KR101712555B1 - Porous scaffold compositions for tissue engineering and process for preparing thereof - Google Patents

Abstract

The present invention provides a tissue-engineering porous calcium phosphate scaffold composition, and a method for producing a porous calcium phosphate scaffold composition by using a physical foaming scheme. To this end, a porous scaffold composition according to the present invention comprises: 45-58 wt% of calcium phosphate powder; 40-50 wt% of one or more aqueous monomers selected from N-hydroxymethyl acrylamide and N,N-methylenebisacrylamide; 0.6-1.5 wt% of polyoxyethyelene sorbitan monooleate; 0.8-2 wt% of one or more anion surfactants selected from alkyl sulfate and alkyl ether sulfate; and 0.2-0.5 wt% of a dispersing agent selected from polycarboxylic acid ammonium salt and polycarboxylic acid sodium salt.

Description

TECHNICAL FIELD [0001] The present invention relates to a porous scaffold composition for tissue engineering,

The present invention relates to a porous scaffold composition for tissue engineering and a method for preparing the same, and more particularly, to a composition for a porous calcium phosphate scaffold used in dental and orthopedic fields and a method for producing a porous calcium phosphate scaffold using the same .

Today, there are many studies for bone substitution and bone regeneration due to the entry into the aging society and the increase of bone disease patients. In particular, implant technology that directly replaces teeth or femur using non-absorbable biomaterials such as titanium and metal such as ceramics has already been used extensively in clinical practice as a replacement for damaged tissue.

However, since non-absorbable biomaterials have difficulties in directly replacing the local bone defect and need to be removed through secondary surgery after recovery as needed, Researches on artificial bone formation and procedures using biodegradable scaffolds, which are degraded by bone grafting, have been actively conducted.

Biological tissues are maintained in shape and function by the interaction of various cells with extracellular substances, and various life phenomena are controlled. Among the extracellular substances, organic solid substances called extracellular matrix (ECM), which is composed mainly of organic polymers such as proteins and polysaccharides, exist as crosslinked gel or porous networks in biological tissues. It acts as a structural support for the tissue and as a cell adhesion promoter. When cells attach to ECM, intracellular signal transduction is activated and basic cellular functions such as cell morphology, differentiation, proliferation, and cell death are controlled.

Scaffolds are artificially made ECMs for tissue establishment and cell function control, and are designed with biocompatibility, biodegradability, porosity, moisture content, delivery, and cell adhesion.

In particular, porosity should maintain sufficient pore size and number in the scaffold to maintain cell activity through nutrients and by-product in and out communication.

Recently, much attention has been focused on gel-type scaffolds and porous scaffolds similar to bio-ECM in terms of structure. Gel scaffolds can be easily injected into unformed damaged tissues by direct injection, but they are disadvantageous in that they can not be used in tissues that are subjected to loads such as bones due to their low mechanical stability. On the other hand, porous scaffolds are widely used for bone regeneration because of their mechanical stability and cell adhesion and tissue regeneration, although they have some limitations in morphological diversity.

Currently, the trend of tissue engineering technology is to fabricate porous scaffolds similar to tissues using biodegradable polymers and inject cells into scaffolds to form a three-dimensional cell / scaffold complex and transplant them into the body.

Generally, porous scaffolds can be prepared by sponge replication, in which a polymer sponge is coated with a calcium phosphate slurry and pyrolyzed with a polymer sponge by a drying process and a heat treatment process. In this case, pyrolysis and pulverization There is a disadvantage that the pores connected to each other are crushed or disappear.

In addition, the precursor may be prepared by mixing the precursor with a foaming agent which generates gas or gas, solidifying it, and then performing a drying process and a sintering process to form pores. In this case, the metal catalyst exhibits toxicity It is not preferable.

To solve this problem, a composition for a porous calcium phosphate powder for physical foaming having a double pore structure and a method for producing the same, which has been studied and invented by the present inventor, is disclosed in Japanese Patent No. 10-1268408, The bubbles are blown up by the rotational force of the impeller due to the physical and mechanical properties of the bubbles generated by stirring with the impeller, so that it is difficult to obtain uniform slurry bubbles such as irregular pore size, shape, structure and pore network, There is a limit in that it is possible to foam only in a water system mainly by using a water-soluble polymer or monomer such as dodecacrylamide.

On the other hand, among the ceramic materials most commonly used as a scaffold, the calcium phosphate system is similar to the components and structures of the bone tissue and teeth, and has been studied as a bone graft material because of its biocompatibility. Among the calcium phosphate ceramics, hydroxyapatite and tricalcium phosphate or biphasic calcium phosphate, which is a mixture of these two phases, have excellent biocompatibility, bone conduction and biodegradability. Research.

Among these, BCP with the most stable HA phase and highly soluble β- TCP phase is used as a successful bone graft substitute in dentistry and orthopedics. These synthetic biodegradable materials vary in their bioabsorbability depending on their physico-chemical properties, and their decomposition rates vary depending on the surface area, microstructure, degree of porosity and crystallinity of the graft.

In general, when the crystallinity is similar and when the particle size of the individual graft material is large, the residence time in the living body is relatively long in relation to the absorption, and if not the dense sintered body, osteolysis due to the macrophage reaction occurs in the formation of wear debris ) Can not be excluded at all.

Although the macropores present in the bone graft itself have been known to play a positive role in bone regeneration, the greater the size or number of micropores of the bone graft itself, the lower the strength of the bone filler It is known that besides the porous structure, the bone graft composition and the surface morphology of the micron unit are important factors affecting bone regeneration.

Recent studies have emphasized the importance of micron-sized microporous structures associated with surface properties of bone graft materials. In other words, the micropores having a diameter of 10 μm or less can facilitate the circulation of body fluids into bone graft materials, affecting dissolution and degradation, promoting protein adsorption, cell adhesion and mineralization during bone regeneration, It is known to be one of the surface properties.

KR 10-2013-0009477 A (2013.01.23) KR 10-2013-0079791 A (2013.07.11) KR 10-2014-0056422 A (2014.05.12) KR 10-0486367 B1 (Apr. 21, 2005) KR 10-0401941 B1 (2003.10.02) KR 10-1230704 B1 (2013.01.31) KR 10-1268408 B1 (2013.05.22)

Porous scaffold for tissue engineering, Sang - Heon Kim, Soo - Hyun Kim, Young - Ha Kim. Polymer Science and Technology Vol. 16, No. 4 (2005. 8) pp.468-477 1225-0260.

Accordingly, the inventors of the present invention focused on solving the limitations and problems of the conventional porous scaffold composition and the physical foaming method using the same, taking into consideration the above-mentioned matters in a comprehensive manner, and forming and polymerizing a uniform calcium phosphate foam by a physical method , And a new porous scaffold composition and a method for producing the porous scaffold composition which are excellent in uniformity and interconnection of pores and capable of obtaining good osseointegration performance and effects and sintering the same have been extensively studied. As a result, It was invented.

Accordingly, it is a technical object of the present invention to provide a porous scaffold composition and a method of manufacturing the porous scaffold composition which can have a uniform pore structure with improved osseointegration performance.

Herein, the technical object and object to be solved by the present invention are not limited to the above-mentioned technical object and purpose, but another technical object and purpose not mentioned can be understood by those skilled in the art from the following description.

In order to accomplish the objects and the objects of the present invention, there is provided a method of manufacturing a semiconductor device, comprising: 1) 45 to 58 wt% of a calcium phosphate powder; 2) 40 to 50% by weight of at least one water-based monomer selected from N-hydroxymethyl acrylamide and N, N-methylenebisacrylamide; 3) 0.6 to 1.5% by weight of polyoxyethylene sorbitan monooleate (Tween 80); 4) 0.8 to 2% by weight of one kind of anionic surfactant selected from the group consisting of alkyl sulfate and alkyl ether sulfate; 5) 0.2 to 0.5% by weight of one kind of dispersing agent selected from ammonium polycarboxylic acid salts and sodium polycarboxylic acid; and a porous scaffold composition.

As a result, the uniformity of the pores and the interconnectivity are excellent, and a good fusion-fusion performance and effect can be obtained.

Specific means according to the second embodiment of the present invention are 1) 45 to 58% by weight calcium phosphate powder; 2) a polymer selected from the group consisting of urethane acrylate, aliphatic urethane acrylate, epoxy acrylate, methyl methacrylate, ethyl methacrylate, hydroxyethyl ethyl acrylate, methacrylate, silicone acrylate, silicone diacrylate, polyester acrylate, polyether acrylate, hexakis methoxy methyl melamine, 30 to 40% by weight of at least one non-aqueous monomer selected from the group consisting of epoxy resin, hexandediol acrylate, and tripropylene glycol diacrylate; 3) 0.2 to 1.5% by weight of polyoxyethylene sorbitan monooleate (Tween 80); 4) 0.8 to 3% by weight of polydimethylsiloxane; 5) 5 to 15% by weight of ethyl alcohol, based on the total weight of the porous scaffold.

As a result, the uniformity of the pores and the interconnectivity are excellent, and a good fusion-fusion performance and effect can be obtained.

A concrete means according to the third embodiment of the present invention is characterized in that A) a container containing a calcium phosphate slurry constituted by the composition ratio of the first or second aspect is arranged with a sponge impregnated with the calcium phosphate slurry The calcium phosphate slurry foam obtained by the step A is cured by an emulsion polymerization reaction, and the calcium phosphate slurry obtained by the step A is cured by an emulsion polymerization reaction C) drying the calcium phosphate slurry foam obtained through the B process in a drier at 30 to 60 ° C for 3 to 24 hours, D) drying the calcium phosphate slurry foam through the C process, Heated to 600 ° C at a heating rate of 1 to 5 ° C / min, held for 1 to 5 hours, reheated to a temperature of 1100 to 1200 ° C at a heating rate of 1 to 5 ° C / min, Process, E) sintering was maintained for proposes a porous scaffold characterized in that comprising a step of classifying sieve of 0.5 ~ 2mm mesh (mesh) and then pulverized to a calcium phosphate slurry sintered body obtained through the D process.

This makes it possible to efficiently and stably produce a porous scaffold that is excellent in uniformity of pores and interconnectivity, and can obtain good fusion-bonding performance and effect.

An embodiment of the present invention having the means and structure for achieving the object and solution of the technical object as described above is characterized in that the physical shrinkage and expansion are repeated in a state where the sponge is impregnated with the calcium phosphate slurry, And then polymerized and sintered to obtain a porous calcium phosphate slurry foam having excellent macro-pores of 200-400 microns and micropores of 0.5-10 microns, which are excellent in mutual connectivity, and thereby, when placed in a human body, Can be easily introduced and adhered, thereby realizing a good osseointegration performance as well as greatly improving the occupancy rate of the autogenous bone during the bone regeneration process.

Here, the effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned can be clearly understood by those skilled in the art from the description of the claims.

1 is a longitudinal sectional view schematically showing an apparatus for manufacturing a porous scaffold according to an embodiment of the present invention.
FIG. 2 is a photograph of a porous scaffold according to a first preferred embodiment of the present invention photographed by a scanning electron microscope and magnified 50 times. FIG.
FIG. 3 is a photograph of a porous scaffold according to a comparative example for comparison with the first embodiment of the present invention, magnified 50 times by scanning with a scanning electron microscope.
FIG. 4 is a photograph of a porous scaffold according to a second preferred embodiment of the present invention, magnified 50 times by scanning with a scanning electron microscope.
FIG. 5 is a photograph of a porous scaffold according to a comparative example for comparison with the second embodiment of the present invention, magnified 50 times by scanning with a scanning electron microscope.

Hereinafter, embodiments according to the present invention will be described more specifically with reference to the accompanying drawings.

Prior to this, the following terms are defined in consideration of the functions of the present invention, and they are to be construed to mean concepts that are consistent with the technical idea of the present invention and interpretations that are commonly or commonly understood in the technical field of the present invention.

In the following description, well-known functions or constructions are not described in detail to avoid obscuring the subject matter of the present invention.

Hereinafter, the attached drawings are exaggerated or simplified in order to facilitate understanding and clarification of the structure and operation of the technology, and it is to be understood that each component does not exactly coincide with the actual size.

In addition, when a part includes an element, it does not exclude other elements unless specifically stated otherwise, but may include other elements.

As shown in FIG. 1, an apparatus for manufacturing a porous scaffold according to an embodiment of the present invention includes a closed container 10 capable of containing a predetermined amount of calcium phosphate slurry S, A mesh plate 20 having a predetermined thickness and having a plurality of through holes arranged at predetermined intervals and a mesh plate 20 disposed between the mesh plate 20 and the bottom of the container 10, A polyurethane sponge 30 having a certain thickness impregnated with calcium phosphate slurry S contained in the sponge 30 and a calcium phosphate slurry S foamed due to the contraction and expansion action of the sponge 30 according to the elasticity, And an actuator 40 for physically pressing and pressing the sponge 30 by vertically reciprocating the mesh plate 20 so as to generate the sponge 30.

Here, the actuator 40 may employ a solenoid capable of performing an ascending and a descending operation while switching its opening and closing operation by an electromagnetic force that converts electrical energy into magnetic energy in accordance with a control signal of the control section. Alternatively, And a cam device for converting the rotational motion of the motor into the linear motion by using a conventional actuator mechanism or cam having a structure of moving up or down when the cylinder rod is operated by hydraulic pressure or air pressure It is needless to say that various apparatuses that reciprocate vertically can be used by those skilled in the art.

Manufacture of aqueous calcium phosphate slurry

40 to 50% by weight of N-hydroxymethyl acrylamide or N, N-methylenebisacrylamide is preferably used as a polymerization binder in the agitator, preferably N-hydroxymethyl acrylamide 45 By weight, and 0.2 to 0.5% by weight of a polycarboxylic acid ammonium salt or a polycarboxylic acid sodium salt, preferably 0.3% by weight of a polycarboxylic acid ammonium salt, is added as a dispersant.

0.6 to 1.5% by weight, preferably 1% by weight, of a liquid type polyoxyethylene sorbitan monooleate (Tween 80) is added as a main surfactant, and as a co-surfactant, type alkyl sulfates or alkyl ether sulfates in an amount of 0.8 to 2% by weight, preferably 1.5% by weight in the case of alkyl ether sulfates, 58% by weight, preferably 50% by weight, of the calcium phosphate slurry is slowly and homogeneously mixed until completely dissolved to prepare a calcium phosphate slurry.

At this time, the main surfactant and the co-surfactant, which induce the foaming to occur easily by lowering the surface tension of the slurry, are liquid type, dissociated into ions in the water system to increase the degree of hydrophilization, The bubbles can be well formed and the pores can be uniformly formed. That is, when only the main surfactant is used alone, the foam is well formed, but the size is large and unevenly formed, and the strength after the polymerization and drying is too thin.

When the calcium phosphate powder is less than 45% by weight, the viscosity of the slurry is low and the fluidity of the calcium phosphate powder is excellent. Therefore, the calcium phosphate powder can easily generate bubbles in the physical process due to the elastic action of the sponge 30 Although the porosity is greatly increased, there is a disadvantage in that the strength is lowered after molding and heat treatment. When the content exceeds 58 wt%, the strength is sufficiently large due to the high solid content of the powder, but the pore ratio is deteriorated.

As the calcium phosphate powder, it is preferable to use at least one selected from hydroxyapatite, beta-tricalcium phosphate (BCP), and biphasic calcium phosphate.

On the other hand, an emulsion polymerization process is required to foam the calcium phosphate slurry and then harden the calcium phosphate slurry bubble.

As a curing agent therefor, ammonium peroxodisulphate, ammonium persulfate, sodium persulfate, potassium persulfate, tetramethylenediamine, diethylenetriamine ) And triethylenetetramine may be selected and added in an amount of 1 to 5% by weight based on the total weight ratio of the calcium phosphate slurry foam.

Preferably, ammonium peroxodisulfate having a concentration of 33% is diluted with distilled water, and 3% by weight of ammonium peroxodisulfate is added to the foamed calcium phosphate slurry foam in a proportion of the total weight of the calcium phosphate slurry foam. The resulting mixture is stirred evenly and then diluted with distilled water Tetramethylenediamine having a concentration of 33% is added in an amount of 3% by weight based on the total weight ratio of the calcium phosphate slurry foam, and the mixture is allowed to stand for about 10 minutes.

Non-aqueous system  Manufacture of calcium phosphate slurry

In the agitator, urethane acrylate, aliphatic urethane acrylate, epoxy acrylate, methyl methacrylate, ethyl methacrylate, hydroxyethyl ethyl acrylate, methacrylate, silicone acrylate, silicone diacrylate, polyester acrylate, polyether acrylate, hexakis methoxy methyl melamine, 30 to 40% by weight of at least one non-aqueous monomer selected from the group consisting of an epoxy resin, hexandediol acrylate and tripropylene glycol diacrylate, And 35 weight% of acrylate (urethane acrylate).

Then, 5 to 15% by weight, preferably 10% by weight, of ethyl alcohol is added as a dissolving agent, 0.2 to 1.5% by weight of polyoxyethylene sorbitan monooleate (tween 80) as a main surfactant, By weight of calcium phosphate powder is added, and 1.2 to 3% by weight of polydimethylsiloxane is added as an auxiliary surfactant, preferably 45 to 58% by weight, preferably 50 to 50% by weight, After the weight% is added, the slurry is slowly and homogeneously mixed until completely dissolved to prepare a non-aqueous calcium phosphate slurry.

If the content of urethane acrylate is more than 40% by weight based on the total composition ratio, the viscosity of the slurry becomes high and bubbles hardly occur and pores are not uniformly formed. When the content of urethane acrylate is less than 30% by weight, Foaming does not occur well.

If the content of polyoxyethylene sorbitan monooleate (Tween 80) exceeds 1.5% by weight based on the total composition ratio, the pores are not uniform. If the content is less than 0.2% by weight, the surface tension of the slurry is lowered Do not bubble well.

If the content of polydimethyloyloxane exceeds 3 wt% based on the total composition ratio, the viscosity of the slurry becomes high and bubbles do not easily occur. When the content of polydimethylsiloxane is less than 0.8 wt%, the surface tension is not lowered, .

If the content of the calcium phosphate powder is more than 58 wt% based on the total composition ratio, the slurry is not foamed well. If the calcium phosphate powder is less than 45 wt%, the strength of the final product falls.

On the other hand, an emulsion polymerization process is required to foam the calcium phosphate slurry and then harden the calcium phosphate slurry bubble.

As a curing agent therefor, ammonium peroxodisulphate, ammonium persulfate, sodium persulfate, potassium persulfate, tetramethylenediamine, diethylenetriamine ) And triethylenetetramine may be selected and added in an amount of 1 to 5% by weight based on the total weight ratio of the calcium phosphate slurry foam.

Preferably, ammonium peroxodisulfate having a concentration of 33% is diluted with distilled water, and 3% by weight of ammonium peroxodisulfate is added to the foamed calcium phosphate slurry foam in a proportion of the total weight of the calcium phosphate slurry foam. The resulting mixture is stirred evenly and then diluted with distilled water Tetramethylenediamine having a concentration of 33% is added to the slurry in an amount of 3% by weight based on the total weight of the slurry of the calcium phosphate slurry, followed by stirring, followed by allowing to stand for about 10 minutes.

Calcium phosphate slurry foaming

First, a 60 ppi (pores per inch) polyurethane sponge (30) was immersed in an ultrasonic water bath containing 10% sodium hydroxide solution for 10 minutes, then washed in running water, then immersed in distilled water for 10 minutes in a supersonic water bath, do.

Subsequently, as shown in FIG. 1, a predetermined amount of the calcium phosphate slurry S is placed in the closed container 10, and the aqueous or non-aqueous calcium phosphate slurry is put on the sponge 30 with the sponge 30 placed thereon. The actuator 40 is operated in a state where the mesh plate 20 is positioned on the sponge 30 so that the sponge 30 is uniformly impregnated into the inside of the sponge 30. The mesh plate 20 reciprocates upward and downward, Lt; / RTI > The calcium phosphate slurry S is foamed by the contraction and expansion action of the sponge 30 due to the elasticity of the sponge 30 and the foam B generated at this time is raised to the upper side of the container 10 through the through hole of the mesh plate 20 .

Calcium phosphate slurry bubble hardening

The calcium phosphate slurry bubbles are transferred into a separate mold-type container and cured by emulsion polymerization reaction.

To this end, ammonium peroxodisulphate, ammonium persulfate, sodium persulfate, potassium persulfate, tetramethylenediamine, diethylenetriamine, diethylenetriamine, Triethylenetetramine is added in an amount of 1 to 5% by weight based on the total weight ratio of the calcium phosphate slurry foam, followed by stirring.

Preferably, ammonium peroxodisulfate having a concentration of 33% is diluted with distilled water, and 3% by weight of ammonium peroxodisulfate is added to the calcium phosphate slurry foam in a proportion of the total weight of the calcium phosphate slurry foam, and the calcium phosphate slurry is uniformly mixed. Tetramethylenediamine having a concentration of 33% was added in an amount of 3% by weight based on the total weight ratio of the calcium phosphate slurry foam, and the mixture was homogeneously mixed and allowed to stand at room temperature for about 10 minutes.

Calcium phosphate slurry Foam  dry

The cured calcium phosphate slurry foam, that is, the calcium phosphate slurry foam is taken out of the container, put in a drier at 30 to 60 ° C, and dried for 3 to 24 hours.

Preferably 60 ° C, and dried for 15 hours.

Calcium phosphate slurry Foam  Sintering

The dried calcium phosphate slurry foam was placed in an alumina crucible and placed in an electric furnace and heated to 600 ° C at a temperature raising rate of 1 to 5 ° C / min, maintained for 1 to 5 hours, heated at a rate of 1 to 5 ° C / After reheating to 1200 ° C, sinter for 2 to 4 hours.

Preferably, the electric furnace is heated at a rate of 1 to 5 占 폚 / min and then heat-treated at 600 占 폚 for 4 hours, then heated again at a rate of 1 to 5 占 폚 / min and heat-treated at 1200 占 폚 for 3 hours to obtain a calcium phosphate slurry sintered body .

Crushing of sintered calcium phosphate slurry

The calcium phosphate slurry sintered body is pulverized with alumina-inducing and pestle and then classified with a sieve of 0.5 to 2 mm mesh to prepare a granular porous scaffold (bone-colored material).

Since the porous scaffold manufactured by this method has macropores of 200-400 탆 and micropores of 0.5-10 탆 at the same time, the inflow of bone cells is facilitated through the macropores, , The bone marrow adherence is favorable, and the autogenous bone share of 70% or more can be obtained.

≪ Example 1 > Scaffold  Produce

45 wt% of N-hydroxymethyl acrylamide was added to the agitator, 0.3 wt% of ammonium polycarboxylate was added, and 1.2 wt% of polyoxyethylene sorbitan monooleate (Tween 80) And 1.4 wt% of alkyl ether sulfate (Alkyl ether sulfate) was added thereto. 52.1 wt% of calcium phosphate powder was added thereto, and then uniformly dispersed to prepare a calcium phosphate slurry. .

The slurry S is placed in the closed container 10 and the actuator 40 is operated in a state where the sponge 30 and the mesh plate 20 are placed on the slurry S, The sponge 30 was repeatedly pressed and pressed so that the calcium phosphate slurry S was foamed to form an aqueous calcium phosphate slurry foam.

The thus obtained calcium phosphate slurry bubble was transferred into a separate mold-type vessel, and ammonium peroxodisulfate having a concentration of 33% was added to the calcium phosphate slurry bubble in an amount of 3 wt% based on the total weight ratio of the calcium phosphate slurry bubble Tetramethylenediamine having a concentration of 33% was added thereto in an amount of 3% by weight based on the total weight ratio of the calcium phosphate slurry foam, and the mixture was homogeneously mixed and cured by standing at room temperature for about 10 minutes.

Subsequently, the cured calcium phosphate slurry foam was taken out from the mold-type container, dried in a dryer kept at 60 ° C., and dried for 15 hours. Then, it was placed in an alumina crucible and placed in an electric furnace. The electric furnace was heated at a rate of 1 to 5 ° C./min, For 4 hours, then heated at a rate of 1 to 5 ° C / min and heat-treated at 1200 ° C for 3 hours to obtain a calcium phosphate slurry sintered body. The mixture was pulverized with alumina-inducing agent and pestle and then classified with a 1 mm mesh sieve to prepare a granular porous scaffold (bone-biased material).

The photomicrograph of FIG. 2, which is magnified 50 times by photographing the thus prepared Example 1 with a scanning electron microscope, shows that macropores having a size of 200 to 400 μm are uniformly formed.

≪ Comparative Example 1 > Scaffold  Produce

50% by weight of N-hydroxymethyl acrylamide was added to the agitator, 0.3% by weight of ammonium polycarboxylate was added and 0.6% by weight of polyoxyethylene sorbitan monooleate (Tween 80) , And calcium phosphate powder (49.1 wt%) was added thereto. The mixture was slowly and uniformly mixed until uniformly dispersed to prepare a calcium phosphate slurry.

A granular porous scaffold (bone-colored material) was prepared in the same manner as in Example 1 above using the thus prepared aqueous calcium phosphate slurry (S).

3, which was magnified 50 times by photographing with the scanning electron microscope of Comparative Example 1 thus produced, shows a phenomenon in which the skeleton is broken and collapsed due to large bubbles, and since the skeletons are not connected to each other, It can be seen that it breaks apart and breaks easily.

≪ Example 2 > Non-aqueous system  Using a calcium phosphate slurry Scaffold  Produce

35% by weight of urethane acrylate resin was added to a stirrer, 10% by weight of ethyl alcohol for dissolution was added thereto, and liquid type polyoxyethylene sorbitan monooleate (Tween 80) was added as a surfactant, 1.2% by weight of polydimethylsiloxane and 1.7% by weight of polydimethylsiloxane were fed into the flask and 52.1% by weight of calcium phosphate powder was added thereto. The mixture was slowly and uniformly mixed until uniformly dispersed to prepare a nonaqueous calcium phosphate slurry.

The thus prepared nonaqueous calcium phosphate slurry S is placed in a hermetically sealed container 10 and the actuator 40 is operated in a state in which the sponge 30 and the mesh plate 20 are sequentially placed thereon to form the mesh plate 20 ) Repeatedly pressurized and squeezed the sponge 30 to foam the calcium phosphate slurry S to form a non-aqueous calcium phosphate slurry foam.

The thus obtained calcium phosphate slurry bubble was transferred into a separate mold-type vessel, and ammonium peroxodisulfate having a concentration of 33% was added to the calcium phosphate slurry bubble in an amount of 3 wt% based on the total weight ratio of the calcium phosphate slurry bubble Tetramethylenediamine having a concentration of 33% was added thereto in an amount of 3% by weight based on the total weight ratio of the calcium phosphate slurry foam, and the mixture was homogeneously mixed and cured by standing at room temperature for about 10 minutes.

Subsequently, the cured calcium phosphate slurry foam was taken out from the mold-type container, dried in a dryer kept at 60 ° C., and dried for 15 hours. Then, it was placed in an alumina crucible and placed in an electric furnace. The electric furnace was heated at a rate of 1 to 5 ° C./min, For 4 hours, then heated at a rate of 1 to 5 ° C / min and heat-treated at 1200 ° C for 3 hours to obtain a calcium phosphate slurry sintered body. The mixture was pulverized with alumina-inducing agent and pestle and then classified with a 1 mm mesh sieve to prepare a granular porous scaffold (bone-biased material).

FIG. 4, which is magnified 50 times by photographing the thus prepared Example 2 with a scanning electron microscope, shows that macro pores having a size of 200 to 400 μm are uniformly formed.

≪ Comparative Example 2 & Non-aqueous system  Using a calcium phosphate slurry Scaffold  Produce

40% by weight of urethane acrylate resin was added to a stirrer, 10% by weight of ethyl alcohol was added thereto for dissolution thereof, and liquid type polyoxyethylene sorbitan monooleate (Tween 80) was added as a surfactant. 0.6% by weight of calcium phosphate powder was added thereto, and 49.4% by weight of calcium phosphate powder was added thereto. The mixture was slowly and uniformly mixed until uniformly dispersed to prepare a nonaqueous calcium phosphate slurry.

A granular porous scaffold (bone-colored material) was prepared in the same manner as in Example 2 above using the thus prepared non-aqueous calcium phosphate slurry (S).

5, which was magnified 50 times by photographing with the scanning electron microscope, a bubble of a size of several millimeters resulted in breakage and collapse of the skeleton during polymerization, and the skeletons were not connected to each other, As a result, the strength is remarkably reduced and it is easily broken.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments or constructions. Various changes and substitutions may be made without departing from the spirit and scope of the invention. It will be obvious to those skilled in the art that the present invention can be widely applied to other embodiments.

Therefore, it is to be understood that modifications and variations of the features of the present invention are intended to be included within the spirit and scope of the present invention.

10: vessel 20: mesh plate
30: Sponge 40: Actuator
S: calcium phosphate slurry B: calcium phosphate slurry foam

Claims (5)

1) 45 to 58% by weight of calcium phosphate powder;
2) 40 to 50% by weight of at least one water-based monomer selected from N-hydroxymethyl acrylamide and N, N-methylenebisacrylamide;
3) 0.6 to 1.5% by weight of polyoxyethylene sorbitan monooleate (Tween 80);
4) 0.8 to 2% by weight of one kind of anionic surfactant selected from the group consisting of alkyl sulfate and alkyl ether sulfate;
5) 0.2 to 0.5% by weight of one kind of dispersant selected from ammonium polycarboxylate and sodium polycarboxylate;
Lt; RTI ID = 0.0 > 1, < / RTI >
1) 45 to 58% by weight of calcium phosphate powder;
2) a polymer selected from the group consisting of urethane acrylate, aliphatic urethane acrylate, epoxy acrylate, methyl methacrylate, ethyl methacrylate, hydroxyethyl ethyl acrylate, methacrylate, silicone acrylate, silicone diacrylate, polyester acrylate, polyether acrylate, hexakis methoxy methyl melamine, 30 to 40% by weight of at least one non-aqueous monomer selected from the group consisting of epoxy resin, hexandediol acrylate, and tripropylene glycol diacrylate;
3) 0.2 to 1.5% by weight of polyoxyethylene sorbitan monooleate (Tween 80);
4) 0.8 to 3% by weight of polydimethylsiloxane;
5) 5 to 15% by weight of ethyl alcohol;
Lt; RTI ID = 0.0 > 1, < / RTI >
3. The method according to claim 1 or 2,
6) Ammonium peroxodisulphate, ammonium persulfate, sodium persulfate, potassium persulfate, tetramethylenediamine, diethylenetriamine, diethylenetriamine, 1 to 5% by weight of at least one curing agent selected from triethylenetetramine;
≪ / RTI >
A method for manufacturing a porous scaffold comprising the steps of:
A) A sponge impregnated with the calcium phosphate slurry is placed in a container containing the calcium phosphate slurry having the composition ratio of claim 1 or 2, and a mesh plate having apertures arranged at regular intervals is sequentially placed thereon. A process of foaming the calcium phosphate slurry by shrinking and expanding the sponge by reciprocating motion
B) a step of curing the calcium phosphate slurry bubble obtained by the step A by an emulsion polymerization reaction
C) a step of drying the calcium phosphate slurry foam obtained through the step B in a drier at 30 to 60 ° C for 3 to 24 hours
D) The calcium phosphate slurry foam dried through step C is placed in an alumina crucible and placed in an electric furnace. The slurry is heated to 600 ° C at a temperature rising rate of 1 to 5 ° C / min, maintained for 1 to 5 hours, min to a temperature of 1100 to 1200 ° C, and then sintered by maintaining the temperature for 2 to 4 hours
E) Grinding the sintered calcium phosphate slurry obtained through the above-mentioned step D, and then classifying it into a sieve of 0.5 to 2 mm mesh
5. The method of claim 4,
The step B may be carried out for the emulsion polymerization using ammonium peroxodisulphate, ammonium persulfate, sodium persulfate, potassium persulfate, tetramethylenediamine, di 1 to 5% by weight of at least one curing agent selected from ethylene triamine, diethylenetriamine and triethylenetetramine is added to the calcium phosphate slurry foam obtained through the step A, and stirred to prepare a porous scaffold Way.

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