KR20180062132A - Composition for three-dimensional ceramic scaffold having dual-pore - Google Patents

Abstract

The present invention relates to a bioceramics composition comprising i) 33.7 to 43.7% by weight of bio-ceramic particles; ii) 31.2 to 41.2% by weight of a liquid dispersant; iii) 2.3 to 7.3% by weight of a viscous agent; iv) 9.5 to 19.5% by weight of flocculant; And v) less than 11% by weight of sodium alginate.
The composition for a three-dimensional ceramic artificial support having a double void according to the present invention comprises sodium alginate capable of forming a large amount of microvoids on the surface of a scaffold and bioceramics having the same or similar structure as the main inorganic constituent of the bones of the human body The present invention can provide a suitable environment for promoting adhesion, proliferation and differentiation of cells by preparing a slurry with the above-mentioned composition, feeding the prepared slurry to the polymer mold, and then performing heat treatment and firing In addition, it is possible to produce a three-dimensional ceramic scaffold with double voids having excellent mechanical properties.

Description

TECHNICAL FIELD [0001] The present invention relates to a three-dimensional ceramic scaffold having a dual-pore structure,

The present invention relates to a composition capable of producing a three-dimensional ceramic scaffold with double voids.

In the field of bone tissue engineering, biomedical scientists have developed a three-dimensional bio-scaffold that can be inserted into defects to restore lost bone tissue. . The scaffold may serve as a support for providing a suitable environment in vivo for adhesion, proliferation, and differentiation of cells necessary for reconstitution of a living body skeleton and a tissue.

Currently known materials for the production of scaffolds are broadly classified into polymers, metals, ceramics and composites. Among them, the ceramic material is most related to the bones of the human body, such as a goal frame or bone cement.

Particularly, among the ceramic materials, biphasic calcium phosphate (BCP) belonging to the oxide series is a bioceramics synthesized with beta-tricalcium phosphate (TCP) and hydroxyapatite (HA) -TCP, and low solubility of HA, as well as being most chemically similar to the constituents of bone and tooth minerals, it is widely used as a material suitable for bone tissue regeneration , The BCP has a disadvantage of low mechanical strength and low resistance.

Recently, BCP has been mixed with silica or the like to be used as a material for preparing a scaffold. The silica has been widely used as a raw material for improving the strength and toughness of ceramics, Can be improved not only in adhesion and proliferation but also in biocompatibility and osteoconductivity. Thus, it is widely used for bone tissue regeneration.

Conventionally, studies for manufacturing a scaffold by combining a 3D printing method and a mold method have been progressing actively, and a technical description about a method for manufacturing a three-dimensional scaffold using extrusion lamination molding technology or a stereolithography technique Lt; / RTI >

However, since the synthetic polymer used for producing the scaffold is different from that of the actual bone tissue, the cell adhesion, proliferation and differentiation are not easily induced, and it is difficult to introduce the synthetic polymer directly into the living body. There is a need for research on how to supplement this.

 Young-Joon Seol, Jong Young Kim, Eui Kyun Park, Shin-Yoon Kim and Dong-Woo Cho, "Fabrication of a hydroxyapatite scaffold for bone tissue regeneration using microstereolithography and molding technology", Microelectronic Engineering, 86, pp. 1443-1446, 2009.  Sabree I., Gough, J. E. and Derby, B., "Mechanical properties of porous ceramic scaffolds: Influence of internal dimensions," Ceramic International, Vol. 41, pp. 8425-8432, 2015.  Mohanty, S., Sanger, K., Heiskanen, A., Trifol, J., Szabo, P., Dufva, M., Emneus, J. and Wolff, A., "Fabrication of scalable tissue engineering scaffolds with dual- pore microarchitecture by combining 3D printing and particle leaching, "Materials Science and Engineering C, Vol. 61, pp. 180 ~ 189, 2016.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and it is an object of the present invention to provide a biocompatible porous ceramic material which comprises bioceramic ceramic particles substantially identical or very similar to actual bone tissue and sodium alginate capable of forming a large amount of microvoids The present invention is directed to a composition for a three-dimensional ceramic artificial support capable of providing a suitable environment for promoting adhesion, proliferation and differentiation of cells, and capable of forming a scaffold having excellent mechanical properties.

In order to accomplish the above-mentioned technical object, the present invention provides a bioceramics composition comprising i) 33.7 to 43.7% by weight of bio-ceramic particles; ii) 31.2 to 41.2% by weight of a liquid dispersant; iii) 2.3 to 7.3% by weight of a viscous agent; iv) 9.5 to 19.5% by weight of flocculant; And v) less than 11% by weight of sodium alginate.

In addition, the bioceramics particle may be at least one organic ceramic material selected from the group consisting of calcium phosphate ceramics, hydroxyapatite, and anhydrous calcium phosphate, and one or more kinds selected from the group consisting of silica, zirconia, zinc peroxide and magnesium peroxide Or more of the filler.

The liquid dispersant may be selected from the group consisting of ammonium polymethacrylate, ethanol, dimethylformamide (DMF), dimethylacetamide, and tetrahydrofuran And at least one of them.

The viscous agent may be at least one selected from the group consisting of hydroxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, amorphous cellulose, gelatin, casein, dextran, And at least one selected from the group consisting of gum arabic gum, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, poloxamer and eudragit.

The coagulant may be at least one selected from the group consisting of polyethylenimine, chitosan and chitosan derivatives.

The present invention also provides a method for producing a three-dimensional ceramic scaffold with dual voids using the composition described above, comprising the steps of: (a) preparing a composition comprising bioceramic ceramic particles, a liquid dispersant, a viscous agent, a coagulant and sodium alginate Preparing a slurry; (b) supplying the slurry to a polymer mold having a three-dimensional structure to produce a mold-slurry structure; (c) heat treating the mold-slurry structure to produce a slurry structure; And (d) sintering the slurry structure. The present invention also provides a method of manufacturing a two-pore porous three-dimensional ceramic scaffold.

The polymer mold is characterized by being formed by laminating biocompatible polymers by a fused deposition modeling (FDM) method.

The composition for a three-dimensional ceramic artificial support having a double void according to the present invention comprises sodium alginate capable of forming a large amount of microvoids on the surface of a scaffold and bioceramics having the same or similar structure as the main inorganic constituent of the bones of the human body The present invention can provide a suitable environment for promoting adhesion, proliferation and differentiation of cells by preparing a slurry with the above-mentioned composition, feeding the prepared slurry to the polymer mold, and then performing heat treatment and firing In addition, it is possible to produce a three-dimensional ceramic scaffold with double voids having excellent mechanical properties.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a process drawing showing a method for producing a scaffold of the embodiment. Fig.
2 is a SEM image of a mold manufactured by the method according to the embodiment.
3 is an SEM image of a three-dimensional ceramic scaffold prepared by the method according to the embodiment and having double voids.
4 is an SEM image of a magnified photograph of the surface of the scaffold of (a) Comparative Example 1, (b) Example, (c) Comparative Example 2 and (d)
FIG. 5 shows the results of analysis of the stress-strain curves (a), (b), and (c) compressive elastic modulus of the scaffold of Examples and Comparative Examples 1 to 3.

Hereinafter, the present invention will be described in detail.

The present invention relates to a bioceramics composition comprising i) 33.7 to 43.7% by weight of bio-ceramic particles; ii) 31.2 to 41.2% by weight of a liquid dispersant; iii) 2.3 to 7.3% by weight of a viscous agent; iv) 9.5 to 19.5% by weight of flocculant; And v) less than 11% by weight of sodium alginate.

The composition preferably has biocompatibility and is introduced in vivo, and preferably contains a stable biocompatible material.

The bioceramics particles serve to impart the mechanical strength of the scaffold to be produced, and materials having the same or similar structure as the main inorganic material constituting the bones of the human body can be used.

The bioceramics particles may include an organic ceramic material including calcium phosphate ceramics, hydroxyapatite, anhydrous calcium phosphate, or a mixture thereof, and an organic ceramic material including silica, zirconia, zinc peroxide, magnesium peroxide, It is possible to form a scaffold having excellent chemical and mechanical properties.

Preferably, the composition may comprise bioceramics particles comprising anhydrous calcium phosphate and silica, and the bioceramics particles may be prepared by using fine particles having an average particle size of 50 to 200 nm, .

The liquid dispersant contained in the composition plays a role of uniformly dispersing and stabilizing the bio-ceramic particles, and can be prepared by dispersing and stabilizing the bio-ceramic particles in a solvent such as ammonium polymethacrylate, ethanol, dimethylformamide (DMF), dimethylacetamide dimethylacetamide, tetrahydrofuran, and the like, but the present invention is not limited thereto. Preferably, ammonium polymethacrylate having excellent biocompatibility can be used.

The viscous agent contained in the composition serves to increase the tackiness and viscosity between the bioceramics particles and may be selected from the group consisting of hydroxymethylcellulose, gelatin, casein, dextran, gum arabic, tragacanth gum, polyethylene glycol, carboxymethylcellulose, Hydroxypropylmethylcellulose, amorphous cellulose, polyvinyl alcohol, polyvinylpyrrolidone, poloxamer, eudragit, or a mixture thereof may be used as a representative example of the hydrophilic polymer such as hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, For example. Preferably, hydroxypropyl methylcellulose having excellent biocompatibility with the viscous agent can be used, and is not limited to the form of liquid, powder or the like.

The coagulant contained in the composition serves to coagulate the bio-ceramic particles, and examples thereof include polyethylenimine, chitosan, chitosan derivatives, or a mixture thereof. Preferably, polyethyleneimine may be used as the coagulant, and is not limited to the form of liquid or powder.

The sodium alginate contained in the composition can serve as a thickening stabilizer for increasing the mechanical strength of a scaffold prepared by imparting tackiness and viscosity, and can also serve as a thickening stabilizer for forming a double void in the scaffold by sintering It plays a role. The sodium alginate is not limited to the form of a liquid phase, powder or the like.

On the other hand, the composition can control physical properties by mixing the bio-ceramic particles, the dispersant, the viscous agent, the coagulant and the void-forming agent at various mixing ratios. In particular, the addition of sodium alginate to the composition not only improves the mechanical strength of the scaffold, but also allows the formation of double voids in the scaffold.

To this end, the composition comprises 33.7 to 43.7% by weight of bioceramics particles, 31.2 to 41.2% by weight of a dispersant, 2.3 to 7.3% by weight of a viscous agent, 9.5 to 19.5% by weight of a flocculating agent and 0 to 11% by weight of sodium alginate The scaffold formed by using such a composition has excellent properties such as mechanical strength and compressive elastic modulus and can be stably introduced into a living body and used.

When the composition contains less than 33.7% by weight of bioceramics, the strength of the scaffold is weak and it is difficult to maintain its shape during the regeneration period of the tissue. When the composition contains more than 43.7% by weight, Is reduced.

When the composition contains less than 31.2% by weight of the dispersing agent, it is difficult to stabilize and uniformly disperse the bioceramics particles. If the composition contains more than 41.2% by weight of the dispersion, the mechanical strength of the scaffold becomes poor.

When the composition contains less than 2.3% by weight of the viscous agent, it is difficult to maintain the viscosity. When the composition contains more than 7.3% by weight of the viscous agent, the bioceramics particles aggregate and are difficult to uniformly disperse.

When the amount of the coagulant is less than 9.5 wt%, the cohesive force of the composition deteriorates, and the mechanical strength of the scaffold is deteriorated. When the coagulant is contained in an amount exceeding 19.5 wt%, the coagulant is hardly coagulated and uniformly dispersed.

When sodium alginate is not contained in the composition, there is a problem that a large amount of double voids are not formed in the scaffold. When the composition contains more than 11% by weight of the scaffold, the mechanical strength of the scaffold is lowered. By weight and 10% by weight, so that excellent mechanical properties can be achieved.

The composition as described above contains bioceramic ceramic particles which are the same as or very similar to the actual bone tissue and sodium alginate capable of forming a large amount of microvoids on the surface of the scaffold, and are suitable for promoting cell adhesion, proliferation and differentiation Environment can be provided, and a scaffold having excellent mechanical properties can be formed.

The present invention also provides a method for producing a three-dimensional ceramic scaffold with dual voids using the above-described composition, comprising the steps of: (a) preparing a slurry comprising bioceramic ceramic particles, a liquid dispersant, a viscous agent, a coagulant and sodium alginate Producing; (b) supplying the slurry to a polymer mold having a three-dimensional structure to produce a mold-slurry structure; (c) heat treating the mold-slurry structure to produce a slurry structure; And (d) sintering the slurry structure. The present invention also provides a method of manufacturing a two-pore porous three-dimensional ceramic scaffold.

The step (a) is a step of preparing a slurry containing bioceramics particles, a liquid dispersant, a viscous agent, a flocculant, and sodium alginate.

Said composition comprising 33.7 to 43.7% by weight of bioceramics particles, 31.2 to 41.2% by weight of a dispersant, 2.3 to 7.3% by weight of a viscous agent, 9.5 to 19.5% by weight of flocculating agent and 0 to 11% by weight of sodium alginate , The mechanical strength and the compressive elastic modulus of the scaffold formed in the step to be described later are excellent and can be stably introduced into the living body and used.

Also, the slurry can be prepared through a heat treatment process in which the composition is heated at a temperature of 50 to 70 ° C for 20 to 40 minutes, thereby removing gas components contained in the slurry, increasing the cohesive force, And the bioceramics particles are homogeneously mixed to form a scaffold having a uniform density.

In addition, since the slurry prepared in this step can be supplied to the polymer mold to be molded and removed to remove the polymer mold to form a scaffold, it is possible to mix the bioceramics particles, dispersant, viscous agent, flocculant, The mixing ratio can be adjusted to control the physical properties. Particularly, the composition includes not only a mechanical strength but also a pore-forming formed scaffold.

The step (b) is a step of supplying the slurry to a polymer mold having a three-dimensional structure to prepare a mold-slurry structure. The slurry may be filled in the polymer mold to mold the slurry into a specific shape by a mold. So that the structure can be formed.

The polymer mold is removed by heat treatment or calcination, and a biocompatible polymer capable of being completely decomposed in vivo in a desired time without inducing blood coagulation or inflammatory reaction after being introduced into the living body even if a trace amount remains in the scaffold. Anything made of materials can be used without restriction.

The biocompatible polymer may be selected from the group consisting of polycaprolactone (PCL), poly (lactic acid), PLA, polyglycolic acid, PGA, poly (lactic-co) polyglycolic acid (PLGA), polyurethane (PU), or a mixture thereof. A polymer mold made of polycaprolactone (PCL) may be used as the biocompatible polymer.

In particular, the polymer mold may be a polymer mold of precise shape formed by laminating a biocompatible polymer by a fused deposition modeling (FDM) method.

The above-described fused deposition modeling (FDM) is a rapid prototyping technique and can be controlled with a precision of several tens of microns, so that a precise mold can be manufactured in a suitable size and shape for in vivo introduction.

In the three-dimensional printing using the thermal dissolution laminating method, a biocompatible polymer-containing mixture is supplied to a 3D printing apparatus, the mixture is heated and melted in a dispenser, and the melted mixture is discharged through a nozzle using air pressure When the mixture is injected in the form of a strand by the three-dimensional movement of the nozzle, the injected fibers are entangled with each other and floated in three dimensions to form the polymer mold of the mesh structure. At this time, the nozzle having a diameter of 100 to 500 탆 may be used. The fibers may be sprayed with a length of 50 to 500 탆 in a square grid having a mesh structure, It is preferable to use a polymer mold.

The step (c) may include a step of heat-treating the mold-slurry structure to produce a slurry structure. The mold-slurry structure may be heat-treated to remove the polymer mold and form a slurry structure.

For this purpose, this step may be performed by heat treatment at a temperature of 90 to 110 ° C. for 1 to 3 hours to remove the polymer mold from the mold-slurry structure to form a slurry structure including the bioceramics particles.

The step (d) is a step of sintering the slurry structure, wherein the slurry structure is sintered to improve the binding density of the bio-ceramic particles contained in the slurry structure to form a scaffold, Sodium alginate causes a large amount of micro- or nanometer-sized microvoids on the surface of the scaffold.

Therefore, the scaffold prepared through this step is formed by a polymer mold, and a double structure including micropores formed on the surface of the scaffold is formed by sintering the slurry structure containing the pore formed by the scaffold itself and the sodium alginate It is possible to form the artificial scaffold.

In this step, a scaffold can be manufactured by sintering at a temperature of 1,000 to 1,400 ° C for 1 to 3 hours. If the sintering temperature is less than 1,000 ° C, the shrinkage rate is low, the binding density and mechanical strength of the bioceramics particles are lowered, When the temperature exceeds 1,400 DEG C, there is a problem that it is difficult to obtain an optimal three-dimensional scaffold because the phase and crystal structure of the bioceramics particles are changed.

As described above, the composition for a three-dimensional ceramic artificial support having double voids according to the present invention comprises sodium alginate capable of forming a large amount of microvoids on the surface of a scaffold and the same or similar structure as main inorganic elements constituting the bones of the human body And the slurry is supplied to the polymer mold, and then the slurry is supplied to the polymer mold, followed by heat treatment and firing. In order to promote adhesion, proliferation and differentiation of the cells, It is possible to produce a three-dimensional ceramic scaffold having double voids with excellent mechanical properties.

Further, the present invention provides a scaffold having the double void structure formed of the above composition.

The scaffold includes bioceramic particles having the same or similar structure as the main inorganic material constituting the bones of the human body, so that it is not only biocompatible, but also has excellent mechanical strength and provides a suitable environment for cell attachment, proliferation and differentiation A double void is formed so that it can be utilized as a biomedical application.

Particularly, when the surface of the scaffold is coated with a protein promoting bone formation such as BMP protein or NELL protein, the protein can be effectively immobilized on the double cavity formed in the scaffold, thereby achieving an excellent bone formation effect .

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

The embodiments presented are only a concrete example of the present invention and are not intended to limit the scope of the present invention.

<Examples>

A scaffold was prepared using the composition in the order shown in Fig.

(1) Production of slurry

(Davan® C, RT Vanderbilt, USA), 0.1 g of hydroxymethylcellulose (Sigm-Aldrich, USA), 0.75 mL of polymethacrylate (RT Vanderbilt, USA) , 0.3 mL of polyethyleneimine (Sigm-Aldrich, USA) and 10 wt% sodium alginate powder were added and uniformly mixed with a spatula to prepare a composition. The prepared composition was heat-treated for 10 minutes in an oven (oven, OF-12, JEIO TECH, Korea) to remove the gas contained in the mixture and increase the cohesive force to prepare a slurry. The prepared slurry was evenly mixed and heat-treated in an oven under the same conditions to further increase the cohesion, and a slurry for the preparation of a scaffold was prepared.

(2) Production of PCL mold

Polycaprolactone molds (PCL molds) with a three - dimensional structure were prepared using a three - dimensional printing method.

First, a double-faced tape was attached to a working flat plate for polymer lamination, and a polymer was laminated on the upper surface of the double-faced tape to prepare a PCL mold. In order to prevent the ceramic slurry from leaking out of the mold when the ceramic slurry was filled, the polymer layer was laminated at intervals of 0.75 mm in the first layer and at intervals of 1.5 mm from the second layer, and the outer wall was completely clogged And laminated to prepare a PCL mold. For this, a 10 cc steel syringe and a 500 탆 precision nozzle were filled with PCL polymer particles, heated to 100 캜 using a heater, injected at a feed rate of 200 mm / min and a 500 탆 line width using an air pressure of 650 kPa on average Through this, a PCL mold having a pore size of 1 mm and a size of 8.2 × 8.2 × 3.5 mm was produced.

(3) Preparation of mold-slurry structure

The slurry for the preparation of the scaffold and the PCL mold were mixed at a weight ratio of 1: 1, the slurry for preparing the scaffold was densely packed in the PCL mold, and dried naturally for one day to prepare a mold-slurry structure including the mold and the slurry.

In order to remove the PCL mold, the mold-slurry structure was heat-treated in an oven at 100 ° C for 2 hours to remove the PCL molds on the bottom and outer wall surfaces and to form a three-dimensional, more rigid mold- .

(4) Production of three-dimensional ceramic scaffold

The slurry structure was naturally dried for 2 hours and then sintered in an electric furnace (MF-12H, JEIO TECH, Korea) at a temperature of 1100 ° C for 2 hours to prepare a three-dimensional ceramic scaffold.

&Lt; Comparative Example 1 &

A mold-slurry structure was prepared in the same manner as in Example except that a slurry was prepared from a composition not containing sodium alginate, and a scaffold was prepared using the mold-slurry structure.

&Lt; Comparative Example 2 &

A slurry composition was prepared in the same manner as in Example 1 except that a slurry was prepared from a composition containing 20% by weight of sodium alginate powder, and a scaffold was prepared using the same.

&Lt; Comparative Example 3 &

A slurry composition was prepared in the same manner as in Example 1 except that a slurry was prepared from a composition containing 30% by weight of sodium alginate powder, and a scaffold was prepared using the same.

EXPERIMENTAL EXAMPLE 1 Analysis of morphological characteristics of molds, structures and scaffolds

(1) PCL mold

In order to confirm the shape of the produced PCL mold, a PCL mold was photographed using a scanning electron microscope (SEM), and the result is shown in FIG.

As shown in Fig. 2 (a), it can be confirmed that the produced PCL mold has a three-dimensional solid shape, and as shown in Fig. 2 (b), the PCL mold has a line- .

(2) Mold-slurry structures

As a result, it was confirmed that the mold-slurry structure had a size of 5.7 × 5.7 × 3.0 mm, a line width of 1 mm, and a pore size of 500 μm.

(3)

In order to analyze the morphological characteristics of the manufactured three-dimensional ceramic scaffold, a three-dimensional ceramic scaffold prepared by the method according to the embodiment using a scanning electron microscope was photographed. The results are shown in FIG.

As shown in FIG. 3, it was confirmed that the manufactured scaffold had a three-dimensional shape, and that double voids were formed. The scaffold showed very rough surface characteristics, and it was considered that the scaffold would be very advantageous for adhesion, proliferation and differentiation of cells .

It was also confirmed that the prepared scaffolds had an average size of 5.8 × 5.8 × 2.8 mm, a line width of 1400 μm, and a pore size of 360 μm. When the sintering caused shrinkage, the mold- And the size was decreased compared to that of.

(4) Calculation of apparent density and porosity of scaffold

In order to analyze the pore characteristics formed on the surface of the scaffold formed by sodium alginate, the apparent density of the scaffold according to Examples and Comparative Examples 1 to 3 was calculated and the apparent density g / cm &lt; ³ &gt;). The results are shown in Table 1 below. In addition, a precise balance (Pioneer PAG214, Ohaus Corp., USA) was used to measure the mass (where S _m is the mass and S _v is the volume).

[Equation 1]

In order to analyze the pore characteristics formed on the surface of the scaffold formed by sodium alginate, the porosity of the scaffold according to Examples and Comparative Examples 1 to 3 was calculated, and the porosity was calculated using the following formula (2) The results are shown in Table 1 below (where V is the total volume of the scaffold, M is the mass, and p is the density).

&Quot; (2) &quot;

As shown in Table 1, it was confirmed that the addition amount of sodium alginate affects the morphology of the scaffold. In Comparative Example 1 in which sodium alginate was not added, shrinkage progressed by 9.31%. However, as the addition amount of sodium alginate increased, the binding force between the bioceramic microparticles became weaker and the shrinkage was not good.

As a result of measuring the porosity of the prepared scaffold, it was confirmed that porosity of the scaffold increased as the amount of sodium alginate (0 wt%, 10 wt%, 20 wt%, and 30 wt%) was increased (See FIG. 4).

&Lt; Experimental Example 3 > Evaluation of mechanical properties of a scaffold

In order to evaluate the mechanical properties of the manufactured scaffold, the compressive strength and compressive elastic modulus of the scaffold prepared by the method according to Examples and Comparative Examples 1 to 3 were measured, and the results are shown in Fig. The compressive strength of the scaffold was measured using a compression tester (JSV-H1000, Japan) at a feed rate of 1 mm / min and the load-displacement curve during the compression test was monitored by computer. The elastic modulus (E) of the scaffold was calculated from the compression test diagram and the mean value was calculated using four identical scaffolds.

5 shows the results of analysis of the stress-strain curves (a), (b) compressive strength and (c) compressive elastic modulus of the scaffolds according to Examples and Comparative Examples 1 to 3.

As shown in FIG. 5, it was confirmed that the shrinkage percentage of the scaffold prepared by the method according to the embodiment was the best, and the compressive strength and the elastic modulus were related to the shrinkage ratio. Sodium alginate was determined to have retained the particles well until the sintering was completed after the slurry was prepared, but it was confirmed that the alginate swells during the sintering due to the swelling property when the content is increased.

As compared with Comparative Example 1 in which sodium alginate was not added, the mechanical properties of the scaffold according to the Examples were improved. Sodium alginate not only increased the stickiness and viscosity of the slurry but also increased the binding force of the ceramic scaffold And it can be confirmed that a large amount of double pores can be formed.

As a result, it was confirmed that the composition according to the present invention can form a double pore, and can produce a scaffold having excellent mechanical properties and morphological characteristics. It is also confirmed that the conventional scaffold has a compressive strength Compared with the range (1 to 10 MPa), the scaffold prepared from the composition according to the present invention had a compressive strength of 8.90 ± 0.58, showing not only excellent mechanical properties but also rough surface characteristics, and a large amount of micropores It was considered that the double pore structure could provide a favorable environment for cell adhesion, proliferation and differentiation.

Claims (7)

i) 33.7 to 43.7% by weight of bio-ceramic particles; ii) 31.2 to 41.2% by weight of a liquid dispersant; iii) 2.3 to 7.3% by weight of a viscous agent; iv) 9.5 to 19.5% by weight of flocculant; And v) less than 11% by weight sodium alginate. The method according to claim 1,
Wherein the bioceramics particles comprise at least one organic ceramic material selected from the group consisting of calcium phosphate ceramics, hydroxyapatite and anhydrous calcium phosphate and at least one filler selected from the group consisting of silica, zirconia, zinc peroxide and magnesium peroxide The composition for a three-dimensional ceramic artificial support according to claim 1, The method according to claim 1,
The liquid dispersant may be at least one selected from the group consisting of ammonium polymethacrylate, ethanol, dimethylformamide (DMF), dimethylacetamide, and tetrahydrofuran By weight based on the total weight of the composition. The method according to claim 1,
The viscosifying agent may be at least one selected from the group consisting of hydroxymethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, amorphous cellulose, gelatin, casein, dextran, Wherein the composition comprises at least one selected from the group consisting of rubber, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, poloxamer, and eudragit. The method according to claim 1,
Wherein the coagulant comprises at least one member selected from the group consisting of polyethylenimine, chitosan and chitosan derivatives. A method for producing a scaffold using the composition according to any one of claims 1 to 5,
(a) preparing a slurry with a composition comprising bioceramic ceramic particles, a liquid dispersant, a viscous agent, a flocculant, and sodium alginate;
(b) supplying the slurry to a polymer mold having a three-dimensional structure to produce a mold-slurry structure;
(c) heat treating the mold-slurry structure to produce a slurry structure; And
(d) sintering the slurry structure. &lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt; The method according to claim 6,
Wherein the polymer mold is formed by laminating a biocompatible polymer by a fused deposition modeling (FDM) method.

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