KR100751504B1 - Nano-macro sized porous biomaterials with 3-d hierarchical pore structure and method for prepararion thereof - Google Patents

Abstract

A nano-macro sized porous biomaterials with a 3-D hierarchical pore structure and a method for preparation thereof are provided to obtain a functional support body which is biodegradable and has high cell inducing capacity economically. Calcium and phosphorus are dispersed evenly among silicon in a polyurethane high polymer sponge, and a biomaterial is coated thereon to form the nano-macro sized porous biomaterials with a 3-D hierarchical pore structure in which macro pores in a range of 1-1,000 micrometers and nano-pores in a range of 1-100nm are formed to be connected to each other by a two dimensional and three dimensional hierarchical pore structure. Nano pores in a range of 1-100nm are formed by a structure inducing agent on the biomaterials. The nano pore structure inducing agents are cationic and nonionic surfactants.

Description

Nano-Macro sized Porous Biomaterials with 3-D Hierarchical Pore Structure and Method for Prepararion

1 is a schematic diagram of a method for synthesizing a porous biomaterial of a hierarchical pore structure of nano-macro size according to the present invention;

FIG. 2 is an optical microscopy photograph of a porous biomaterial obtained by using a polyurethane sponge (left), a block copolymer, and a polyurethane sponge according to an embodiment of the present invention;

3 is a graph showing small-angle X-ray diffraction (XRD) measurement results of porous biomaterials for block copolymers F127 and P123 according to an embodiment of the present invention;

4 is a transmission electron microscopy (TEM) photograph and an optical microscope (bottom) photograph of a porous biomaterial for a block copolymer (F127 (left), P123 (right)) according to an embodiment of the present invention;

5 is an example in which a synthesis method according to an embodiment of the present invention and a conventional synthesis method are compared; And

6 is an optical microscope (A), scanning electron microscopy (SEM, (B, C)), and transmission electron microscope of a porous biomaterial using a surfactant and a polyurethane sponge according to an embodiment of the present invention (D) Photo.

The present invention relates to a biomaterial having a hierarchical pore structure of nano-macro size and a method for synthesizing it. In particular, the present invention relates to a biomaterial having a hierarchical pore structure of various nano-macro sizes as a functional bone restorative material, a bone support, etc., which is composed of open pores interconnected with nano and macro pores, and a method for synthesizing the same.

A great deal of attention has been focused on regenerative medicine, which is attracting attention as the next generation of medical technologies, in particular, artificially forming tissues by separating and culturing cells from tissues to be regenerated and inoculating them into appropriate biomaterials. Such a procedure requires an appropriate cell support to prevent separation from connective tissue after transplantation, and the development of a support that is excellent in tissue adhesion and cell adhesion.

Conventionally, a polymer support is widely used as a cell support, but as bone regeneration material for bone loss, calcium phosphate-based ceramic materials such as hydroxyapatite and tricalcium phosphate, polymer-ceramic due to mechanical strength, affinity with bone, etc. Ceramic materials such as composites, bioglass, and calcium carbonate are typically used. In addition, the bone support preferably has an open pore structure connected in three dimensions for efficient bone formation. In the method of synthesizing the ceramic material into a support having three-dimensional pores, the ceramic fine powder is slurried, coated on a polymer support such as polyurethane, and then the polyurethane is removed and porousized by heat treatment. 0331990), a method using a multiple compression process (Lee Byung-Tak et al. 3, J. Kor . Ceram . Soc , 2004, 41, 2004), a method of manufacturing by contacting spherical ceramic particles with each other (Korea Patent Publication No. 2003-0023568 ) And polyvinyl butyral (DMLiu, Biomaterials , 1955, 17, 1996) or methyl cellulose (NOEngin et al. 1, J. Eur . Ceram . Soc ., 2569, 19, 1009) And a method of producing a mixture thereof. However, all of them are supports that have macrosized pores (tens of hundreds to hundreds of micros) connected in series, but they do not control the structure of the ceramic walls that make up the pores, so that they are only biocompatible but have little histological bone induction. It was confirmed that after the procedure frequently separated from the bone tissue by the interposition of connective tissue. In addition, these ceramic walls have no functionality other than just being used as a cell attachment site. In addition to the excellent biocompatibility, there is a need for a functional ceramic implant that is excellent in bone induction and bone adhesion, and can be properly absorbed and replaced with regenerated bone when transplanted.

If the ceramic walls of the three-dimensional support, which form macroscopic pores, are composed of nano-sized interconnected pores, the specific surface area and porosity will be increased, cell adhesion will be enhanced, and growth factors or nutrients, oxygen, drugs in the nano-sized pores. Adsorption, etc. may be expected to improve cell proliferation, differentiation, and reduce cell necrosis in the scaffold, a problem of three-dimensional structures. In addition, by adsorbing and using drugs such as anticancer drugs and anti-inflammatory drugs, it is expected that a role of a functional supporter that plays a role of bone regeneration and healing of inflammation and the like can be possible. As a method of synthesizing the nano-sized pores, it is considered that the polymer template method (CTKresge et al. 4, Nature , 710, 359, 1992) that provides easy control of pore size and structure and provides a large specific surface area is effective. By applying the method and the above-described three-dimensional support synthesis technique together, it is thought that the support of nano and macro sized pores can be synthesized.

Accordingly, the present invention provides a porous biological body formed of a three-dimensional hierarchical pore structure in which nanosized and macrosized pores are interconnected and have open pores in order to provide a functional support that is biocompatible, biodegradable and has high cell induction. The purpose is to provide the material.

In addition, an object of the present invention is to provide a method for synthesizing a bio-material of nano-macro size hierarchical pore structure having open pores interconnected.

In order to achieve the above technical problem, the present invention is a polyurethane polymer sponge having a macro-pore structure in the range of 1 to 1000 μm, calcium and phosphorus are uniformly dispersed in silicon and in the range of 1 to 100 nm by a structure inducing agent A nano-macro size formed by coating a biomaterial having nano pores formed thereon so that macro pores in a range of 1 to 1000 μm and nano pores in a range of 1 to 100 nm are interconnected in a two-dimensional and three-dimensional hierarchical pore structure. It provides a biomaterial having a hierarchical pore structure of.

In addition, the present invention comprises the steps of (a) dissolving the block copolymer of polyethylene oxide and polypropylene oxide in an organic solvent containing alcohol to synthesize a block copolymer template solution, (b) silicon compounds, calcium compounds and phosphorus compounds Synthesizing a biomaterial solution by mixing, (c) adding the biomaterial solution to the block copolymer template solution to obtain a precursor solution, and (d) depositing and drying a polyurethane polymer sponge in the precursor solution. And (e) calcining the dried material obtained in (d) to remove residual organic material and the template, thereby providing a method for synthesizing a biomaterial having a hierarchical pore structure of nano-macro size.

In addition, the present invention comprises the steps of (a) dissolving a surfactant in an organic solvent containing ammonia water to synthesize a surfactant template solution, (b) mixing a silicon compound in the surfactant template solution to obtain a sol precursor solution (C) dipping and drying the polyurethane polymer sponge in the sol solution obtained in step (b), and (d) firing the dried product obtained in step (c) to remove residual organic materials and the template. Provided is a method for synthesizing a biomaterial having a hierarchical pore structure of nano-macro size.

Hereinafter, the present invention will be described in detail.

The present invention relates to a polyurethane material sponge having a macropore structure in the range of 1 to 1000 μm, wherein the biomaterial is formed by dispersing calcium and phosphorus in silicon uniformly and forming nano pores in the range of 1 to 100 nm by a structure inducing agent. A coating is formed to form a nano-macro-sized hierarchical pore structure in which macropores in a range of 1 to 1000 μm and nanopores in a range of 1 to 100 nm are interconnected in a two-dimensional and three-dimensional hierarchical pore structure. Include.

Specifically, the present invention uses a polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymer and a polyurethane polymer sponge as a structure directing agent in order to obtain a support shape interconnected in a two-dimensional and three-dimensional hierarchical pore structure. Bio-materials having a hierarchical pore structure of nano-macro size, including nanopores in the range of 1 to 100 nm and macropores in the range of 1 to 1000 μm, are used as heterogeneous organic templates of different sizes.

Here, the template for the covalent degree of use is not limited to block copolymers of polyethylene oxide-polypropylene oxide-polyethylene oxide, and block copolymers of various structures may be used as the template.

Nanoporous structure of the porous biomaterial is preferably formed of open pores interconnected in two and three dimensions. Two-dimensional and three-dimensional pore structures are formed by organic templates that form self-organizing structures such as block copolymers, and nano-size open pores form regular structures such as two-dimensional or three-dimensional hexagonal and cubic crystals. It refers to the connected shape. In order to use the macropore structure of the porous biomaterial as a support of a cell, a shape in which pores are connected in a three-dimensional direction (x, y, z-axis directions) is required. The hierarchical pore structure refers to a pore structure in which regular pores of different size regions are interconnected. The block copolymer and polyurethane sponge are decomposed and removed by firing or solvent extraction, respectively. It means to remain as pore.

The frame constituting the macrosize pores of the hierarchical pore structure is preferably made of pores having the regularity of the nano-size. In this case, a ceramic support having an increased specific surface area and porosity can be obtained, and in addition, the cell adhesion can be improved during implantation in vivo, and body fluid can move freely between the pores.

Adsorption of proliferation factors or nutrients, oxygen, drugs, etc. to the pores of the nano-size can improve cell proliferation and differentiation, and reduce cell necrosis in the support, which is a problem of the three-dimensional structure. By adsorbing and using the drug, it can be used as a functional support that plays a role of bone regeneration and healing of inflammation and the like.

The pore size and structure of the porous biomaterial can be easily controlled according to the molecular weight and structure of each organic material used as a template. As mentioned above, heterogeneous templates of different sizes can be simultaneously used for nanosize (1-100 nm) and macrosize (1-1000 μm).

In particular, the structural inducing agent template for inducing the nano-sized pores may be a surfactant selected from CTAB (cetyltrimethylammonium bromide) or CTAC (cetyltrimethylammonium chloride), or a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide. . The block copolymer is F127 ((polyethylene oxide) 100 (polypropylene oxide) 65 (polyethylene oxide) 100, BASF), F108 ((polyethylene oxide) 133 (polypropylene oxide) 50 (polyethylene oxide) 133, BASF), F98 ((polyethylene oxide) 118 (polypropylene oxide) 44 (polyethylene oxide) 118, BASF), F88 ((polyethylene oxide) 104 (polypropylene oxide) 39 (polyethylene oxide) 104, BASF), P123 (polyethylene Oxide) 20 (polypropylene oxide) 70 (polyethylene oxide) 20, BASF), P105 ((polyethylene oxide) 37 (polypropylene oxide) 56 (polyethylene oxide) 37, BASF), P104 ((polyethylene oxide) 27 (polypropylene Oxide) 61 (polyethylene oxide) 27, BASF) is preferably a pluronic or tetronic block copolymer selected from the group consisting of. Among them, when CTAB is used as a template, porous nanopowders having hexagonal or cubic nanopores having a pore size of 2 to 3 nm can be obtained. When F127 is used as a template, three-dimensional cubic crystals of 5 to 10 nm are used. When cubic nanopores are used for P123, a porous biomaterial having two-dimensional hexagonal nanopores of 5-10 nm can be obtained.

In addition, the present invention comprises the steps of (a) dissolving the block copolymer of polyethylene oxide and polypropylene oxide in an organic solvent containing alcohol to synthesize a block copolymer template solution, (b) silicon compounds, calcium compounds and phosphorus compounds Synthesizing a biomaterial solution by mixing, (c) adding the biomaterial solution to the block copolymer template solution to obtain a precursor solution, and (d) depositing and drying a polyurethane polymer sponge in the precursor solution. And (e) firing the dried material obtained in (d) to remove residual organic material and the template.

In the present invention, when forming nano-sized and macrosized pores simultaneously, it is preferable to use a composite synthesis technique using a polymer template method and a sol-gel method together. First, a precursor solution is prepared by mixing a polymer template that induces nano-sized pores and other elements including silica to form an inorganic wall in a sol-gel reaction. Next, by depositing another template that induces macro-sized pores in the solution, and then drying two or three kinds of organic material at the same time by firing or solvent extraction method through a three-dimensional porous biological body having a desired pore size and structure The materials can be synthesized (see FIG. 1 ).

The step (a) is a step of synthesizing the block copolymer template solution by dissolving the block copolymer in an organic solvent containing alcohol, the block copolymer template has a structure of polyethylene oxide-polypropylene oxide-polyethylene oxide Poloxamer may be used, and the poloxamer used herein refers to a pluronic or tetronic polymer having a hydrophilic group and a hydrophobic group. Among these, hydrophilic polymer blocks such as Pluronic, Tetronic, Reverse Pluronic, or Reverse Tetronic, which have a ratio of F127, F108, F98, F88, P123, P105, P104 and polyethylene / polypropylene of 0.1 to 0.8, and hydrophobic Block copolymers composed of polymer blocks can be used. In this case, F127 may be representatively used to obtain a three-dimensional cubic structure, and P123 may be used to obtain a two-dimensional hexagonal structure.

As the alcohol solvent, those having an alkyl chain having 1 to 25 carbon atoms are preferable. However, it is not limited thereto. The block copolymer template solution may be synthesized by mixing the block copolymer template at a ratio of 10 to 80 mass% with respect to ethanol used as the solvent.

Step (b) is a step of synthesizing the biomaterial solution by mixing the silicon compound, calcium compound and phosphorus compound, using a method of mixing each starting solution at a predetermined interval, or adding an acid or alkaline solution Therefore, calcium and phosphorus may be uniformly dispersed in silica. Even distribution of calcium or phosphorus on the silica can suppress the crystallization generated during the mixing process.

The silicon compound, the calcium compound and the phosphorus compound are Si: Ca: P in an element ratio of 50 to 80:18 to 45: 2 to 10, preferably 75Si: 21Ca: 4P, 65Si: 31Ca: 4P, 55Si: 41Ca A biomaterial solution can be synthesized by mixing at an element ratio of 4 P. It is because it forms stable cubic nanoporous structure in the said range. Especially, it is preferable that the said calcium compound is contained in 10-40 mass% with respect to the said silicon compound, the said calcium compound, and the said phosphorus compound whole quantity. In the concentration range, the formation of the cubic nano-pore structure was confirmed, but the porosity was noticeable at 40% by weight or more, but the pore regular structure was found to be poor.

In the present invention, the silicon compound may be tetraethylorthosilicate, 3-mercaptopropyltrimethoxysilane, 5,6-epoxyhexyltriethoxysilane, etc., and the calcium compound is calcium nitrate tetrahydrate, calcium Nitrate, calcium chloride and the like can be used, and the phosphorus compound may be triethyl phosphate, sodium phosphate and ammonium phosphate dibeix.

The step (c) is a step of obtaining the precursor solution by adding the biomaterial solution to the block copolymer template solution, 700 ~ 1500 revolutions per minute (rpm) and for 2 to 72 hours at 30 ~ 80 ℃ It is preferable to include the step of stirring the mixed solution.

In the present invention, the concentration of the block copolymer template in the mixing step (c) is preferably 30 to 50% by mass, and the concentration of the block copolymer template F127 is TEOS (Tetraethyl orthosilicate) as the biomaterial. When it is 30 mass% or more, the surface irregularities are eliminated and a long period regular structure is formed.

Step (d) is a step of depositing and drying a polyurethane polymer sponge in the precursor solution, the polyurethane polymer sponge provides a regular and interconnected pores of the three-dimensional network. First, the polyurethane polymer sponge may be used by treating the polyurethane polymer sponge with NaOH aqueous solution to surface-modify the polyurethane polymer sponge with hydrophilicity and washing the surface-modified polyurethane polymer sponge with distilled water. At this time, the polyurethane polymer sponge provides a predetermined pore size (30, 45, 60 and 80 ppi). In addition, the pore size of the preferred polyurethane polymer sponge is 20 ~ 60 ppi, the porosity and pore size of the biomaterial is affected by the sponge pore size.

The drying temperature and humidity in the step (d) is preferably -15 ~ 80 ℃, 5 ~ 100 RH%, respectively. The solution may be dried by placing in a constant temperature and humidity chamber for 24 to 72 hours that satisfies the temperature and humidity conditions.

The deposition and drying process of step (d) can be repeated by adjusting the target thickness of the inorganic wall as necessary. Preferably it can be repeated about 1 to 10 times, it is possible to increase the thickness and strength of the ceramic wall forming the macropores by repeated deposition and drying.

Firing the dried material obtained in step (e) to remove residual organic materials and the template, wherein the firing is performed at 600 to 1000 ° C. at a temperature rising rate of 0.2 to 2 ° C./min. Maintaining for 2 to 6 hours to densify and slow cooling the skeleton. Under the firing conditions, F127 or P123 and the polyurethane polymer sponge used as templates can be easily decomposed and removed.

Step (e) is a step of drying the precursor / template solution, the drying temperature and the humidity is preferably -15 ~ 80 ℃, 5 ~ 100 RH%, respectively. The solution may be dried for 1 to 3 hours in a constant temperature and humidity chamber that satisfies the temperature and humidity conditions.

In addition, the present invention comprises the steps of (a) dissolving a surfactant in an organic solvent containing ammonia water to synthesize a surfactant template solution, (b) mixing a silicon compound in the surfactant template solution to obtain a sol precursor solution (C) depositing and drying the polyurethane polymer sponge in the sol solution obtained in step (b), and (d) firing the dried product obtained in step (c) to remove residual organic material and the template. It includes a method for synthesizing a biomaterial having a hierarchical pore structure of nano-macro size.

The step (a) is a step of synthesizing the surfactant template solution by dissolving the surfactant in an organic solvent containing ammonia water, the surfactant may be a cationic and anionic surfactant such as CTAB or CTAC. In the case of biomaterials synthesized using CTAB, it was confirmed that porous materials having a hexagonal pore structure and a pore size of 2 to 3 nm were synthesized.

The step (c) is a step of depositing and drying a polyurethane polymer sponge in the sol solution obtained in (b), the poly to provide a regular and interconnected pores of the three-dimensional network to the template to induce the macro size pores Urethane sponge can be used. First, the polyurethane polymer sponge may be used by treating the polyurethane polymer sponge with NaOH aqueous solution to surface-modify the polyurethane polymer sponge with hydrophilicity and washing the surface-modified polyurethane polymer sponge with distilled water. At this time, the polyurethane polymer sponge provides a predetermined pore size (30 ppi). In addition, the pore size of the preferred polyurethane polymer sponge is 20 ~ 60 ppi, the porosity and pore size of the biomaterial is affected by the sponge pore size.

The drying temperature and humidity in step (d) is preferably -15 ~ 80 ℃, 5 ~ 100 RH%, respectively. The solution may be dried by placing in a constant temperature and humidity chamber for 24 to 72 hours that satisfies the temperature and humidity conditions.

The deposition and drying process of step (d) can be repeated by adjusting the target thickness of the inorganic wall as necessary. Preferably it can be repeated about 1 to 10 times, it is possible to increase the thickness and strength of the ceramic wall forming the macropores by repeated deposition and drying.

Firing the dried material obtained in step (e) to remove residual organic materials and the template, wherein the firing is performed at 600 to 1000 ° C. at a temperature rising rate of 0.2 to 2 ° C./min. Maintaining for 2 to 6 hours to densify and slow cooling the skeleton. Under the firing conditions, CTAB or CTAC and polyurethane polymer sponges used as templates can be easily decomposed and removed.

Hereinafter, the present invention will be described in more detail with reference to Examples and the accompanying drawings. Dean, the following examples and figures are provided to aid the understanding of the present invention, of course, the content of the present invention is not limited or limited by the embodiments of the following drawings.

Example 1 Synthesis of Hierarchical Porous Biomaterials Using F127

In order to induce a cubic three-dimensional nanopore structure, block copolymer Pluronic F127 ((polyethylene oxide) 105 (polypropylene oxide) 65 (polyethylene oxide) 105) was used as a template.

First, F127 (2.88 g) (2.28 g for P123) was added to ethanol (18.1 ml) and stirred for 0.5 to 1 hour until complete dissolution at 40 ° C. At the same time, tetraethylorthosilicate (TEOS) (6 ml) and calcium nitrate tetrahydrate (1.36 g), which are raw materials of biomaterials, were slowly mixed, and triethylphosphate (0.26 ml) was mixed when a uniform solution was produced. Then, a mixture of 1 M hydrochloric acid solution (0.95 ml), ethanol (7.62 ml) and distilled water (2.86 ml) prepared in advance was added and stirred at 40 ° C. for 0.5 to 1 hour until the inorganic starting material was uniformly dissolved ( Solution B). While slowly mixing Solution B with Solution A, the solution was stirred at 40 ° C. for 2 to 72 hours at a strong speed of 700 to 1500 rpm.

The obtained precursor solution was moistened with a predetermined pore size polyurethane sponge (pore size: 30 ppi, 45 ppi, 60 ppi, and 80 ppi) washed through an ultrasonic process, and then carefully taken out, and the temperature was -15 to 80 ° C. and 5 to 100 RH%. It was dried for 1 hour in a humidifier. After drying again, the precursor solution was quickly wetted and dried. The process of deposition and drying was repeated four times. The deposition and drying process can be repeated by adjusting the target thickness of the mineral wall as needed. Finally, both polymers used as templates were decomposed and removed by firing at 600-1000 ° C. for 4 hours at 0.5 ° C./min.

Example 2 Synthesis of Hierarchical Porous Biomaterial Using P123

In order to induce hexagonal nanopore structure, block copolymer Pluronic P123 ((polyethylene oxide) 20 (polypropyloxide) 70 (polyethylene oxide) 20) was used as a template.

First, except for dissolving P123 (2.28 g) in ethanol (18.1 ml) is the same as in Example 1.

FIG. 2 is an optical microscopy photograph of a porous biomaterial obtained by using a polyurethane sponge (left), a block copolymer and a polyurethane sponge according to an embodiment of the present invention. In the present invention, by using four polyurethane sponges having different pore sizes of 30 ppi, 45 ppi, 60 ppi, and 80 ppi ( left - A , B , C , and D , respectively), the sponge is immersed in a precursor solution four times and dried, and then fired. To obtain a three-dimensional porous biomaterial ( right - A , B , C , and D , respectively). As shown in FIG. 3 , the precursor solution is uniformly leaked in the polyurethane sponge, and the fired body reflects the pore size and structure of the polyurethane as it is.

Formation of the nano-sized pore structure was confirmed in the results of small angle X-ray diffraction measurement graph ( Fig. 3 ) and transmission electron micrograph ( Fig. 4 ).

3 is a graph showing small-angle X-ray diffraction (XRD) measurement results of porous biomaterials for the block copolymers F127 and P123 according to an embodiment of the present invention. As shown in FIG. 3 , since the biomaterial covering the polyurethane wall includes the block copolymer in the precursor solution, the regular pore structure of the nanosized is obtained during the firing process, and the pore structure is the structure of the block copolymer. Will reflect. In other words, if F127 is mixed, the pores of the cubic crystals will have the walls of the biomaterial, and if P123 is mixed, the pores of the hexagonal crystals will have the pores of the biomaterial walls.

4 is a transmission electron microscope (TEM) photograph and an optical microscope (bottom) photograph of a porous biomaterial for a block copolymer (F127 (left) and P123 (right)) according to an embodiment of the present invention.

In this experiment, it was found that the nanopores had better regularity than when F127 was mixed in the polyurethane ( FIG. 4 (left) ) and when P123 was leaked ( FIG. 4 (right) ).

5 is an example in which a synthesis method according to an embodiment of the present invention is compared with a conventional synthesis method. As shown in FIG. 5 , the conventional synthesis method synthesizes and calcinates ceramic powder, pulverizes, sifts it, mixes it with a solvent, forms a slurry, and then leaks and calcinates the polyurethane to remove the polyurethane, As a method of repeating the firing process, a long time and a process was required (Korean Patent No. 0331990). In addition, various additives such as crack inhibitors, dispersion stabilizers, and binders are required to make the slurry, and it is difficult to uniformly support the polyurethane in the slurry state, and various technologies such as preventing clogging and removing air are required. It became.

However, in this synthesis method, the sol solution for synthesizing the ceramic is coated on the polyurethane sponge as it is fired, so that the precursor solution is uniformly coated along the polyurethane sponge wall, and a three-dimensional pore structure having a desired size can be obtained by only one firing process.

Example 3 Synthesis of Hierarchical Porous Biomaterial Using Surfactant

In order to obtain a pore size of 2 to 3 nm, a surfactant, in particular CTAB, was used as a representative template.

First, CTAB (0.66 g) was added to distilled water (1037 ml) and ammonia water (26.6 ml) and stirred at 50 ° C. until the CTAB was completely dissolved, and then stirred again until the solution was cooled to room temperature. Tetraethyl orthosilicate (3 ml) was slowly mixed with this solution while stirring at a strong speed of 700 to 1500 rpm to obtain a precursor solution. Polyurethane sponge (pore size: 30 ppi) was cut into an appropriate size and ultrasonically cleaned in this precursor solution, and stirred at room temperature for 2 hours (the surface of the polyurethane sponge may be hydrophilically modified as necessary). The polyurethane sponge was taken out and dried in a constant temperature and humidity chamber at -15 to 80 ° C and 5 to 100 RH% for 1 hour, and then put back into the precursor solution and stirred slowly for 1 hour. The process of deposition and drying was repeated four times. If necessary, the process of deposition and drying can be repeated several times. After the drying process, both polymers used as templates were decomposed and removed by firing at 600 ° C./min at 600 ° C./1000° C. for 4 hours.

FIG. 6 is an optical microscope (A), a scanning electron microscope (SEM-B, C), and a transmission electron microscope (D) of a porous biomaterial using a surfactant and a polyurethane sponge according to an embodiment of the present invention. ) Photo. As shown in FIG. 6 , when the surfactant is used, it can be observed that a porous biomaterial having a hierarchical pore structure of nano size and macro size is synthesized. As shown in FIG . 6A , the silica precursor solution was uniformly applied to the polyurethane sponge, and a three-dimensional porous biomaterial reflecting the pore size (30 ppi) of the polyurethane sponge was obtained. B , C of Figure 6 can be seen that the porous biomaterial is composed of glass nanopowder of about 70 nm size. In addition, the glass nanopowder is a porous nanopowder having a two-dimensional hexagonal pore structure from the transmission electron micrograph of FIG. 6D . Therefore, it can be seen that a hierarchical porous biomaterial having two pores of nano size (2 to 3 nm) and macro size (200 to 500 μm) is manufactured by the synthesis method of the present invention.

As described above, in the present invention, unlike the conventional synthesis method requiring two or more firings, the hierarchical pore structure of the nano-macro size having the nanosized pores continuously connected with the macropores in one firing Biomaterials can be synthesized. In addition, since the synthesis method is simple and excellent in reproducibility and productivity and economical efficiency, in addition to bone fillers, restoratives and supports, for example, dental implant coating materials, anticancer agents, anti-inflammatory agents, hormones, contraceptive agents, non-smoking agents, and the like listed above. It is expected that the functions can be applied in various fields such as multifunctional materials, separators, ion exchange membranes, catalysts, filters, etc., in which these functions are combined.

Claims (20)

In the polyurethane polymer sponge having a macropore structure in the range of 1 to 1000 μm, a biomaterial in which calcium and phosphorus are uniformly dispersed in silicon and nanopores in the range of 1 to 100 nm are formed by a structure inducing agent. , A porous biomaterial having a nano-macro size hierarchical pore structure formed such that macropores in a range of 1 to 1000 μm and nanopores in a range of 1 to 100 nm are interconnected in a two-dimensional and three-dimensional hierarchical pore structure. The porous biomaterial of claim 1, wherein the nanoporous structure inducing agent is a cationic and anionic surfactant selected from CTAB or CTAC. The porous biomaterial of claim 1, wherein the nanoporous structure inducing agent is a block copolymer of polyethylene oxide-polypropylene oxide-polyethylene oxide. The nano-macro size hierarchical structure according to claim 3, wherein the structure inducing agent is a pluronic or tetronic block copolymer selected from the group consisting of F127, F108, F98, F88, P123, P105, and P104. Porous biomaterial having a pore structure. (a) dissolving a block copolymer of polyethylene oxide and polypropylene oxide in an organic solvent containing alcohol to synthesize a block copolymer template solution; (b) mixing the silicon compound, the calcium compound and the phosphorus compound to synthesize a biomaterial solution; (c) adding the biomaterial solution to the block copolymer template solution to obtain a precursor solution; (d) depositing and drying a polyurethane polymer sponge in the precursor solution; And (e) calcining the dried product obtained in (d) to remove residual organic material and the template Method of synthesizing a porous biomaterial having a hierarchical pore structure of nano-macro size. The nano-macro size according to claim 5, wherein the block copolymer template is a pluronic or tetronic copolymer selected from the group consisting of F127, F108, F98, F88, P123, P105 and P104. A method for synthesizing porous biomaterials having a hierarchical pore structure. According to claim 5, In the step (b) silicon, calcium and phosphorus is a porous bio-structure having a nano-macro size hierarchical pore structure is contained in an element ratio of 50 ~ 80: 18 ~ 45: 2 ~ 10 Synthesis of materials. The method according to claim 5, wherein in step (c) the block copolymer template solution is added to the biomaterial solution of 30 to 50% by mass of the porous biomaterial having a nano-macro sized hierarchical pore structure Synthesis method. According to claim 5, The step (c) is a porous biomaterial having a nano-macro sized hierarchical pore structure comprising the step of mixing and stirring for 2 to 72 hours at 700 ~ 1500 rpm and 30 ~ 80 ℃ Method of synthesis. The method according to claim 5, wherein the polyurethane polymer sponge of step (d) is treated with a NaOH aqueous solution of the polyurethane polymer sponge surface-modified polyurethane polymer sponge hydrophilic, and the surface-modified polyurethane polymer sponge is washed with distilled water Synthesis method of porous biomaterial having a hierarchical pore structure of nano-macro size. The method of claim 5, wherein the drying in step (d) is performed at a temperature in the range of −15 to 80 ° C. and 5 to 100 RH%. . The method of claim 5, wherein the deposition and drying of step (d) are performed 1 to 10 times. The method of claim 5, wherein the firing in the step (e) comprises the step of densifying and slow cooling the skeleton by maintaining the dried product for 2 to 6 hours in the range of 600 to 1000 ° C at a temperature increase rate of 0.2 to 2 ° C / min. Synthesis method of porous biomaterial having hierarchical pore structure of phosphorus nano-macro size. (A) dissolving the surfactant in an organic solvent containing ammonia water to synthesize a surfactant template solution; (b) mixing a silicon compound with the surfactant template solution to obtain a sol precursor solution; (c) depositing and drying the polyurethane polymer sponge in the sol solution obtained in step (b); And (d) calcining the dried product obtained in step (c) to remove residual organics and the template Method of synthesizing a porous biomaterial having a hierarchical pore structure of nano-macro size. 15. The method of claim 14, wherein the surfactant is a cationic and anionic surfactant selected from CTAB or CTAC. 15. The method of claim 14, wherein step (b) is a porous biomaterial having a nano-macro sized hierarchical pore structure comprising the step of mixing and stirring for 2 to 72 hours at 700 ~ 1500 rpm and 30 ~ 80 ℃ Method of synthesis. 15. The method according to claim 14, wherein the polyurethane polymer sponge of step (c) is treated with a NaOH aqueous solution of the polyurethane polymer sponge surface-modified polyurethane polymer sponge hydrophilic, and the surface-modified polyurethane polymer sponge is washed with distilled water Synthesis method of porous biomaterial having a hierarchical pore structure of nano-macro size. 15. The method of claim 14, wherein the drying in step (c) is carried out at a temperature in the range of -15 to 80 ° C and 5 to 100 RH%. . 15. The method of claim 14, wherein the deposition and drying of step (c) are repeated 1 to 10 times. 15. The method according to claim 14, wherein the firing in step (d) comprises the steps of densifying and slow cooling the skeleton by maintaining the dried product at a temperature rising rate of 0.2 to 2 ° C / min for 2 to 6 hours in the range of 600 to 1000 ° C. A method for synthesizing a porous biomaterial having a hierarchical pore structure of phosphorus nano-macro size.

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