KR101094168B1 - Method for preparation of ceramic bone fillers with random shaped surface irregularity - Google Patents

Abstract

The present invention relates to a method for producing a bone conductive ceramic bone filler in which random surface irregularities are introduced by uniformly mixing a thermally decomposable polymer in a cake containing bioactive ceramic powder having bone conductivity. More specifically, the bone conductive ceramic powder is mixed with a solvent to make a slurry, and then filtered to prepare a ceramic cake, which is then mixed with a thermally decomposable polymer prepared in solution to prepare a slime slurry. The slurry is then manufactured to produce bone conductive ceramic bone fillers into which random surface irregularities are introduced through a continuous process of drying, degreasing, sintering, grinding and sieving. The method for producing a bone conductive ceramic bone filler incorporating random surface irregularities according to the present invention is simple in manufacturing method and can easily control the amount of surface irregularities to be introduced.

Ceramic, surface irregularities, pores, granules, bone filler

Description

Method for preparation of ceramic bone fillers with random shaped surface irregularity

The present invention relates to a method for producing a bone filler, and more particularly, to a method for producing a ceramic bone filler is introduced random surface irregularities.

The bone filler is composed of calcium phosphate, calcium sulfate, calcium carbonate, bioglass, and bioglass-ceramic materials, and the bone filler is divided into simple granules or granules having irregularities and pores introduced into the surface of the granules.

A method for producing a bone granule in the form of simple granules is typical of the simple sintering method (US Pat. No. 4,218,255, US Pat. No. 4,693,986, US Pat. No. 5,030,611, and US Pat. No. 5,064,436). In the simple sintering method, the granules are prepared by using the fine powder, and then the granules are manufactured by sintering the granules. By controlling the degree of sintering during the sintering process, micropores or little pores may be introduced into the surface of the granules.

The simple granule form has a high strength of the granule itself but has a relatively small specific surface area compared to the uneven type on which the irregularities are formed on the surface, resulting in a relatively small attachment area of the bone and consequently lowering the mechanical properties of the bone including the same. .

On the other hand, granular bone fillers with surface irregularities and pores are introduced to increase the amount of protein adsorption in the body, as well as the newly generated bone grows in close contact or infiltration with the irregularities and pores on the surface of the bone filler. Increasing the area of attachment can also be expected to increase the mechanical properties of bone, including this. Typical bone fillers range in size from approximately 200 to 1000 μm, and the irregularities introduced to the surface of the granules to increase bone adhesion area are random, with an optimal size in the range of approximately 100 to 400 μm.

Granular bone fillers having surface irregularities introduced are classified into closed, semi-pores, or open pores by the porous shaped bodies used in the manufacturing process.

The most representative method for producing open pore granules is a replica method using a porous polymer sponge (US Pat. No. 4,371,484, US Pat. No. 4,889,833). In the replica method, a porous sponge is impregnated in a bioactive ceramic slurry to apply a slurry on a sponge skeleton, and then the sponge is burned to form a porous body in the process of drying, degreasing and sintering the slurry, and pulverizing the porous body. To prepare an open pore granule of a suitable size. At this time, the continuous pores are formed by the porous sponge skeleton, there is an advantage that can control the size of the continuous pores generated according to the pore size of the porous sponge skeleton used.

However, the open-filled granular bone filler is unsuitable for mass production due to the hassle of impregnating and degreasing the slurry several times in order to obtain granules of the desired strength due to the very low strength compared to the closed-hole granules. There is a disadvantage that the manufacturing cost is increased. In addition, the surface of the granules produced after grinding is very sharp, which is inappropriate for adhesion of bone cells.

In addition to the replica method using a porous sponge, a method used to introduce surface irregularities into or on the surface of granules includes a simple sintering method, a vapor phase temporary method, a solid phase temporary method, and the like.

In the simple sintering method, it is impossible to produce irregularities of 10 μm or more due to the characteristics of the process.

The gas template method is a method of introducing air or a gas generating substance into a high concentration slurry so that the remaining sites remain as pores when sintered, and there is a bubbling method or a foaming method.

The bubbling method (US Pat. No. 5,171,720) is a method of making a high viscosity ceramic slurry and then blowing air to trap air bubbles in the slurry. The bubbling method has a disadvantage in that it is extremely difficult to uniformly disperse and capture bubbles of uniform size by the difference in density between the slurry and the bubbles.

In the foaming method (Japanese Patent Laid-Open No. 7-23994), when a transition metal powder is added in the process of slurrying a raw material, gas generated by an acid or alkali reaction is used or a liquefied gas is used. By introducing pores. Disadvantages of the foaming method can be handled at room temperature when pores are introduced using metal powder, but it is highly likely to cause serious problems in safety if unreacted residues are dissolved in the body. In addition, even in the case of using a liquefied gas such as freon gas, most of them are environmental pollutants and due to the low liquefaction temperature, the handling temperature of the slurry must be lowered, thereby increasing the process cost.

In addition, in the solid template method, the surface irregularities of the granules such as the pore size and distribution depend on the characteristics of the solid phase temporary agent, that is, the size and distribution of the solid phase temporary agent. In order to be satisfied, the selection of an appropriate solid phase agent is important. In this case, a method of using polymer beads for controlling pore size has been reported [US Pat. No. 4,777,153]. At this time, a manufacturing cost increases because a bead on demand is used to arbitrarily adjust the pore size. . In addition, since the solid beads do not shrink during drying of the slurry, many cracks are generated in the bulk body and distortion is caused.

Therefore, in order to solve the problems in the current manufacturing process it is necessary to develop a new type of bone filler manufacturing method.

The technical problem to be solved by the present invention is to provide a method for producing a bone filler and a bone filler excellent in economics and reproducibility by a simple manufacturing method and easily controlling the amount of surface irregularities are introduced.

In order to solve the above technical problem, a bone filler manufacturing method according to the present invention comprises the steps of mixing a ceramic cake made of a bone conductive material and a thermally decomposable polymer solution to form a slurry; And forming a bone filler having irregularities of random size and shape from the slurry.

In the bone filling material manufacturing method according to the present invention, the step of forming a bone filling material in which random irregularities are introduced from the slurry, drying the slurry to form a molded body; Degreasing and then sintering the molded body to form a porous molded body; And sieving the porous formed body after pulverization.

In the bone filling material manufacturing method according to the present invention, the bone conductive material may be at least one of a calcium phosphate-based compound, calcium sulfate-based compound, calcium carbonate-based compound, bioglass and bioglass-ceramic.

In the bone filling material manufacturing method according to the present invention, the calcium phosphate compound may be a mixture of a non-degradable calcium phosphate compound and a biodegradable calcium phosphate compound.

In the bone filling material manufacturing method according to the present invention, the biodegradable calcium phosphate compound may be 20 to 50% by weight relative to the non-degradable calcium phosphate compound.

In the bone filling material manufacturing method according to the present invention, the calcium phosphate compound is apatite (apatite), tricalcium phosphate (TCP), calcium metaphosphate (CMP), amorphous calcium phosphate (ACP), calcium monophosphate (brushite), It may be one or more selected from the group consisting of octacalcium phosphate (OCP) and tetracalcium phosphate (TTCP).

In the method for preparing bone filler according to the present invention, the thermally decomposable polymer solution is polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, guar gum, polyacrylate in an aqueous solvent. At least one selected from the group consisting of polyvinylpyrrolidone, polyethylene oxide and polymethylstyrene may be dissolved.

In the method for preparing bone filler according to the present invention, the thermally decomposable polymer solution is one selected from the group consisting of polyvinylbutylene, polyethylene, polypropylene, polycaprolactone, polylactic cordylic acid and polysulfone in an organic solvent. The above may be dissolved.

In the bone filling material manufacturing method according to the present invention, the thermally decomposable polymer solution may be dissolved 5 to 30% by weight of the thermally decomposable polymer with respect to the solvent.

In the bone filling material manufacturing method according to the invention, the thermally decomposable polymer solution may be 100 to 500% by weight based on the ceramic cake.

In order to solve the above technical problem, the bone filler according to the present invention is manufactured by the above method is formed with irregularities on the surface.

The size of the bone filler according to the invention may be 200 ~ 5000 μm.

According to the present invention, it is possible to produce a bone filler with a very high surface irregularities by a simple method. As the surface irregularities of the bone filler increases, the specific surface area increases, so that the bone conductivity is dramatically increased, and by adding an appropriate amount of tricalcium phosphate, it is possible to easily prepare the bone filler whose biodegradability is controlled.

Hereinafter, with reference to the accompanying drawings will be described in detail with respect to the ceramic bone filler manufacturing method introduced random surface irregularities according to the present invention and a preferred embodiment of the bone filler prepared by this method. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in various forms, and only the present embodiments are intended to complete the disclosure of the present invention and to those skilled in the art to fully understand the scope of the invention. It is provided to inform you.

1 is a flow chart showing a preferred process for the bone filler manufacturing method according to the present invention.

Referring to Figure 1, the bone filler manufacturing method according to the present invention, first, to prepare a ceramic cake made of a bone conductive material (S110). Step S110 is to synthesize a ceramic powder made of a bone conductive material in an aqueous solution or mix the synthesized powder with a solvent, and then filter to prepare a ceramic cake. In the ceramic cake, the bone conductive material is prepared at a high concentration so as to be 70 to 99% by weight of the total, and preferably, the ceramic cake is prepared to be 80 to 95% by weight.

The ceramic powder made of a bone conductive material may be made of calcium phosphate-based compound, calcium sulfate-based compound, calcium carbonate-based compound, bioglass, bioglass-ceramic, or a combination thereof. Calcium phosphate compounds include apatite, tricalcium phosphate (TCP), calcium metaphosphate (CMP), amorphous calcium phosphate (ACP), calcium monophosphate (brushite), octacalcium phosphate (OCP) and tetracalcium phosphate (TTCP). It may be one or more selected from the group consisting of. The calcium phosphate compound may be a mixture of a non-degradable calcium phosphate compound and a biodegradable calcium phosphate compound. Preferably, a mixture of apatite hydroxide and tricalcium phosphate is used. The biodegradable calcium phosphate compound is used in an amount of 10 to 60% by weight, preferably 20 to 50% by weight based on the non-degradable calcium phosphate compound.

The solvent may be an aqueous solvent or an organic solvent. It is preferable to use ion-exchange water as an aqueous solvent, and all organic solvents can be used as an organic solvent, Among these, alcohols are preferable.

Next, a thermally decomposable polymer solution is prepared (S120). Thermally decomposable polymers are used to form random surface irregularities. As a solvent for preparing the thermally decomposable polymer solution, an aqueous solvent or an organic solvent is used.

When an aqueous solvent is used, the thermally decomposable polymer may be polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, guar gum, polyacrylate, polyvinylpyrrolidone, polyethylene oxide. , Polymethylstyrene and combinations thereof are used. In the case where an organic solvent is used, the thermally decomposable polymer is polyvinyl butylene, polyethylene, polypropylene, polycaprolactone, polylactic codicolic acid, polysulfone, and combinations thereof.

In preparing the thermally decomposable polymer solution, a thermally decomposable polymer having a range of 5 to 30% by weight relative to the solvent is dissolved in the solvent, and preferably 10 to 15% by weight of the thermally decomposable polymer solvent is dissolved.

Next, a slurry is formed by mixing the ceramic cake prepared in step S110 and the thermally decomposable polymer solution prepared in step S120 (S130). In order to form a homogenized slurry, the ceramic cake and the thermally decomposable polymer solution are mixed and then sufficiently stirred. The amount of the conductive polymer solution to be mixed to form the slurry is 100 to 500% by weight, preferably 200 to 400% by weight based on the ceramic cake.

Next, the slurry formed in step S130 is dried to form a molded body (S140). Step S140 is to dry in an oven having a temperature range of 30 ~ 100 ℃, more preferably carried out in a temperature range of 50 ~ 80 ℃, to completely dry the slurry.

Then, the molded body is degreased (S150). "Degreasing" in the present invention means to remove the organic component by maintaining the molded body formed in step S140 for a predetermined time in a furnace having a temperature range of 400 ~ 800 ℃. Preferably, step S150 is carried out in a temperature range of 500 ~ 700 ℃, the time may vary depending on the temperature range, but usually proceeds for 1 to 3 hours.

Further heating the molded body degreased in a continuous manufacturing process to sinter in a temperature range of 900 ~ 1300 ℃ to form a porous molded body (S160). Depending on the temperature range, the sintering time may vary, typically 2 to 5 hours. Preferably it is carried out for 3 hours at a temperature range of 1100 ~ 1300 ℃ to form a porous molded body.

And after crushing the porous molded body, sifted to prepare a bone filler having a size in the range of 200 ~ 5000 μm, the random surface irregularities are formed (S170).

Since the present invention adopts a relatively simple method of forming, drying, degreasing, sintering, pulverizing and sieving the slurry, it is possible to mass produce a product having high reliability. In the bone filler of the present invention, by introducing a random surface irregularities of the appropriate size, the bone adhesion area is increased compared to the simple granular bone filler, and the newly generated bone tissue is easily inside or on the surface of the porous body of the bone filler. It can grow strongly and be combined strongly. And mechanical strength is improved compared to the bone filling material which is completely open pore type.

And when using a ceramic cake in which non-degradable and biodegradable calcium phosphate is mixed, bone conduction and biodegradability can be easily controlled.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the examples.

Example  1: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacturing 1

Apatite hydroxide (hydroxyapatite) and tricalcium phosphate (β-tricalcium phosphate) were synthesized by themselves using a known liquid phase reaction method, and then filtered and then ceramic cake mixed with 24.6 g of apatite hydroxide and 16.4 g of tricalcium phosphate. 41 g (apatite hydroxide: tricalcium phosphate = 60: 40) was prepared. Thereafter, 2.6 g of polyvinyl alcohol having a molecular weight of 146,000 to 186,000 was completely dissolved in 100 g of ion-exchanged water to prepare a thermally decomposable polymer solution (2.5% by weight polyvinyl alcohol solution). And it was mixed with the prepared apatite hydroxide / tricalcium phosphate ceramic cake to prepare 143.6 g of a mucus apatite hydroxide / tricalcium phosphate slurry.

This slurry was then completely dried in an oven at 60 ° C. to form a molded body. After degreasing at 600 ° C. for 2 hours in muffle furnace, and sintering at 1100 ° C. for 3 hours to obtain a porous apatite hydroxide / tricalcium phosphate composite. And after pulverizing the porous apatite hydroxide / tricalcium phosphate complex was sifted to prepare a bone filler in the form of apatite hydroxide / tricalcium phosphate granules containing random surface irregularities of 200 ~ 1000 μm size, the results are shown in Figure 2 It was.

Example  2: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 2

All procedures were performed in the same manner as in Example 1 except that 5.3 g of polyvinyl alcohol was dissolved in 100 g of ion-exchanged water to prepare a thermally decomposable polymer solution (5.0% by weight of polyvinyl alcohol). The bone filler in the form of apatite hydroxide / tricalcium phosphate granules was prepared, and the results are shown in FIG. 3.

Example  3: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacturing 3

All procedures were performed in the same manner as in Example 1 except that 8.1 g of polyvinyl alcohol was dissolved in 100 g of ion-exchanged water to prepare a thermally decomposable polymer solution (7.5% by weight of polyvinyl alcohol). The bone filler was prepared in the form of apatite hydroxide / tricalcium phosphate granules, and the results are shown in FIG.

Example  4: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacturing 4

All procedures were performed in the same manner as in Example 1 except that 11.1 g of polyvinyl alcohol was dissolved in 100 g of ion-exchanged water to prepare a thermally decomposable polymer solution (10.0 wt% solution of polyvinyl alcohol). The bone filler was prepared in the form of apatite hydroxide / tricalcium phosphate granules, and the results are shown in FIG. 5.

Example  5: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 5

All procedures were performed in the same manner as in Example 1 except that 13.6 g of polyvinyl alcohol was dissolved in 100 g of ion-exchanged water to prepare a thermally decomposable polymer solution (12.0 wt% solution of polyvinyl alcohol). The bone filler was prepared in the form of apatite hydroxide / tricalcium phosphate granules, and the results are shown in FIG. 6.

Example  6: Apatite Hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 6

Except for preparing 41 g of ceramic cake (apatite hydroxide: tricalcium phosphate = 100: 0) made of apatite hydroxide, all the processes were performed in the same manner as in Example 5, except for apatite hydroxide / tricalcium phosphate containing random surface irregularities. A bone filler in the form of granules was prepared.

Example  7: Apatite Hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 7

All procedures were performed in the same manner as in Example 5 except that 41 g of ceramic cake (apatite hydroxide: tricalcium phosphate = 80: 20) containing 32.8 g of apatite hydroxide and 8.2 g of tricalcium phosphate was prepared. Apatite hydroxide / tricalcium phosphate granules including bone filler was prepared.

Example  8: Apatite Hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 8

All procedures were performed in the same manner as in Example 5, except that 41 g of ceramic cake (apatite hydroxide: tricalcium phosphate = 40: 60) containing 16.4 g of apatite hydroxide and 24.6 g of tricalcium phosphate was prepared. Apatite hydroxide / tricalcium phosphate granules including bone filler was prepared.

Example  9: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 9

All procedures were performed in the same manner as in Example 5 except that 41 g of ceramic cake (apatite hydroxide: tricalcium phosphate = 20: 80) containing 8.2 g of apatite hydroxide and 32.8 g of tricalcium phosphate was prepared. Apatite hydroxide / tricalcium phosphate granules including bone filler was prepared.

Example  10: apatite hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 10

Except for preparing 41 g of a ceramic cake made of tricalcium phosphate (apatite hydroxide: tricalcium phosphate = 0: 100), all the processes were performed in the same manner as in Example 5, except that the apatite hydroxide / ginseng phosphate containing random surface irregularities A bone filler in the form of calcium granules was prepared.

Example  11: Apatite Hydroxide / Tricalcium phosphate  Used Random  Biodegradable Bone with Surface Unevenness Filling  Manufacture 11

Except for the use of ethyl alcohol instead of ion-exchanged water and polyvinylbutylene instead of polyvinyl alcohol, all procedures were performed in the same manner as in Example 5 to obtain bone fillers in the form of apatite hydroxide / tricalcium phosphate granules containing random surface irregularities. Prepared.

Comparative example  1: apatite hydroxide / Tricalcium phosphate  Used bone Filling  Produce

A bone filler in the form of apatite hydroxide / tricalcium phosphate granules was prepared in the same manner as in Example 1 except that only 100 g of ion-exchanged water was mixed with a ceramic cake without adding polyvinyl alcohol. The results are shown in FIG.

Table 1 summarizes the mixing conditions of Examples 1 to 10 and Comparative Example 1.

Example In total pyrolytic polymer solution
Amount of polyvinyl alcohol (wt%) Apatite Hydroxide: Tricalcium Phosphate
(Weight ratio) Example 1 2.5 60: 40 Example 2 5.0 60: 40 Example 3 7.5 60: 40 Example 4 10.0 60: 40 Example 5 12.0 60: 40 Example 6 12.0 100: 0 Example 7 12.0 80: 20 Example 8 12.0 40: 60 Example 9 12.0 20: 80 Example 10 12.0 0: 100 Comparative Example 1 0 60: 40

Surface roughness, biodegradability and bone conductivity were measured to evaluate the properties of the bone filler prepared by the method of Examples 1 to 11.

After measuring the specific surface area of the specimen by using BET, the surface unevenness is 'small' if the specific surface area value is 5 m2 / g or less, 'medium' if 5 to 10 m2 / g and more than 10 m2 / g. Evaluated as 'large'. Biodegradability and bone conductivity test is to form a circular defect with a diameter of 11mm in the skull of the Australian white male rabbit, and then each bone bone filling material prepared by the method of Examples 5 to 8 were embedded and sacrificed after 4 weeks to make a tissue specimen It evaluated by the optical microscope. In this case, the results of bone conduction are 'small' when the new bone occupies 0-15% of the total bone defect area, 'medium' when 15-30%, and 'great' when 30% or more. Evaluated as. The biodegradability test evaluated 'large' when the residual area of bone filler was 30% or less, 'medium' when 30 to 70%, and 'small' when 70% or more. Table 2 shows the results of evaluating surface roughness, biodegradability and bone conductivity.

Example Surface unevenness (specific surface area) Biodegradability Bone conductivity Example 1 small medium small Example 2 small medium small Example 3 medium medium medium Example 4 medium medium medium Example 5 versus medium versus Example 6 versus small small Example 7 versus small medium Example 8 versus versus medium Example 9 versus versus small Example 10 versus versus small Example 11 versus medium versus Comparative Example 1 small small small

Referring to Tables 1 and 2, the surface roughness (specific surface area) of the bone filler was proportional to the amount of the thermally decomposable polymer, and the results of observing them with an optical microscope (FIGS. 2 to 6) showed that the size and shape of the surface irregularities were It was confirmed that it was formed randomly. On the other hand, as a result of evaluating bone conductivity and biodegradation using them, it can be seen that the bone conductivity increased in proportion to the surface irregularities of the bone filler, the biodegradability increased in proportion to the addition amount of tricalcium phosphate (Fig. 8). And FIG. 9).

On the other hand, the bone filler prepared by the method of Comparative Example 1, the surface irregularities, biodegradability and bone conductivity was very low (Fig. 10).

As a result, the present invention can control the introduction amount of random surface irregularities by appropriately changing the amount of the thermally decomposable polymer used in the manufacturing process, it is possible to control the biodegradability by changing the addition amount of tricalcium phosphate Biodegradable bone fillers having good bone conductivity and introducing biodegradable randomized surface irregularities can be prepared.

Although the preferred embodiments of the present invention have been shown and described above, the present invention is not limited to the specific preferred embodiments described above, and the present invention belongs to the present invention without departing from the gist of the present invention as claimed in the claims. Various modifications can be made by those skilled in the art, and such changes are within the scope of the claims.

1 is a flow chart showing a preferred process for the bone filler manufacturing method according to the present invention.

Figure 2 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler containing random surface irregularities prepared by the method of Example 1.

Figure 3 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler containing random surface irregularities prepared by the method of Example 2.

Figure 4 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler containing random surface irregularities prepared by the method of Example 3.

Figure 5 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler containing random surface irregularities prepared by the method of Example 4.

Figure 6 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler containing random surface irregularities prepared by the method of Example 5.

7 is an optical micrograph of the surface of the apatite hydroxide / tricalcium phosphate composite bone filler prepared by the method of Comparative Example 1.

FIG. 8 is an optical micrograph of a tissue specimen sacrificed 4 weeks after the bone filling material prepared by the method of Example 5 was formed after forming a circular defect having a diameter of 11 mm in the skull of an Australian male rabbit.

FIG. 9 is an optical micrograph of a tissue specimen sacrificed 4 weeks after implanting a bone filler prepared by the method of Example 8 after forming a circular defect having a diameter of 11 mm in the skull of an Australian male rabbit.

FIG. 10 is an optical micrograph of a tissue specimen sacrificed 4 weeks after embedding a bone defect prepared by the method of Comparative Example 1 after forming a circular defect having a diameter of 11 mm in the skull of an Australian male rabbit.

Claims (12)

Mixing a ceramic cake made of a bone conductive material with a thermally decomposable polymer solution to form a slurry; And Forming a bone filler having irregularities of random size and shape from the slurry; The thermally decomposable polymer solution is 5 to 30% by weight of the thermally decomposable polymer is dissolved in the solvent, the thermally decomposable polymer solution is characterized in that the bone filler material manufacturing method characterized in that 100 to 500% by weight relative to the ceramic cake. The method of claim 1, Forming a bone filler is introduced random random irregularities from the slurry, Drying the slurry to form a compact; Degreasing and then sintering the molded body to form a porous molded body; And And sieving the porous formed body after pulverization. The method of claim 1, The bone conducting material is a bone phosphate-based compound, calcium sulfate-based compound, calcium carbonate-based compound, bioglass and bioglass-ceramic manufacturing method of bone filler characterized in that at least one of. The method of claim 3, The calcium phosphate compound is a bone filler manufacturing method characterized in that the non-degradable calcium phosphate compound and the biodegradable calcium phosphate compound is mixed. 5. The method of claim 4, The biodegradable calcium phosphate compound is a bone filler manufacturing method, characterized in that 20 to 50% by weight relative to the non-degradable calcium phosphate compound. The method of claim 3, The calcium phosphate compounds include apatite, tricalcium phosphate (TCP), calcium metaphosphate (CMP), amorphous calcium phosphate (ACP), calcium monophosphate (brushite), octacalcium phosphate (OCP) and tetracalcium phosphate ( TTCP) bone filling method characterized in that at least one selected from the group consisting of. The method of claim 1, The thermally decomposable polymer solution is polyvinyl alcohol, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, guar gum, polyacrylate, polyvinylpyrrolidone, polyethylene oxide and poly Method for producing a bone filler, characterized in that one or more selected from the group consisting of methyl styrene is dissolved. The method of claim 1, The thermally decomposable polymer solution is a bone filler characterized in that one or more selected from the group consisting of polyvinyl butylene, polyethylene, polypropylene, polycaprolactone, polylactic codlic acid and polysulfone are dissolved in an organic solvent. Manufacturing method. delete delete delete delete

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