sponge coated with calcium metaphosphate slurry is dried after removing the blockage of pores by injection of compressed air or by passing between two rollers; 3) The dried sponge of step (2) was heated to 600 ° C. at a heating rate of 0.5-1 ° C./min, and maintained at 600 ° C. for a time to remove residual organics, components and polymer sponges, and this was 850 ° C. Method of producing calcium metaphosphate ceramics comprising the step of further increasing the temperature and maintaining at 850 ℃ 2-4 hours to densify the skeleton and slow cooling. The method according to claim 4, wherein the steps (1), (2) and (3) are repeated. The method according to claim 4 or 5, wherein the calcium metaphosphate slurry is mixed 1: 1 with calcium metaphosphate powder and water 1-3 wt% dispersion stabilizer, 3-7 wt% crack inhibitor, binder 3-7 A production method characterized by adding a weight%. The surface-modified polyurethane polymer sponge according to claim 4 or 5, wherein the hydrophilic surface-modified polyurethane polymer sponge is treated with a NaOH aqueous solution to surface-modify the polyurethane polymer sponge with hydrophilicity, and the surface-modified polyurethane polymer sponge is A method for producing a product, which is obtained by washing with distilled water. The method of claim 6, wherein the dispersion stabilizer is 4-aminobenzoic acid. The method of claim 6, wherein the crack preventing agent is at least one selected from NN-dimethylformamide and tetrahydrofuran (THF). The method of claim 6, wherein the binder is at least one selected from polyvinyl alcohol (PVA), cellulose, polyvinyl butyral, and dextrin.