KR101981704B1 - Method of manufacturing porous ceramic scaffolds using freeze casting and porous ceramic scaffolds manufactured thereby - Google Patents

Abstract

The present invention relates to a method for manufacturing a porous ceramic support using a freeze casting method and a porous ceramic support produced thereby. More particularly, the present invention relates to a process for producing a core-shell type porous ceramic support having an inner pore size and an outer pore size larger than the outer pore size by preparing an inner porous body by a freeze casting method, And a porous ceramic support prepared thereby. Accordingly, the present invention is structurally similar to bone, and since the bone-active ceramic is used as a ceramic powder, it has high biocompatibility, and cell proliferation can be smoothly performed, so that it can be suitably used as a bone support.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a method for manufacturing a porous ceramic support using a freeze casting method, and a porous ceramic support prepared by the method. BACKGROUND ART < RTI ID = 0.0 >

The present invention relates to a method for manufacturing a porous ceramic support using a freeze casting method and a porous ceramic support produced thereby. More particularly, the present invention relates to a method for manufacturing a porous ceramic support having different pore sizes, both inside and outside, by a freeze casting method, and to a porous ceramic support manufactured thereby.

Porous supports are widely used in many fields due to their excellent mechanical properties. A representative field of bone tissue engineering is bio-artificial bone, which is used as a material that is injected into the body to replace the bones of human body damaged by diseases or accidents. Bio-artificial bones are injected into the body to promote early bone cell deposition and differentiation, ultimately leading to rapid bone formation.

Bioactive ceramics such as hydroxyapatite (HA) and? -Tricalcium phosphate (? -TCP) are widely used as bioactive ceramic materials satisfying these conditions. In addition, for the porous support to be used in the field of bone tissue engineering, it should be structurally three-dimensionally interconnected macroscopic double-pore structure and porous with sufficient strength. Process technologies such as replica, sacrificial template, and direct foam have been reported for the production of porous ceramics. However, since they have inherent advantages and disadvantages, it is difficult to satisfy the structural requirements of the bone tissue engineering support only by the application of a single process.

Among the process technologies for the production of porous ceramics, gel casting as a wet-forming process has advantages of uniform microstructure, near net-shape, complicated shape parts and high strength, And is widely used for manufacturing. Gel casting, which is a direct solidification method, can convert the slurry fluid directly into a rigid body without removing the liquid phase, thereby overcoming problems such as drying shrinkage that may occur in a conventional wet process. At this time, the solids content of the slurry is directly related to the molding strength, drying and plastic contraction, so that a high concentration (> 50%) suspension is required in the gel casting in order to bring it closer to the required dimensions of the ceramic parts. For this reason, gel casting has generally been recognized as a process technology for the production of shaped bodies having a high density, but can also be used for the production of porous ceramics by introducing pore forming materials.

However, the gel casting is disadvantageous in that if the molding density is too low, significant shrinkage occurs in the volatilization process of the organic material, so that the porosity obtained by gel casting is usually limited to less than 60%. In addition, although the gel casting of the foam enables the production of a ceramic support having high strength, there is a problem that the size of pores usually obtained is too small, and heterogeneous and almost no structure having pore mesh connected to each other can be made.

Freeze casting (or freeze drying) has been reported with another wet forming technique for making porous ceramics. This technique includes slip fabrication, freezing, sublimation drying, calcination, and sintering processes. The frozen solvent acts as a template for temporary binder and pore channels between the powder particles and is connected to one another in a dendritic structure in which the crystals of the solvent are surrounded by a frozen ceramic slurry. Removal of the solvent by sublimation can minimize dry stress and shrinkage which can lead to defects such as cracking or distortion that can occur during normal drying. The final microstructure is dependent on lyophilization and sintering conditions, and pore channels and pore gradients with orientation can be obtained by controlling the freezing direction and temperature gradient.

However, in the freeze casting process, the ultra-porous formed body obtained when the freeze suspension is sublimated due to low molding strength has a problem that it is very weak to be difficult to handle. In addition, the pore size obtained by this method is not more than several tens of micrometers, which is not enough to be used as a bone tissue engineering support.

Korea Patent Publication No. 10-2011-0088903

The present invention has been made in view of the above problems, and it is an object of the present invention to provide a porous ceramic body having a structure similar to a bone and having a pore size different from that of the inside and the outside and having a pore size of several tens of micrometers or more, It is an object of the present invention to provide a method for producing a support and a porous ceramic support produced thereby.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are not intended to limit the invention to the precise form disclosed. There will be.

According to an aspect of the present invention, there is provided a method of preparing a ceramic slurry, comprising: preparing a first slurry by mixing a first ceramic powder, a first freezing medium, and a first dispersant; Preparing a second slurry by mixing the first slurry and the second slurry; preparing a second slurry by mixing the first slurry and the second slurry to produce a first freeze-molded body by freezing the slurry; freezing the second slurry on the surface of the first freeze- Preparing a core shell freeze-molded body, removing the first freeze medium and the second freeze medium from the core-shell freeze-molded body to prepare a core-shell porous article, and heat-treating the core-shell porous article And the pore size of the first freeze-molded body is larger than the pore size of the second freeze-molded body.

In the embodiment of the present invention, the pore size of the first freeze-molded body is controlled by the content ratio of the first ceramic powder and the first freezing medium, and the pore size of the second freeze- Freezing medium. The present invention is also directed to a method for preparing a porous ceramic support.

In an embodiment of the present invention, the first ceramic powder or the second ceramic powder may be at least one selected from the group consisting of hydroxyapatite (HA), alpha-tricalcium phosphate (alpha-TCP), beta -tricalcium phosphate (TTCP), amorphous calcium phosphate (ACP), monocalcium phosphate anhydrate (MCPA), dicalcium phosphate (MCPA), and anhydrous calcium phosphate anhydrous DCPD, octacalcium phosphate (OCP), monocalcium phosphate monohydrate (MCPM), dicalcium phosphate dehydrate (DCPD), Na ₂ O-CaO-SiO ₂ - Wherein the porous ceramic support comprises at least one selected from the group consisting of P ₂ O ₅ , CaOSiO ₂ , P ₂ O ₅ -CaO-Na ₂ O and P ₂ O ₅ -CaO-K ₂ O May be .

In an embodiment of the present invention, the first freezing medium or the second freezing medium is selected from the group consisting of water, Camphene, Camphor, naphthalene, and terpenoid-based materials Wherein the porous ceramic support comprises at least one of the following materials:

In an embodiment of the present invention, the first dispersant or the second dispersant may be an oligomeric polyester.

In an embodiment of the present invention, the weight of the first freezing medium may be 100 wt% to 500 wt% of the first ceramic powder, based on 100 wt% of the first ceramic powder.

In the embodiment of the present invention, the weight of the first dispersant may be 0.1 wt% to 10 wt%, based on 100 wt% of the first ceramic powder.

In an embodiment of the present invention, the weight of the second freezing medium is 30 wt% to 100 wt% based on 100 wt% of the second ceramic powder.

In an embodiment of the present invention, the weight of the second dispersant may be 0.1 wt% to 10 wt%, based on 100 wt% of the second ceramic powder.

In the embodiment of the present invention, the step of preparing the first freeze-molded body may be performed at a temperature below the freezing temperature of the first freezing medium.

In an embodiment of the present invention, in the step of manufacturing the first freeze-molded body, the first slurry is injected into the first mold, and is rotated and cooled.

According to an embodiment of the present invention, the step of preparing the core-shell freeze-molded body may be performed at a temperature below the freezing temperature of the second freezing medium.

In the embodiment of the present invention, in the step of manufacturing the core-shell freeze-molded body, the second slurry is injected into the second mold, and is rotated and cooled.

In an embodiment of the present invention, the first slurry is injected into a first mold, the second slurry is injected into a second mold to be rotated and cooled, and the size of the first mold is larger than the size of the second mold The porous ceramic substrate may be a porous ceramic substrate.

In an embodiment of the present invention, further comprising the step of growing the granules of the first freezing medium and the second freezing medium between the step of producing the core-shell freeze-molded article and the step of producing the core-shell porous article Wherein the porous ceramic substrate is a porous ceramic substrate.

In the embodiment of the present invention, the step of heat-treating the core-shell porous body may be performed in a vacuum state at a temperature ranging from 1100 ° C to 1400 ° C.

According to another aspect of the present invention, there is provided a porous ceramic support manufactured by a method for manufacturing a porous ceramic support.

According to another aspect of the present invention, there is provided a bone support comprising a porous ceramic support.

According to another aspect of the present invention, there is provided a method of manufacturing a core-freeze-molded article having a pore size of 120 μm to 185 μm and a shell freezing step having a pore size of 30 μm to 60 μm formed on the surface of the core- And a porous ceramic support having a porosity of 30% to 75%.

In an embodiment of the present invention, the porosity of the core-freeze-molded body may be 60% to 75%.

In an embodiment of the present invention, the porosity of the shell freeze-molded body may be 20% to 30%.

In an embodiment of the present invention, the core-freezing compact may have a diameter of 5 mm to 18 mm.

In an embodiment of the present invention, the shell freeze-molded body may have a diameter of 10 mm to 36 mm.

As one effect of the present invention, a porous ceramic support having different pore sizes, both inside and outside, can be manufactured by the freeze casting method.

At this time, the pore size can be controlled according to the content ratio of the ceramic powder and the freezing medium in the slurry for preparing the porous ceramic support, and as the concentration of the ceramic powder in the slurry is higher, the pore size becomes smaller, , And the lower the concentration of ceramic powder, the larger the pore size, and the cancellous bone structure can be exhibited. Thus, the porous ceramic support is similar to the bone structure and thus may be suitable for use as a bone support.

As another effect of the present invention, the porous ceramic support has a high biocompatibility because the bone activated ceramic is used as a ceramic powder, and cell proliferation can be smoothly performed.

In addition, since the pore size of the hamate bone structure of the porous ceramic support manufactured by the above-mentioned freeze casting method is 100 μm or more, it may be suitable for use as a bone graft material.

It should be understood that the effects of the present invention are not limited to the above effects and include all effects that can be deduced from the detailed description of the present invention or the configuration of the invention described in the claims.

1 is a flowchart illustrating a method of manufacturing a porous ceramic support according to an embodiment of the present invention.
FIG. 2 is a schematic view illustrating a process of fabricating a porous ceramic support according to an embodiment of the present invention. Referring to FIG.
3 is a micro-CT image showing the bone support of Preparation Example 1 according to an embodiment of the present invention.
4 is an image of a surface scanning microscope showing the inside of a bone support of Production Example 1 according to an embodiment of the present invention.
FIG. 5 is a micro-CT image showing a cross-section of a bone support according to an area ratio of the first freeze-molded body and the second freeze-molded body according to an embodiment of the present invention.
6 is a graph showing the compressive strength of a bone support according to the area ratio of the first freeze-molded body and the second freeze-molded body according to an embodiment of the present invention.
7 is a light microscope image showing cells attached to the outside of the bone support of Comparative Example 2 (Fig. 7 (A)) and Production Example 1 (Fig. 7 (B)).
8 is a graph showing cell proliferation results of the bone support of Comparative Example 2 and Preparation Example 1 according to an embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout the specification, when a part is referred to as being "connected" (connected, connected, coupled) with another part, it is not only the case where it is "directly connected" "Is included. Also, when an element is referred to as " comprising ", it means that it can include other elements, not excluding other elements unless specifically stated otherwise.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, the terms "comprises" or "having" and the like refer to the presence of stated features, integers, steps, operations, elements, components, or combinations thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Hereinafter, a method for manufacturing a porous ceramic support will be described.

1 is a flowchart illustrating a method of manufacturing a porous ceramic support according to an embodiment of the present invention. Referring to FIG. 1, the porous ceramic support manufacturing method includes preparing a first slurry by mixing a first ceramic powder, a first freezing medium, and a first dispersing agent (S100), a second ceramic powder, a second freezing medium, (S300) of preparing a first slurry by mixing the second dispersant (S200), freezing and casting the first slurry (S300), forming the second slurry on the surface of the first freeze- Preparing a core-shell porous article by removing the first freezing medium and the second freezing medium from the core-shell freeze-molded article (step S400) S500) and heat treating the core-shell porous body (S600).

FIG. 2 is a schematic view showing a process of manufacturing a porous ceramic support. FIG. 2 is a cross-sectional view schematically showing a process of preparing a porous ceramic support by injecting a first slurry into a first mold, followed by lyophilization To thereby prepare a first frozen formed body (Fig. 2 (B)). After the first freeze-molded body is placed in a second mold having a diameter larger than that of the first mold, the second slurry is injected into the empty space between the first freeze-molded body and the second mold and lyophilized (FIG. Thereafter, the second mold is removed to produce a second freeze-molded body to produce a core-shell freeze-molded body (FIG. 2 (D)), and the first freezing medium and the second freezing medium are removed from the core- (Fig. 2 (E)) of producing a porous ceramic support and heat-treating the core-shell porous article to produce a porous ceramic support.

First, in the step (S100) of preparing the first slurry by mixing the first ceramic powder, the first freezing medium and the first dispersing agent, since the first slurry must be prepared in a state of good fluidity, Lt; / RTI > temperature.

The first ceramic powder may be selected from the group consisting of hydroxyapatite (HA), alpha-tricalcium phosphate (alpha-tricalcium phosphate), and the like. , α-TCP), β-tricalcium phosphate, tetracalcium phosphate (TTCP), amorphous calcium phosphate (ACP), monocalcium phosphate anhydrate , MCPA), dicalcium phosphate anhydrate (DCPD), octacalcium phosphate (OCP), monocalcium phosphate monohydrate (MCPM), dicalcium phosphate dehydrate (DCPD) ), Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ , CaOSiO ₂ , P ₂ O ₅ -CaO-Na ₂ O and P ₂ O ₅ -CaO-K ₂ O, You can include it. , It specifies that not limited to this.

For example, the first ceramic powder may be hydroxyapatite.

The first freezing medium is not particularly limited as long as the energy required for removing the first freezing medium in step S500 of manufacturing a core-shell porous body described later is not excessive. Preferably, the first freezing medium may include at least one selected from the group consisting of water, Camphene, Camphor, naphthalene and terpenoid, But is not limited thereto. In particular, the camphin can be used as a first freezing medium because the freezing temperature is 35 ° C to 45 ° C and can easily be evaporated and removed at room temperature to improve the energy efficiency in producing the porous ceramic support of the present invention .

The first dispersing agent serves to disperse the first ceramic powder in the first freezing medium, and may be used without limitation as long as it can be easily dried and evaporated. Specifically, an oligomeric polyester may be used as the first dispersant.

Meanwhile, in step S100, the content ratio of the first ceramic powder and the first freezing medium may be adjusted in order to control mechanical properties such as porosity, pore size and compressive strength of the first frozen formed body to be manufactured later .

Since the porous ceramic support may exhibit a structure similar to that of a bone, it may be similar to a compact bone structure surrounding the cancellous bone. Accordingly, the porous body portion of the first freeze-molded body portion after removing the first freezing medium can be manufactured to have a large pore size, which is a cancellous bone structure. More specifically, the pore size of the porous article of the first freeze-molded article portion after the removal of the first freeze medium can be adjusted within the range of 120 μm to 185 μm, and the porosity can be adjusted within the range of 60% to 75%. Therefore, in order to produce the porous article having the above-described pore size and porosity, the weight of the first freezing medium may be 100 wt% to 500 wt%, more preferably 120 wt% % To 200% by weight may be suitable. If the weight of the first freezing medium is less than 100% by weight of the first ceramic powder, the amount of the first ceramic powder may be insufficient to remove the first freezing medium from the porous ceramic support So that it is difficult to form a structure. When the weight of the first freezing medium is more than 500 wt% of the first ceramic powder, the first slurry is not preferable because it is difficult to have a proper viscosity because the first slurry is made into a later-prepared first freeze- .

The weight of the first dispersant may be 0.1 wt% to 10 wt%, more preferably 0.5 wt% to 2 wt%, based on 100 wt% of the first ceramic powder. When the weight of the first dispersant is less than 0.1 wt% based on 100 wt% of the first ceramic powder, the ceramic powder may aggregate to form a first slurry having a uniform composition, which is not preferable. If the weight of the first dispersant is more than 10 wt% based on 100 wt% of the first ceramic powder, the first dispersant can not be sufficiently evaporated in step S500 to be described later. In step S600, The heat treatment of the porous body may be hindered, and the strength of the produced porous ceramic support may be lowered.

Ball-miling or stirring may be performed to more uniformly mix the first ceramic powder, the first freezing medium, and the first dispersant. Specifically, the first slurry can be prepared by the ball milling. The ball milling finely crushes the first ceramic powder. In the step S300 described below, the wall of the first ceramic powder is made of a finer Density, so that the porous ceramic support can maintain its shape.

Next, in the step S200 of preparing the second slurry by mixing the second ceramic powder, the second freezing medium and the second dispersing agent, the second slurry must be prepared in a state of good fluidity, so that the freezing of the freezing medium It is preferable that the temperature is higher than the temperature.

The second ceramic powder is not limited as long as it is a ceramic having bone activity. Specifically, the second ceramic powder may be selected from the group consisting of hydroxyapatite (HA), alpha-tricalcium phosphate , α-TCP), β-tricalcium phosphate, tetracalcium phosphate (TTCP), amorphous calcium phosphate (ACP), monocalcium phosphate anhydrate , MCPA), dicalcium phosphate anhydrate (DCPD), octacalcium phosphate (OCP), monocalcium phosphate monohydrate (MCPM), dicalcium phosphate dehydrate (DCPD) ), Na ₂ O-CaO-SiO ₂ -P ₂ O ₅ , CaOSiO ₂ , P ₂ O ₅ -CaO-Na ₂ O and P ₂ O ₅ -CaO-K ₂ O, You can include it. , It specifies that not limited to this.

For example, the second ceramic powder may be hydroxyapatite.

The second freezing medium is not particularly limited as long as the energy required for removing the second freezing medium in step S500 of manufacturing a core-shell porous body described later is not excessive. Preferably, the second freezing medium may include at least one selected from the group consisting of water, Camphene, Camphor, naphthalene, and terpenoid, But is not limited thereto. In particular, the camphin can be used as a second freezing medium because the freezing temperature is 35 ° C to 45 ° C and can easily be evaporated and removed at room temperature to improve the energy efficiency in producing the porous ceramic substrate of the present invention .

The second dispersant serves to disperse the second ceramic powder in the second freezing medium and can be used without limitation as long as it can be easily dried and evaporated. Specifically, an oligomeric polyester may be used as the second dispersant.

Meanwhile, in step S200, the content ratio of the second ceramic powder and the second freezing medium may be adjusted in order to control mechanical properties such as porosity, pore size and compressive strength of the second frozen formed body to be manufactured later .

Since the porous ceramic support may exhibit a structure similar to that of a bone, it may be similar to a compact bone structure surrounding the cancellous bone. Accordingly, the porous body portion of the second freeze-molded body portion after the removal of the second freezing medium can be made into a structure having a small pore size, which is a compact bone structure. More specifically, the pore size of the porous article of the second freeze-molded article portion after the removal of the second freeze medium is adjusted within the range of 30 μm to 60 μm, and the porosity can be adjusted within the range of 20% to 30%. Accordingly, in order to produce the porous article having the above-described pore size and porosity, the weight of the second freezing medium may be 30 wt% to 100 wt%, more preferably 30 wt% % To 60% by weight. If the weight of the second freezing medium is less than 30% by weight of the second ceramic powder, the strength of the porous body is too weak to easily break down in the process of removing the second freezing medium after freeze-casting, which is not preferable . In addition, when the weight of the second freezing medium is more than 100% by weight based on 100% by weight of the second ceramic powder, three-dimensionally connected pores may not grow sufficiently, which is not preferable.

The weight of the second dispersant may be 0.1 wt% to 10 wt%, more preferably 0.5 wt% to 2 wt%, based on 100 wt% of the second ceramic powder. If the weight of the second dispersant is less than 0.1% by weight based on 100% by weight of the second ceramic powder, the ceramic powder may aggregate to form a second slurry having a uniform composition, which is not preferable. If the weight of the second dispersant is more than 10% by weight based on 100% by weight of the second ceramic powder, the second dispersant can not be sufficiently evaporated in step S500 to be described later. Further, in step S600 The heat treatment of the porous body may be hindered, and the strength of the produced porous ceramic support may be lowered.

Ball-miling or stirring may be performed to more uniformly mix the second ceramic powder, the second freezing medium and the second dispersant. Specifically, the second slurry can be prepared by the ball milling. The ball milling finely crushes the second ceramic powder. In the step (S400) described later, the wall of the second ceramic powder has a finer Density, so that the porous ceramic support can maintain its shape.

Next, the step (S300) of producing a first freeze-molded body by freezing the first slurry may include injecting the first slurry into the first mold, rotating and cooling the same.

The first slurry prepared in step S100 is injected into a first mold having a predetermined shape, rotated together with the first mold in the first mold, and cooled to produce the first freeze-molded body. At this time, the first mold into which the first slurry is injected may be manufactured into various shapes according to the field in which the porous ceramic support is used. As an example, the first template may be made of polyethylene or aluminum.

Specifically, in step S300, the first slurry is rotated in a predetermined speed range in the first mold to prevent precipitation of the first ceramic powder in the first slurry. By cooling the first slurry in this state, 1 < / RTI > This is based on the principle that the first ceramic powder to be precipitated in the first freeze medium is uniformly distributed to the first freeze medium by applying a constant driving force from the outside.

At this time, it is preferable that the rotational speed of the first mold is within the range of the first rotational speed to the second rotational speed. The first rotational speed means a rotational speed at which the first ceramic powder generates an external driving force equal to a force to be settled in the first freezing medium and the second rotational speed is a rotational speed at which the first ceramic powder Means the rotational speed at which an external driving force equal to the force is generated.

When the rotational speed of the first mold is slower than the first rotational speed, the force to deposit the first ceramic powder in the first freezing medium is larger than the external driving force caused by the rotation of the first mold, Layer separation occurs between the ceramic powders, which is undesirable. On the other hand, when the rotational speed of the first mold is faster than the specific second rotational speed, the external driving force generated due to the rotation of the first ceramic powder is greater than the force to be precipitated in the first freezing medium, so that the first ceramic powder, The freezing medium may cause layer separation due to the centrifugal effect, which is not preferable.

Meanwhile, in step S300, the porosity and the pore size of the porous ceramic support prepared through controlling the freezing temperature can be controlled. That is, the porosity and the pore size can be controlled by adjusting the interval of the coagulation phase of the first freezing medium by variously changing the freezing temperature during the rotation of the first slurry. Generally, the lower the freezing temperature is, the faster the nucleation rate becomes, and the interval of the condensation phase of the first freezing medium becomes narrow. Therefore, if the condensation phase of the first freezing medium is removed by the step S500 described later, The porosity and the pore size of the porous ceramic support are controlled by using a small size pore at a low freezing temperature and a large size pore at a relatively high freezing temperature.

However, it is preferable that the freezing temperature is adjusted within a range below the freezing temperature of the first freezing medium. For example, when the first freezing medium is a cam pin, the freezing temperature of the cam pin is 51 ° C to 52 ° C, The temperature at the time of freezing casting may be about 42 ° C.

Next, the step (S400) of manufacturing a core-shell freeze-molded body by manufacturing a second freeze-molded body by freezing the second slurry on the surface of the first freeze-molded body includes separating the first freeze- And then rotating and cooling the second slurry by injecting the second slurry into the empty space between the first freeze-molded body and the second mold, and then placing the second slurry in a second mold having a larger diameter than the first mold.

At this time, the second mold in which the first freeze-molded body is placed and the second slurry is injected may be manufactured in various shapes according to the field in which the porous ceramic substrate is used. As an example, the second mold may be manufactured using polyethylene or aluminum.

Specifically, in step S400, the second slurry is rotated in a predetermined speed range in the second mold to prevent precipitation of the second ceramic powder in the second slurry, and by cooling the second slurry in this state, 2 frozen shaped body can be produced. This is based on the principle that the second ceramic powder to be settled in the second freezing medium is forcedly distributed uniformly to the second freezing medium by externally applying a constant driving force.

At this time, the rotational speed of the second mold is preferably in the range of the third rotational speed to the fourth rotational speed. The third rotational speed means a rotational speed at which the second ceramic powder generates an external driving force equal to a force to be settled in the second freezing medium, and the fourth rotational speed is a rotational speed at which the second ceramic powder Means the rotational speed at which an external driving force equal to the force is generated.

When the rotational speed of the second mold is slower than the specified third rotational speed, the force to precipitate the second ceramic powder in the second freezing medium is larger than the external driving force caused by the rotation of the second mold, Layer separation occurs between the ceramic powders, which is undesirable. On the other hand, when the rotation speed of the second mold is faster than the specific fourth rotation speed, the external driving force generated by rotation of the second ceramic powder due to the rotation of the second ceramic powder is larger than the force to be precipitated in the second freezing medium, The freezing medium may cause layer separation due to the centrifugal effect, which is not preferable.

Meanwhile, in step S400, the porosity and the pore size of the porous ceramic support manufactured through the control of the freezing temperature can be controlled. That is, the porosity and pore size can be controlled by adjusting the interval of the coagulation phase of the second freezing medium by variously changing the freezing temperature during the rotation of the second slurry. Generally, the lower the freezing temperature is, the faster the nucleation rate becomes, and the interval of the condensation phase of the second freezing medium becomes narrower. Therefore, if the condensation phase of the second freezing medium is removed by the step S500 described later, The porosity and the pore size of the porous ceramic support are controlled by using a small size pore at a low freezing temperature and a large size pore at a relatively high freezing temperature.

However, it is preferable that the freezing temperature is controlled within a range below the freezing temperature of the second freezing medium, and since the pore size is smaller than that of the first freeze-molded body, the freezing temperature is lower than the freezing temperature Range is preferred. For example, if the first freezing medium is a cam pin, since the freezing temperature of the cam pin is 51 ° C to 52 ° C, the temperature during the freezing casting may be about 35 ° C.

When the second freeze-molded body is manufactured in the step S400, the first freeze-molded body manufactured in the above-described step S300 becomes the core-formed body, and the second freeze-molded body becomes the shell-formed body, A molded body can be manufactured.

In an embodiment of the present invention, after the step of manufacturing the core-shell freeze-molded article, the core-shell freeze-molded article may be subjected to the steps of: 1 freezing medium and granules of the second freezing medium. More specifically, the step of rotating the core-shell freeze-molded body while maintaining the core-shell freeze-molded body at a predetermined temperature range near the freezing temperature may include growing the granules of the first freezing medium and the second freezing medium.

The step of growing the granules of the first freezing medium and the second freezing medium may utilize a local remelting phenomenon of the frozen first freezing medium and the second freezing medium.

In the step of growing the granules of the first freezing medium and the second freezing medium for this process, the core-shell freeze-molded body is heated to a constant temperature of -20 캜 of the freezing temperature and the freezing temperature of the first freezing medium and the second freezing medium For a period of time to grow the coagulated phase. When the temperature is higher than the freezing temperature of the first freezing medium and the second freezing medium, it is not preferable that the first freezing medium and the second freezing medium are entirely melted and the core shell freezing compact is collapsed. In addition, when the temperature is lower than the freezing temperature of the first freezing medium and the second freezing medium, since the granulation does not occur or occurs very slowly, the time required for increasing the pore size is prolonged.

For example, when the camphin is used as the first freezing medium and the second freezing medium, the core shell freeze-molded body is maintained at a temperature of 25 캜 to 45 캜 for a predetermined time to grow a coagulated phase.

Next, the core-shell porous article is prepared by removing the first freezing medium and the second freezing medium from the core-shell freeze-molded article (S500).

In the above step (S500), the first freezing medium and the second freezing medium may be removed from the core-shell freeze-molded body by using any one of lyophilization, sublimation and dissolution. That is, by vacuum-treating the core-shell freeze-molded article in a frozen state and rapidly drying it, the first freezing medium and the second freezing medium are sublimated, or the first freezing medium and the second freezing medium in a frozen state are dissolved, Portions in which the first freezing medium and the second freezing medium exist in the shell freeze-molded body are formed as pores in the porous body.

Finally, the core-shell porous body is heat-treated (S600).

By heat treating the core-shell porous body, the core-shell porous body can be imparted with mechanical properties such as elasticity and stiffness similar to those of a living bone tissue.

At this time, the heat treatment temperature can be variously applied according to the first ceramic powder and the second ceramic powder to be used. As a concrete example, when the first ceramic powder or the second ceramic powder is hydroxyapatite, heat treatment may be performed at a temperature range of 1100 ° C to 1400 ° C. If the heat treatment temperature is less than 1100 ° C, the grains constituting the porous body may not be properly formed and it is difficult to obtain a desired strength. If the heat treatment temperature is higher than 1400 ° C, a part of the heat- There is a problem that it melts and flows down, which is undesirable.

The step S600 may be performed in a vacuum state in order to fundamentally block the problem that the porous body is oxidized by the non-reactant such as oxygen and the unnecessary impurities are mixed into the porous body.

At this time, there is no particular need to limit the degree of vacuum in the vacuum state, but more preferably 0.5 占^10-6 Torr to 1.0 占^10-6 Torr may be suitable. When the degree of vacuum is less than 0.5 x 10 < ^-6 > Torr, there is no effect of vacuum and the porous body can be oxidized. When the degree of vacuum is more than 1.0 x ^10-6 Torr, unnecessary manufacturing cost due to high vacuum can be increased I do not.

Hereinafter, a porous ceramic support manufactured by the method for manufacturing a porous ceramic support will be described.

The porous ceramic support may be manufactured in the form of a core shell by preparing an inner porous body by a freeze casting method, and then forming an outer porous body on the inner porous body by a freeze casting method. This is made similar to the core type of cancellous bone, which is a general bone structure, and the shell form of fine bone, in order to exhibit excellent mechanical properties and biological properties.

The pore size and the porosity of the porous ceramic support can be controlled by adjusting the content ratio of the ceramic powder and the freezing medium as raw materials for producing the porous ceramic support. The higher the concentration of the ceramic powder in the raw material, the smaller the pore size So that it is possible to display a compacted bone structure.

In addition to the content ratio of the ceramic powder and the freezing medium, there is a freezing temperature at the time of freezing casting. The lower the freezing temperature, the smaller the pore size and the smaller the pore size of the porous ceramic support. Structure can be expressed.

Hereinafter, a bone support including a porous ceramic support will be described.

The porous ceramic support may be manufactured in a similar manner to that of a core of a cancellous bone and a shell of a fine bone, which are general bone structures, and can be applied as a bone support.

Hereinafter, the porous ceramic support will be described.

The porous ceramic support may include a core-freeze-molded body having a pore size of 120 μm to 185 μm and a shell-freeze-molded body having a pore size of 30 μm to 60 μm formed on the surface of the core-freeze-molded body.

Because the porous ceramic support can be used for bone support applications, it should have a similar level of structure to bone and exhibit good mechanical and biological properties. Therefore, the porous ceramic support should exhibit a structure similar to that of the core of the cancellous bone and the shell of the fine bone, which are general bone structures.

The diameter of the core-freeze-molded body may not be limited depending on the intended use of the porous ceramic support, but may be in the range of 5 mm to 18 mm, which is desirable for use as a bone support. In order for the core-freeze-molded body to exhibit a structure similar to that of the core of the cancellous bone, it is preferable that the pore size is controlled to be several tens μm or more, more preferably 120 μm to 185 μm. Accordingly, if the core-freezing molded article has a pore size of 120 to 185 μm in a diameter of 5 mm to 18 mm, the porosity of the core-freeze-molded article may be 60% to 75%.

The diameter of the shell freeze-molded body may not be limited depending on the use of the porous ceramic support, but the diameter of the shell freeze-molded body must be longer than that of the core freeze-molded body. Thus, a preferred level for use as a bone support may be 10 mm to 36 mm. In order for the shell freeze-molded body to exhibit a structure similar to that of the compact bone, it is preferable that the pore size is controlled to a few tens of micrometers or less, more preferably 30 to 60 micrometers. Accordingly, if the shell freeze-molded article has a pore size of 120 μm to 185 μm in a diameter of 10 mm to 36 mm, the porosity of the shell freeze-molded article may be 20% to 30%.

Accordingly, the porosity of the porous ceramic support including the core-freeze-molded body and the shell-shaped-formed body may be in the range of 30% to 75%.

Hereinafter, Preparation Examples and Experimental Examples of the present invention will be described. However, these production examples and experimental examples are intended to explain the constitution and effect of the present invention more specifically, and the scope of the present invention is not limited thereto.

[Production Example 1]

Core shell  Form of bone support manufacturing

(Alfa Aesar, Ward Hill, Mass., USA) as a first ceramic powder, 11 g of a camphine (C ₁₀ H ₁₆ ) as a first freezing medium and ₁₀ g of an oligomer polyester (Hypermer KD- UniQema, Everburg, Belgium) was ball-milled at 60 ° C for 24 hours to prepare a first slurry. The first slurry was poured into a first polyethylene mold having a diameter of 10 mm and freeze-cast at 42 ° C for 24 hours to prepare a first freeze-molded body. The first freeze-molded body was detached from the first mold and fixed again to a second mold made of polyethylene having a diameter of 20 mm.

Next, 9.4 g of a camphin (C ₁₀ H ₁₆ ) as a second freezing medium and 5 g of an oligomer polyester (Hypermer KD) as a second dispersing agent were added as a second ceramic powder, 16 g of hydroxyapatite (Alfa Aesar, Ward Hill, MA, USA) -4, UniQema, Everburg, Belgium) was ball-milled at 60 ° C for 24 hours to prepare a second slurry. The second slurry was poured into an empty space in a second mold and freeze-cast for 24 hours at a temperature of 42 ° C to prepare a second freeze-molded body to prepare a core-shell freeze-molded body.

Thereafter, the core-shell freeze-molded body was separated from the second mold, and the core-shell porous article was prepared by maintaining the temperature at -34 ° C in a vacuum atmosphere of 1.0 × 10 ^-6 Torr in order to remove the first freezing medium and the second freezing medium . The core-shell porous body was heated to 1250 ° C at a heating rate of 7 ° C / min and maintained for 2 hours to prepare a bone support.

[Production Example 2]

Core shell  Form of bone support manufacturing

A bone support was prepared in the same manner as in Preparation Example 1, except that a first template having a diameter of 13.3 mm was used.

[Production Example 3]

Core shell  Form of bone support manufacturing

In Preparation Example 1, a bone support was prepared in the same manner except that a first template having a diameter of 16.7 mm was used.

[Comparative Example 1]

Manufacture of bone support

A bone support was prepared in the same manner as in Preparation Example 1, except that a first mold having a diameter of 20 mm was used to manufacture a second freeze-molded body to prepare a core-shell freeze-molded body.

[Comparative Example 2]

Preparation of bone support

TCP (Tissue Culture Plate) was prepared.

[Experimental Example 1]

Structural analysis of bone support

Production Example 1 was observed using Micro-CT to analyze the structure of the bone support.

3 is a Micro-CT image showing the porous ceramic support of Production Example 1. Fig. Referring to FIG. 3, it was confirmed that a defect-free bone scaffold was manufactured, and that a core shell structure exhibiting an outer dense bone structure and an internal cancellous bone structure was shown. Based on these results, it can be concluded that as the concentration of hydroxyapatite increases with the concentration of the slurry, the bone supporter is made into a compact bone structure, and the lower the concentration of hydroxyapatite is, the more the bone supporter is made of the cancellous bone structure.

[Experimental Example 2]

Analysis of Internal Structure of Bone Support

Production Example 1 was observed using a surface scanning microscope to analyze the structure of the bone support.

4 is an image of a surface scanning microscope according to the magnification shown inside the bone support of Production Example 1. Fig. Referring to FIG. 4, it was confirmed that shrinkage due to sintering occurred uniformly regardless of the vertical direction and the horizontal direction, and it was confirmed that there was no defect, and no shrinkage was observed at the boundary between the inside and the outside of the bone support. Based on these results, it can be judged that the sintering temperature of hydroxyapatite, which is a component of the bone support, is preferably 1250 ° C.

[Experimental Example 3]

The first freezing Shaped body  And the second freezing Of the shaped body  Analysis of Pore Structure of Bone Support by Area Ratio

In order to analyze the pore structure of the bone support according to the area ratio of the first and second freeze-molded bodies, the diameter of the second template was fixed and the diameter of the first template was changed to adjust the ratio of the inner diameter and outer diameter of the bone support The pore properties of the prepared bone support were analyzed.

5 is a micro-CT image showing a cross-section of a bone support according to the area ratio of the first freeze-molded body and the second freeze-molded body. The results of analyzing the porosity and pore size according to the area ratio of the first and second freeze-molded bodies are shown in Table 1 below.

[Table 1]

Referring to FIG. 5 and Table 1, it was confirmed that a bone support was produced without any structural defects regardless of the area ratio of the first and second freeze-molded bodies. Also, the internal porosity and the pore size are constant regardless of the area ratio of the first and second freeze-molded bodies, the external porosity and pore size are constant regardless of the area ratio of the first freeze-molded body and the second freeze-molded body, The overall porosity of the bony support increased as the internal diameter increased.

[Experimental Example 4]

The first freezing Shaped body  And the second freezing Of the shaped body  Analysis of compressive strength of bone support by area ratio

In order to analyze the compressive strength of the bone support according to the area ratio of the first freeze-molded body and the second freeze-molded body, the compressive strength of the bone support was analyzed using a compressive strength tester.

6 is a graph showing the compressive strength of the bone support according to the area ratio of the first freeze-molded body and the second freeze-molded body. Referring to FIG. 6, it was confirmed that the compressive strength was increased as the relative outer diameter ratio was increased, and it was confirmed that the compressive strength of the prepared bone support was within the compressive strength range of the internal cancellous bone.

[Experimental Example 5]

Analysis of cell attachment and proliferation of bone scaffolds

In order to analyze the degree of cell adhesion and proliferation of the bone supporter, the cells were attached to the bone supporter, and the bone supporter was observed using a light microscope, and the degree of cell proliferation after 3 and 5 days was analyzed.

7 is a light microscope image showing cells attached to the outside of the bone support of Comparative Example 2 (Fig. 7 (A)) and Production Example 1 (Fig. 7 (B) FIG. 2 is a graph showing the cell proliferation results of the bone support of FIG. Referring to FIGS. 7 to 8, it was confirmed that the cytoplasm of the bone support of the present invention spreads evenly irrespective of the inside and the outside, but in the case of TCP, the cytoplasm does not extend to the inside of the pore. In addition, when the cell proliferation time is 3 days, the bone support of the present invention has a cell viability about 1.3 times higher than that of TCP, and when the cell proliferation time is extended to 5 days, it becomes about 1.9 times higher than that of TCP, Of the total population.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims (23)

Preparing a first slurry by mixing a first ceramic powder, a first freezing medium, and a first dispersant;
Preparing a second slurry by mixing a second ceramic powder, a second freezing medium, and a second dispersant;
Freezing the first slurry to produce a first freeze-molded body;
Freezing the second slurry on the surface of the first freeze-molded body to produce a second freeze-molded body to produce a core-shell freeze-molded body;
Removing the first freezing medium and the second freezing medium from the core-shell freeze-molded body to manufacture a core-shell porous body; And
And heat treating the core-shell porous body,
Wherein the pore size of the first freeze-molded article is larger than the pore size of the second freeze-molded article,
Wherein the pore size of the first freeze-molded body is controlled by the content ratio of the first ceramic powder and the first freeze medium, and the pore size of the second freeze-molded body is controlled by the content ratio of the second ceramic powder and the second freeze medium .
Wherein the weight of the first freezing medium is 100 wt% to 500 wt% based on 100 wt% of the first ceramic powder, the pore size of the core portion of the core-shell porous body is adjusted within a range of 120 μm to 185 μm , And the porosity is controlled within a range of 60% to 75%
And the second freezing medium is 30 to 100% by weight based on 100% by weight of the second ceramic powder. The pore size of the shell portion of the core-shell porous body is controlled within a range of 30 to 60 占 퐉. And the porosity is controlled within a range of 20% to 30%.
delete The method according to claim 1,
The first ceramic powder or the second ceramic powder may be at least one selected from the group consisting of hydroxyapatite (HA), alpha-tricalcium phosphate (alpha-TCP), beta-tricalcium phosphate TCP, tetracalcium phosphate (TTCP), amorphous calcium phosphate (ACP), monocalcium phosphate anhydrate (MCPA), dicalcium phosphate anhydrate (DCPD), octacalcium phosphate octacalcium phosphate (OCP), monocalcium phosphate monohydrate (MCPM), dicalcium phosphate dehydrate (DCPD), Na ₂ O-CaO-SiO ₂ -p ₂ O ₅ , CaOSiO ₂ , P ₂ O ₅ -CaO-Na ₂ O, and P ₂ O ₅ -CaO-K ₂ O. _{2. The} method for producing a porous ceramic support according to claim 1,
The method according to claim 1,
Wherein the first freezing medium or the second freezing medium includes at least one selected from the group consisting of water, Camphene, Camphor, naphthalene and terpenoid-based materials ≪ / RTI >
The method according to claim 1,
Wherein the first dispersant or the second dispersant comprises an oligomeric polyester. ≪ RTI ID = 0.0 > 11. < / RTI >
delete The method according to claim 1,
Wherein the weight of the first dispersant is 0.1 wt.% To 10 wt.% Relative to 100 wt.% Of the first ceramic powder.
delete The method according to claim 1,
Wherein the weight of the second dispersant is 0.1 wt.% To 10 wt.% Relative to 100 wt.% Of the second ceramic powder.
The method according to claim 1,
Wherein the step of preparing the first freeze-molded body is performed at a temperature below the freezing temperature of the first freezing medium.
The method according to claim 1,
Wherein the first slurry is injected into the first mold and rotated and cooled in the step of producing the first freeze-molded body.
The method according to claim 1,
Wherein the step of preparing the core-shell freeze-molded article is performed at a temperature below the freezing temperature of the second freezing medium.
The method according to claim 1,
Wherein the second slurry is injected into the second mold and is rotated and cooled in the step of producing the core shell freeze-molded body.
The method according to claim 1,
Wherein the first slurry is injected into a first mold, the second slurry is injected into a second mold to be rotated and cooled,
Wherein the size of the first mold is smaller than the size of the second mold.
The method according to claim 1,
Further comprising the step of growing the granules of the first freezing medium and the second freezing medium between the step of producing the core shell freeze-molded body and the step of producing the core-shell porous article, Way.
The method according to claim 1,
Wherein the step of heat-treating the core-shell porous body is performed in a vacuum state at a temperature range of 1100 ° C to 1400 ° C.
A porous ceramic support produced by the method of claim 1.
17. A bone support comprising the porous ceramic support of claim 17.
delete delete delete delete delete

Images