KR20090058138A - Bio-degradable triple pore ceramic-polymer scaffold and preparation method thereof - Google Patents

Abstract

A porous ceramic-polymer support and a preparation method for the same are provided, which additionally create the pore of the micro-size by introducing a particle-leaching method. A preparation method of porous ceramic-polymer support comprises: a step of synthesizing the block copolymer template solution by dissolving the block copolymer of the polypropylene oxide and polyethylene oxide in the organic solvent including the alcohol; a step of synthesizing the biodegradation property ceramic solution by mixing the calcium compound and phosphorus compound; a step of obtaining the precursor solution by adding the biodegradation property ceramics solution to the block copolymer template solution; a step of obtaining the porous ceramic material by drying and plasticizing the precursor solution; a step of pulverizing the porous ceramic material in the size of the sub-mark; a step of obtaining the paste by mixing a biodegradable polymer and pulverized porous ceramic material; a step of forming the air bubble of the giant size; and a step of leaching the particle.

Description

Biodegradable triple pore ceramic-polymer support and preparation method thereof Bio-degradable triple pore ceramic-polymer scaffold and preparation method

The present invention relates to a biodegradable triple-porous ceramic-polymer support and a method of manufacturing the same, by introducing a new particle leaching method to a ceramic-polymer support having a double pore produced by a combination of a laminate molding method and a polymer template method. The present invention relates to a porous ceramic-polymer support having a triple pore by additionally generating pores thereof and a method of manufacturing the same.

Tissue engineering is a multidisciplinary field of disciplines aimed at developing biological products that use the principles of biosciences and engineering to restore, maintain, or enhance the function of tissues. A typical method is to artificially form tissues by separating and culturing cells from tissues to be regenerated and inoculating them into appropriate biomaterials and amplifying the cultures. This procedure requires proper cell support to attach cells to props and transfer them to the necessary sites, and to make new tissues that can function mechanically and function as a three-dimensional structure for tissue growth. These scaffolds must have the appropriate microstructures to allow cells to multiply and create unique substrates, and have many pores interconnected three-dimensionally on the surface so that cells can grow inwards through these pores, As the organization grows, it should not be blocked. It should also be a biodegradable material that is nontoxic and can be completely degraded in vivo after termination of function as a support.

In general, many porous polymers are used as the support, but since the polymer is difficult to obtain the appropriate mechanical strength required for the support, many developments of the three-dimensional porous support using bioceramic are being performed for reasons of securing mechanical strength and bone affinity. However, ceramics also have the disadvantage of fragile, and in recent years, a method of compensating for mutual disadvantages by manufacturing a composite of a biodegradable polymer and a bioceramic has also been proposed.

Synthesis of three-dimensional pore structure includes particle leaching, gas foaming, fiber meshes, phase separation, emulsion freeze drying, etc. However, the above synthesis method is not easy to control the size of the pores, the surface area and porosity of the obtained support is relatively low, there is a problem that the pore clogging phenomenon of the surface of the support is caused because the open structure is not well formed between the pores. Recently, a rapid prototyping method has been proposed for the creation of a scaffold with the aid of a computer, and this method solves the above problems and increases the pore size (giant pores) required for cell growth. 1000μm) is effective to produce three-dimensional.

On the other hand, the support to date has mostly controlled the pore size in the giant size region, and in recent years, it is expected to increase the specific surface area and porosity, improve cell adhesion, cell proliferation, differentiation, and prevent cell death. In the nano, macro, and giant pore regions, a manufacturing method for controlling the size and shape of pores such as double pores (Korean Patent No. 751504) or triple pores (Korean Patent Application No. 2006-103013) has been proposed. In particular, in order to increase the bioactivity and biodegradability, and anti-cancer drugs, such as anti-inflammatory drugs can be expected to study the effect of introducing pores of the nano-size region to the support. Korean Patent Application No. 2006-105013 describes a method for synthesizing a ceramic support having giant, macro and nano-sized pores or a ceramic-polymer support having giant and nano-sized pores using rapid prototyping and polymer template methods. The significance of the support having pores is shown. However, the mechanical properties of the porous ceramic support are insufficient to be used as a support. On the other hand, in the case of ceramic-polymer support, the improvement of mechanical strength is recognized, but includes only giant and nano-sized pores. There is a problem that the pores of the macro size required as the movement path of the discharge and the like are not included.

Accordingly, the inventors have found out a paste in which water-soluble particles are dispersed in a nanoporous ceramic-polymer composite in a gel state using a multilayer molding machine and a three-dimensional ceramic polymer support having a triple pore, and a method of manufacturing the same. It was.

It is an object of the present invention to provide a biodegradable triple pore ceramic-polymer support.

Another object of the present invention is to provide a method for producing a biodegradable triple pore ceramic-polymer support.

In order to achieve the above object, the present invention is a biodegradable polymer in which the biodegradable ceramic powder in which calcium and phosphorus are uniformly dispersed in silicon is uniformly distributed, the giant size of 100 ~ 1000 ㎛ range, 1 ~ 100 ㎛ range The present invention provides a biodegradable triple pore ceramic-polymer support in which macropores of and nanopores in the range of 1 to 100 nm are three-dimensionally interconnected open pores.

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) mixing the silicon compound, the calcium compound and the phosphorus compound to synthesize a biodegradable ceramic solution; (c) adding the biodegradable ceramic solution to the block copolymer template solution to obtain a precursor solution; (d) drying and firing the precursor solution to obtain a porous ceramic material; (e) grinding the porous ceramic material into sub-macro sizes; (f) uniformly mixing the pulverized porous ceramic material with leachable particles ground to a sub-macro size, and then mixing the biodegradable polymer to obtain a paste; (g) inserting the paste into a three-axis molding machine and spraying to form pores of a giant size; And (h) provides a method of producing a biodegradable triple-porous ceramic-polymer support comprising the step of leaching the particles by repeating the steps of drying, dipping and washing the porous support formed above.

According to the present invention, by introducing a new particle leaching method into a ceramic-polymer support having double pores produced by a combination of a laminate molding method and a polymer template method, the support additionally generates macro-sized pores. By including all nano-sized pores, the mechanical strength was complemented while maintaining efficient cell proliferation and differentiation, preventing cell necrosis, and selective drug release. These properties are advantageous for cell adhesion, division, proliferation, migration and differentiation. By providing conditions, it can be usefully used in various fields besides bone filler, restorative material, and support. In addition, the support shows high elasticity in a dry or wet state and can be applied as a support for minimal invasive surgery.

Hereinafter, the present invention will be described in detail.

The present invention provides a biodegradable polymer in which calcium and phosphorus are uniformly dispersed in silicon, and a biodegradable polymer having a giant size in the range of 100 to 1000 μm, a macro size in the range of 1 to 100 μm, and 1 to 100. The nanoscale pores in the nm range provide biodegradable triple pore ceramic-polymer supports in which open pores are formed three-dimensionally interconnected.

The pores of the giant size are formed by a triaxial molding machine, the pores of the macro size are formed by the particle leaching method, and the nano-sized pores are used for inducing the pores of the nano-sized block copolymer of polyethylene oxide and polypropylene oxide. It is preferable to form using a template.

The three-dimensional interconnected open pore structure is formed by an organic template forming a self-organization such as a block copolymer, and nano-size open pores form a regular structure such as two-dimensional or three-dimensional hexagonal or cubic crystal. Refers to shapes that are interconnected. The giant pore structure of the porous ceramic material also requires a shape in which pores are connected in a three-dimensional direction (x, y, z-axis direction) in order to be used as a support of a cell. The macro pore structure refers to pores generated by adding and mixing particles to a biodegradable ceramic and a biodegradable polymer paste, and then removing the particles, thereby ensuring all mechanical strengths and having all the efficiencies of the triple pores. Will be. As said particle | grain, sodium chloride, ammonium bicarbonate, sodium bicarbonate, saccharin, etc. are preferable, and sodium chloride is more preferable.

The biodegradable ceramics, including calcium and phosphorus such as bioactive glass, low crystalline apatite, tricalcium phosphate (TCP), induce the production of apatite, a bone-like component, and in vivo degradation of the support. Although ceramics can be used, it is preferable to use bioactive glass.

The biodegradable polymers include polycaprolactone (Poly (ε-caprolactone); PCL), polylactic acid (PLA), polylactic acid-glycol, which can be applied as artificial skin grafts or surgical sutures. Acid copolymers (PLGA), polyamino acids and polyglycolic acid (Poly (glycolic acid); PG) and the like can be used, with PCL being preferred. The biodegradable polymer is decomposed into lactic acid and removed through metabolism at all, especially when implanted in vivo as a material suitable for treating fractures requiring long-term treatment.

In addition, the present invention comprises the steps of dissolving the block copolymer of polyethylene oxide and polypropylene oxide in an organic solvent containing alcohol to synthesize a block copolymer template solution (step (a)); Mixing a silicon compound, a calcium compound and a phosphorus compound to synthesize a biodegradable ceramic solution (step (b)); Adding the biodegradable ceramic solution to the block copolymer template solution to obtain a precursor solution (step (c)); Drying and firing the precursor solution to obtain a porous ceramic material (step (d)); Grinding the porous ceramic material into submarks in size (step (e)); Uniformly mixing the pulverized porous ceramic material with the pulverized particles to a submark size and then mixing the biodegradable polymer to obtain a paste (step (f)); Inserting the paste of step 6 into a three-axis molding machine and spraying to form pores of a giant size (step (g)); And it provides a method for producing a biodegradable tri-porous ceramic-polymer support comprising the step of leaching particles (step (h)) by repeating the process of drying, dipping and washing the formed porous support several times.

Hereinafter, the manufacturing method according to the present invention will be described in more detail step by step.

Step (a) according to the present invention is a step of synthesizing a block copolymer template solution by dissolving a block copolymer of polyethylene oxide and polypropylene oxide in an organic solvent containing alcohol, wherein the block copolymer template is a polyethylene oxide- A poloxamer having a structure of polypropylene oxide-polyethylene oxide may be used, and the poloxamer used may be a Pluronic or Tetronic polymer having a hydrophilic group and a hydrophobic group. . Among these, 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 (poly Propylene 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), and hydrophilic polymers such as Pluronic, Tetronic, Reverse Pluronic, or Reverse Tetronic, with a polyethylene / polypropylene ratio of 0.1 to 0.8. Block copolymers composed of blocks and hydrophobic polymer blocks can be used. The pore structure is determined according to the type of block copolymer used in the present invention. When F127 is used, it is easy to form a three-dimensional cubic structure, and when P123 is used as a template, a two-dimensional hexagonal (hexagonal) is used. ) Is easy to achieve the structure.

Here, the nano-size template for covalent sharing may include CTAB (cetyltrimethylammoniumbromide) or CTAC (cetyltrimethylammoniumchloride) or other carbon atoms, such as C ₂ to C ₄₀ dodecyl ammonium bromide, sodium dodecyl sulfate, and polydi- ethane, in addition to the block copolymer. Surfactants such as allyldimethylammonium chloride, stearylammonium bromide, and stearylmethylammonium bromide can be used.

Although the said alcohol solvent is not specifically limited, What has a C1-C25 alkyl chain can be used. 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 a biodegradable ceramic solution by mixing a silicon compound, calcium compound and phosphorus compound, a method of mixing each starting solution at a predetermined interval, or adding an acid or alkaline solution It is possible to uniformly disperse calcium and phosphorus in silica, and evenly disperse calcium or phosphorus in silica to suppress crystallization generated during mixing.

The silicon compound, the calcium compound and the phosphorus compound have an element ratio of Si: Ca: P of 50 to 80:18 to 45: 2 to 10, preferably 75Si: 21Ca: 4P, 55Si: 41Ca: 4P. By mixing, biodegradable ceramic solutions can be synthesized. It is because a stable cubic nanopore structure is formed in the above-mentioned range. Especially, it is preferable that the said calcium compound is contained in 10-40 mass% with respect to the total amount of the said silicon compound, the said calcium compound, and the said phosphorus compound. In the above concentration range, the formation of the cubic nano-pore structure is confirmed, but the porosity is higher but the regular structure of the pores is deteriorated at 40 mass% or more.

The biodegradable ceramics include calcium and phosphorus, such as bioactive glass, low crystalline apatite and tricalcium phosphate (TCP), to induce the production of apatite, which is a bone-like component, and to induce degradation of the support in vivo. Ceramics can be used, and preferably bioactive glass can be used.

In the present invention, as the silicon compound, tetraethylolsosilicate, 3-mercaptopropyltrimethoxysilane, 5,6-epoxyhexyltriethoxysilane, and the like may be used, and tetraethylolsosilicate is preferably used. The calcium compound may be used calcium nitrate tetrahydrate, calcium nitrate, calcium chloride and the like, it is preferable to use calcium nitrate tetrahydrate. As the phosphorus compound, triethyl phosphate, sodium phosphate, ammonium phosphate dibeix and the like can be used, and triethyl phosphate is preferably used.

Next, step (c) according to the present invention is a step of obtaining a precursor solution by adding the biodegradable ceramic solution of step (b) to the block copolymer template solution of step (a), 750 ~ 1500 rpm and 30 ~ It may include the step of stirring the mixed solution for 2 to 72 hours at 80 ℃.

In the mixing process of step (c), the block copolymer template solution and the biodegradable ceramic solution may be used by mixing at 30-50 mass%.

Next, step (d) according to the present invention is a step of obtaining a porous ceramic material by drying and firing the precursor solution of step (c), wherein the firing is preferably performed at a temperature of 500 ° C. at a temperature rising rate of 0.2 to 2 ° C./min. Maintaining at a temperature range of 800 ℃ for 2-6 hours to densify the skeleton and slow cooling, in this case, when the firing temperature and time exceeds the range, calcium or phosphorus oxide crystals are non-uniformly generated and nano-pores Problems can arise that cause the structure to collapse.

In addition, the drying may be preferably carried out at a temperature of -15 ~ 80 ℃ and 5 ~ 100 RH%.

Next, step (e) according to the present invention is the step of crushing the porous ceramic material of step (d) to a sub-mark size, for example, the porous ceramic material in the range of 1 ~ 100 ㎛ through ball milling (ball-milling) It is preferred to be ground.

Next, in step (f) according to the present invention, the porous ceramic material pulverized in step (e) is uniformly mixed with the leach particles pulverized into submarks, and then the mixture is mixed with a biodegradable polymer to prepare a paste. In the step of obtaining, the biodegradable polymer is a polycaprolactone (poly (ε-caprolactone)), polylactic acid (poly (lactic acid)), polylactic acid-that can be applied as an artificial skin graft material or surgical sutures Glycolic acid copolymer (PLGA), polyamino acid or polyglycolic acid (Poly (glycolic acid)) and the like can be used, it is preferable to use polycaprolactone.

The biodegradable polymer is decomposed into lactic acid and removed through metabolism at all, especially when implanted in vivo as a material suitable for treating fractures requiring long-term treatment.

As the leaching particles, sodium chloride, ammonium bicarbonate, sodium bicarbonate, ice, saccharin, and the like may be used, and sodium chloride may be preferably used.

Preferably, the porous ceramic material and the biodegradable polymer of step (f) are mixed at a mass ratio of 20 to 80:80 to 20, and the leaching particles are based on the sum of the weights of the porous ceramic material and the biodegradable polymer. It is preferable that the amount of 0.5 to 2 times be mixed.

Next, step (g) according to the present invention is a step of forming the pores of the giant size by inserting the paste of step (f) into the three-axis molding machine, and spraying, the direction of the ejection particle size and the X-axis, Y-axis direction of the three-axis molding machine And two- or three-dimensional shapes can be designed easily by controlling the paste ejection speed. At this time, if necessary to maintain the shape of the paste extruded during the air flow 20 ~ 40 ℃ while cooling the substrate to a temperature of -5 ~ 10 ℃ can promote the solidification of the PCL.

Finally, step (h) according to the present invention is a step of leaching the particles by repeating the process of drying, dipping and washing the porous support formed in step (g) several times, preferably in the case of the drying 5 ~ 25 ℃ At a temperature of 24 to 48 hours, the immersion of the porous support formed in the step (f) in distilled water or bio-analogous liquid for 4 to 24 hours, it is preferable to wash after.

In the case of the washing, the support may be repeatedly stressed to remove the remaining particles. In addition, in the case of a sample that is easy to elute calcium or phosphorus in an aqueous solution, such as a biodegradable ceramic, in order to prevent the release and to generate apatite to improve the mechanical strength and biocompatibility, in some cases, a biosimilar liquid is used instead of distilled water. The particles can be leached. After the particle leaching, vacuum drying can be used to remove the moisture and the remaining solvent inside the support.

Hereinafter, the present invention will be described in more detail with reference to Examples and the accompanying drawings. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

The synthesis method of the present invention was schematically shown as in Fig.

After synthesizing the nano-porous ceramic having nano-sized pores, and fractionated into macro size, the ceramic is mixed with the particle sized to the macro size, and then the mixture is stirred with the biodegradable polymer paste. After the stirring, a ceramic-polymer porous material having a triple pore structure can be obtained by forming a computer-controlled three-dimensional shape through a multilayer molding machine and then removing the remaining solvent.

< Example  1> Ceramic-Polymer with Triple Pore Structure Porous material

Pluronic F127 (polyethylene oxide) 100 (polypropylene oxide) 65 (polyethylene oxide) 100) to induce cubic three-dimensional nanoporous structure, and hexagonal nanoporous structure to induce Pluronic P123 ((polyethylene oxide) 20 (polypropylene oxide) 70 (polyethylene oxide) 20) was used as the block copolymer template. First, F127 (2.88 g) was mixed with ethanol (18.1 ml) and stirred for 0.5 to 1 hour until completely dissolved at 40 ° C (solution A). At the same time, tetraethylolsosilicate (TEOS, 6 ml) and calcium titrate tetrahydrate (1.36 g), which are raw materials of bioactive glass, were slowly mixed and triethyl phosphate (0.26 ml) was mixed when a uniform solution was produced. Next, 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 thereto, and the mixture was 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 2-4 hours at a strong speed of 700-1500 rpm.

The precursor solution thus obtained was placed in an appropriate amount in a hydrophobic container (for example, a polystyrene container), and the solution was evaporated and dried while being kept in a constant temperature and humidity chamber at -15 to 80 ° C for 5 to 100 RH% for 24 to 48 hours. In addition, when the precursor solution was coated on a constant substrate, a thin porous ceramic material was also obtained. This was heated at a rate of 1 ℃ / min and calcined at 500 ~ 1000 ℃ for 4 hours to remove F127 used as a template to obtain a porous bioactive glass having a three-dimensional regular structure of pores in the nano-size.

The obtained porous bioactive glass was fractionated to 25 micrometers or less, separated from the NaCl, dried and pulverized to 25 micrometers or more and 35 micrometers or smaller. After uniformly stirring a predetermined amount of nanoporous bioactive glass and NaCl, the bioactive glass powder was mixed with polycaprolactone (PCL) paste, a biodegradable polymer dissolved in chloroform, taking care not to entangle NaCl. Nanoporous bioactive glass and PCL were mixed at a weight ratio of 2: 8 to 8: 2, and NaCl was mixed in an amount of 0.5 to 2 times the total weight of the bioactive glass and PCL. The paste made of nanoporous bioglass / NaCl / PCL was put in a three-axis molding machine to control the spacing and shape of the X-axis, the Y-axis, and the Z-axis to create a giant pore having a desired size and shape. At this time, in order to maintain the shape, as necessary, during the extrusion of the paste, air of about 20 to 40 ° C. was injected to remove chloroform and the substrate was cooled to a certain temperature to promote hardening of the PCL. After drying at 5-25 ° C. for 1 day, the steps of immersing and washing NaCl by dipping in distilled water were repeated several times. In this step, the support was repeatedly stressed to remove residual NaCldmf. In addition, in the case of a sample which is easily eluted with calcium or phosphorus in an aqueous solution, such as bioactive glass, a simulated body fluid may be selectively used to suppress the release and to generate apatite to improve mechanical strength and biocompatibility. The salt particles were leached using distilled water metabolism. After the leaching of the salt particles, water and residual solvent in the support were removed through a vacuum drying step.

Figure 2 shows a bioactive glass-biodegradable polymer support showing a triple pore structure according to an embodiment of the present invention. Figure 2 (c) is a reproduction of the computer-designed three-dimensional model and the pores of the giant size, the three-dimensional shape and size can be freely produced by the design of the computer, the shape and size of the giant pores paste It can be controlled according to the distance between pillars squeezed in a column shape or a method of stacking pillars. Also pillar to create a giant pore can be confirmed through a 10 - 2 that includes the macro pore size of 50 ㎛ (c) and the picture as an expanded view of a portion of the column of Figure 2 (b). The size of the macropores can be controlled according to the size of the leaching particles used, and the pore area can be increased by increasing the ratio of the leaching particles to the ceramic-polymer paste. The pillars forming the giant pores include macro-sized bioactive glass, and the bioactive glass is composed of nanopores having a size of 5 to 7 nm by using a nanostructure inducer such as a block copolymer as a template . This can be seen from the transmission micrograph of (a).

Figure 3 shows the results of evaluating the compression ratio of the bioactive glass-biodegradable polymer support showing a triple pore structure according to an embodiment of the present invention. FIG. 3 (a) shows a double-porous organic-inorganic composite support having 0 NaCl, that is, 60 mass% of bioactive glass added to PCL, and at least 10 times as compared with a ceramic support including a triple pore structure. It can be seen that the mechanical strength is enhanced. In the case of the organic-inorganic composite support ( Fig. 3 (b)) having a triple pore structure by adding 75% NaCl to the weight of the bioactive glass and PCL to the organic-inorganic composite support to remove NaCl with distilled water It can be seen that the strength is lower than that of the organic-inorganic composite support, but still exhibits better mechanical properties than the ceramic support having the triple pore structure. According to FIG. 3 , the compression ratio tends to decrease as the amount of NaCl added increases. This increases the porosity of the macro-sized pores in the pillars of the support as the macroporosity increases, resulting in a nonuniform distribution of force on the compressive stress. Because. However, as the macropores increase, the compressibility decreases, but it does not break like the ceramic support but has elasticity like a sponge, which can be seen from FIG. 4 .

Figure 4 is the result of the sample obtained by adding NaCl 100% to the weight of the bioactive glass and PCL through which it can be seen that the result has a high elasticity. The support of FIG. 4 has high elasticity even in a dry state or a wet state and is superior to a dry state. By using the elasticity, a large support may be put in a small ablation site and may be usefully used for minimally invasive surgery for inducing rapid recovery of the surgical site.

FIG. 5 shows whether the formation of apatite crystals containing bio-bones and similar components after immersion in analog fluid to evaluate the bioactivity of the bioactive glass-biodegradable polymer support showing the triple pore structure obtained in the Examples of the present invention. Observed. As confirmed through (d) of FIG. 5 , in the case of the three-dimensional support made of the biodegradable polymer PCL alone, the formation of crystals recognized as apatite was not confirmed even after 24 hours deposition. On the other hand, in FIG. 5 According to (a) to (c) of FIG. 5 , it can be seen that apatite is rapidly formed in the bioactive glass-biodegradable polymer support having a triple pore structure. In general, bioactive glass has high bioactivity when manufactured by the sol-gel method, but it takes at least 3 days to produce apatite, whereas in the case of the support of the present invention, the nanoporous bioactive glass is used as the ratio with the biological fluid. Since the surface area was increased to increase the bioactivity of the glass, it was found that the apatite crystals formed about 1 hour after deposition even in the composite obtained by mixing with PCL without bioactivity, and the amount increased after 4 hours, After 24 hours of deposition, it can be seen that the apatite crystals cover much of the support. Through this, it can be seen that the bioactive glass-biodegradable polymer support showing the triple pore structure of the present invention exhibits high bioactivity leading to rapid bone formation and can be usefully used as a support in tissue engineering for bone formation. have. FIG. 6 is a result of component analysis of the crystals observed in FIG. 5 , and it can be seen that the crystals formed are apatite-like crystals.

1 is a schematic diagram of a ceramic-polymer porous material synthesis method having a triple pore structure,

FIG. 2 is a scanning electron micrograph of a ceramic-biodegradable polymeric porous support having a triple pore structure ((a): giant pores formed by rapid prototyping, (b): macro pores formed by particle leaching) and transmission electron microscope Photograph ((c): nano-pores formed by the polymer template method),

3 is a macropore by changing the weight percentage ((a): 0 NaCl, (b): 75 NaCl, (c): 150 NaCl, (d) 300 NaCl) ratio of NaCl to the combined weight of ceramic and polymer It is a graph showing the change of the condensation rate according to the formation and the change of the condensation rate of the polymer support (e) and the ceramic support (f) obtained by the particle leaching method,

4 is a photograph showing the elasticity of the ceramic-biodegradable polymeric porous support having a triple pore structure,

FIG. 5 shows bioactivity according to time after deposition of analog liquid of a ceramic-biodegradable polymeric porous support having a triple pore structure ((a): 0 hour, (b): 4 hour, (c): 24 hour) An optical micrograph and an optical micrograph (d) showing bioactivity after immersing the biodegradable polymer support in an analogous solution for 24 hours,

FIG. 6 is a graph of a ceramic-biodegradable polymer porous support having a triple pore structure after deposition in an analogous liquid, and analyzing the composition of crystals formed on the support by using an energy dispersive X-ray spectrometer.

Claims (21)

Biodegradable polymers in which calcium and phosphorus are uniformly dispersed in silicon are biodegradable polymers having a giant size in the range of 100 to 1000 μm, a macro size in the range of 1 to 100 μm and a range of 1 to 100 nm. Open pores in which nanosized pores are interconnected three-dimensionally are formed, and the pores of the giant size are formed by a three-axis molding machine, and the pores of the macrosize are formed by leaching particles. A biodegradable triple pore ceramic-polymer support having elasticity in dry and wet conditions formed by using block copolymers of polyethylene oxide and polypropylene oxide as nano-sized pore guidance templates. The biodegradable triple pore ceramic-polymer support of claim 1, wherein the biodegradable ceramic is selected from the group consisting of bioactive glass, low crystalline apatite and tricalcium phosphate (TCP). The biodegradable triple pore ceramic-polymer support of claim 1, wherein the particles are selected from the group consisting of sodium chloride, ammonium bicarbonate, sodium bicarbonate, ice and saccharin. The biodegradable triple pore ceramic-polymer support of claim 1, wherein the biodegradable polymer is selected from the group consisting of polycaprolactone, polylactic acid, polylactic acid-glycolic acid copolymer, polyamino acid and polyglycolic acid. The biodegradable triple pore ceramic-polymer support of claim 1, wherein the biodegradable polymer is polycaprolactone. (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 a silicon compound, a calcium compound and a phosphorus compound to synthesize a biodegradable ceramic solution (step 2); (c) adding the biodegradable ceramic solution to the block copolymer template solution to obtain a precursor solution; (d) drying and firing the precursor solution to obtain a porous ceramic material; (e) milling the porous ceramic material into sub-macro sizes; (f) uniformly mixing the ground porous ceramic material with the leached particles ground to a sub-macro size and then mixing the biodegradable polymer to obtain a paste; (g) inserting the paste into a three-axis molding machine and spraying to form pores of a giant size; And (H) a method of producing a biodegradable tri-porous ceramic-polymer support comprising the step of leaching the particles by repeating the process of drying, dipping and washing the formed porous support several times. The method according to claim 6, wherein the block copolymer of polyethylene oxide and polypropylene oxide of step (a) is Ffluoro, F127, F108, F98, F88, P123, P105, P104, and polyethylene / polypropylene ratio of 0.1 ~ 0.8 A method for producing a biodegradable triple pore ceramic-polymer support, characterized in that at least one selected from the group consisting of nicks, tetronics, reverse pluronics, and reverse tetronics. The biodegradable triple pore ceramic according to claim 6, wherein the biodegradable ceramic solution of step (b) contains silicon, calcium and phosphorus at an element ratio of 50 to 80:18 to 45: 2 to 10. Method for producing a polymer support. The method according to claim 6, wherein the biodegradable ceramic of step (b) is selected from the group consisting of bioactive glass, low crystalline apatite and tricalcium phosphate. The method of claim 6, wherein the block copolymer template solution of step (c) and the biodegradable ceramic solution are mixed at 30 to 50 mass%. The method according to claim 6, wherein the step (c) is a method of producing a biodegradable triple-porous ceramic-polymer support, characterized in that the mixing and stirring for 2 to 72 hours at 30 ~ 80 ℃ at 750 ~ 1500 rpm. The method of claim 6, wherein the drying of the step (d) is carried out at a temperature of -15 ~ 80 ℃ and 5 ~ 100 RH%. The method according to claim 6, wherein the firing of step (d) is characterized in that the dried material is maintained at a temperature range of 500 ~ 800 ℃ for 2 to 6 hours at a temperature increase rate of 0.2 ~ 2 ℃ / min to densify the skeleton and slow cooling Method of producing a biodegradable triple pore ceramic-polymer support. The method of claim 6, wherein the particles of step (f) are selected from the group consisting of sodium chloride, ammonium bicarbonate, sodium bicarbonate, ice and saccharin. The biodegradable triple pore of claim 6, wherein the biodegradable polymer of step (f) is selected from the group consisting of polycaprolactone, polylactic acid, polylactic acid-glycolic acid copolymer, polyamino acid and polyglycolic acid. Method for producing a ceramic-polymer support. The method of claim 6, wherein the biodegradable polymer of step (f) is polycaprolactone. The method of claim 6, wherein the porous ceramic material and the biodegradable polymer of step (f) are mixed at a ratio of 20% to 80% by mass to 80% to 20% by mass. . The biodegradable triple pore ceramic-polymer support according to claim 6, wherein the leaching particles of step (f) are mixed in an amount of 0.5 to 2 times the total weight of the porous ceramic material and the biodegradable polymer. Manufacturing method. The method of claim 6, wherein the step (g) flows 20-40 ° C. during paste extrusion to maintain the shape of the formed giant-sized pores and simultaneously cools the substrate to a temperature of −5-10 ° C. to solidify the PCL. Method for producing a biodegradable triple pore ceramic-polymer support further comprising the step of promoting. The method according to claim 6, wherein the step (h) is dried for 24 to 48 hours at 5 ~ 25 ℃, immersed in distilled water or bio-analogue liquid for 4 to 24 hours to leach the salt, characterized in that the biodegradable Method for preparing tri-porous ceramic-polymer support. The method of claim 6, wherein the stress is repeatedly applied to remove the leach particles remaining in the formed porous support.

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