KR101230704B1 - Manufacturing method and apparatus for porous calcium phosphate scaffolds - Google Patents

Abstract

The present invention relates to a method for producing a porous calcium phosphate synthetic bone scaffold for reconstruction of the musculoskeletal system for dental and orthopedic surgery, wherein 20 to 60% by weight of the total paste weight is added to 30 to 70% by weight of distilled water. Dispersion, in the case of non-aqueous, dispersed in 30 to 70% by weight alcohol, to prepare a calcium phosphate paste of the aqueous or non-aqueous composition, impregnated and coated with a paste prepared in a polyurethane sponge, and dried at 1000 ~ 1350 ℃ Heat treatment produces a calcium phosphate scaffold.

Description

Calcium phosphate scaffold manufacturing apparatus and manufacturing method {Manufacturing method and apparatus for porous calcium phosphate scaffolds}

The present invention provides a method for producing a porous calcium phosphate synthetic bone support (hereinafter referred to as 'scaffold') connected to the pores by preparing a calcium phosphate paste and coating it on a polyurethane sponge and heat treatment at 1000 ~ 1350 ℃ It is about.

Currently, dental and orthopedic scaffolds are used not only as simple bone marrow restorations, but also in the field of tissue engineering in which stem cells of patients are attached to scaffolds and implanted into bone injury sites.

These scaffolds are used in the form of powders and porous blocks. When used in the form of double porous blocks, a pore size of at least 100 μm or more is required for blood vessels to grow into pores, and the pores are connected to each other. The form is reported to be advantageous.

However, conventional scaffolds use many methods such that the remaining pores remain after heat treatment after pressure molding after mixing the components volatile in the heat treatment process with calcium phosphate powder or paste as in the Republic of Korea Patent Publication No. 88-000066 There was a disadvantage in that a block in the form of pulmonary pores was obtained, and thus, the block in the form of pulmonary pores was not easy to grow blood vessels and attach cells.

As a technique to solve this problem, there is a method of coating the calcium phosphate paste on the polyurethane sponge and heat treatment, this sponge coating method can adjust the pore size of the final scaffold to the pore size of the starting sponge, The pore connection properties can be obtained as it is, thus inducing the growth of blood vessels in the human body and providing a very easy structure for attaching the stem cells of the patient to the inside of the scaffold.

However, when manufacturing a scaffold using a polyurethane sponge at present, as shown in Korean Patent No. 10-0401941, the sponge is completely impregnated into the paste so that the paste is excessively coated on the sponge, and then passed through a plurality of rollers. Rotate with a centrifugal separator to remove excess paste, but impregnation alone does not penetrate the calcium phosphate paste into the sponge sufficiently, the paste agglomerates at the edges of the sponge after rolling, or the center and edges are uneven. There is a disadvantage that the coating or pores are clogged.

Moreover, most currently attempted calcium phosphate pastes are prepared in an aqueous composition, which is easy for non-degradable materials such as hydroxyapatite (hereinafter referred to as 'HA'), but tricalcium phosphate (hereinafter referred to as 'TCP'). Decomposable calcium phosphate, such as biphasic calcium phosphate (hereinafter referred to as 'BCP'), is eluted from the surface of the powder particles during the preparation of the aqueous paste, so that the particles agglomerate to form coarse aggregated particles. A stable paste cannot be prepared.

The present invention is to solve the above problems, and to provide a non-aqueous paste composition using a polyvinyl alcohol as a main binder, as well as a non-aqueous paste composition using a polymer resin as a binder and an alcohol as a solvent, Porous calcium phosphate scaffold with open pore structure with pores connected to each other by using a device that can produce uniform paste of soluble calcium phosphate powder, realize uniform sponge coating property, and perform compression / expansion process and rolling process together. The purpose is to provide.

Features of the present invention for achieving the above object is 20 to 60% by weight calcium phosphate powder based on the total weight of the paste, 30 to 70% by weight of distilled water as a solvent, polyvinyl alcohol (hereinafter referred to as 'PVA') 1-10% by weight, 0.1-2% by weight of dispersant, 0.5-10% by weight of one or more cracking inhibitors selected from ethylene glycol, glycerin, formamide, dimethylformamide, and cellulose derivatives as co-binding agents. It is in an aqueous calcium phosphate paste composition comprising 0.2 to 5% by weight.

And at least one solvent selected from 20 to 60% by weight of calcium phosphate powder, methanol, ethanol, isopropanol, isobutanol, n-propanol, n-butanol, methyl acetate, ethyl acetate, butyl acetate based on the total weight of the paste. ~ 70% by weight, 1 to 10% by weight of at least one polymer resin selected from epoxy, urethane, silicone, polyester, polyether, polyethylene, melamine, and acrylic as binders, 0.1 to 2% by weight of dispersant, 0.5 to 10% by weight of a flow additive, which is a polysiloxane derivative, 0.2 to 1 or more polymerization initiators selected from azo, peroxide, sulfite, and amine systems It is characterized by a non-aqueous calcium phosphate paste comprising 5% by weight.

In addition, another feature of the present invention is the step of heat dissolving in 30 to 70% by weight of distilled water using 1 to 10% by weight of polyvinyl alcohol as a binder based on the total weight; Adding 0.2-5% by weight of cellulose derivatives as a co-binder to stir and dissolve; Adding and stirring 0.1 to 3 wt% dispersant; Adding 1 to 10% by weight of the crack inhibitor; 20 to 60% by weight of the calcium phosphate powder is added, and the method for producing an aqueous calcium phosphate paste comprising the step of uniformly mixing by stirring or kneading.

And, using 1 to 10% by weight of the polymer resin as a binder, adding to 30 to 70% by weight of the solvent used in the non-aqueous paste, stirring and dissolving; Adding 0.1 to 3% by weight of the dispersant and stirring; Adding 0.1 to 7% by weight of a polysiloxane compound (polysiloxane derivatives) as a flow additive and stirring; 20 to 60% by weight of calcium phosphate powder is added, and the method for producing a non-aqueous calcium phosphate paste comprising the step of mixing uniformly by stirring or kneading.

The calcium phosphate is a biphasic calcium phosphate, a mixture of hydroxyapatite, alpha tricalcium phosphate, beta tricalcium phosphate, beta tricalcium phosphate, apatite hydroxide and beta tricalcium phosphate. calcium phosphate, tetracalcium phosphate, calcium pyrophosphate, calcium polyphosphate, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous Monocalcium phosphate monohydrate, SiO ₂ -CaO-P ₂ O ₅ based bioglass, SiO ₂ -CaO-P ₂ O ₅ -B ₂ O ₃ based bioglass, SiO ₂ -CaO-P ₂ O ₅ -Na ₂ O-based bioglass, SiO ₂ -CaO-P ₂ O ₅ -K ₂ O-based bioglass, SiO ₂ -CaO-P ₂ O ₅ -Li ₂ O-based bioglass, SiO ₂ -CaO-P ₂ O ₅ -MgO-based bioglass or other SiO ₂ -CaO-P ₂ O ₅ based on the basic composition _{B 2 O 3, Na 2 O} , K 2 O, Li 2 O, MgO is selected from 1, At least 1 type is selected and used from the bioglass which mixed more than 1 type.

And a dispersing agent selects 1 or more types from a polyacrylic ammonium salt, a polycarboxylic acid ammonium salt, a trimethoxy phosphate, a trimethoxy phosphite, a triethoxy phosphate, and a triethoxy phosphite.

The molecular weight of PVA used in the aqueous calcium phosphate paste is selected in the range of 1,500 to 25,000, and after being added to distilled water, it is dissolved transparently while stirring at 30 to 80 ° C.

In addition, the cellulose compound is methyl cellulose, methyl ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxy cellulose, carboxymethyl cellulose, carboxyethyl One or more types are selected and used out of cellulose.

Polymer resins used as binders for non-aqueous calcium phosphate pastes include epoxy resins, epoxy methadiacrylates, poly (bisphenol A-co-epichlorohydrin) based on epoxy resins, diglycidyl ether of bisphenol A-based epoxy resins, epoxyacrylate oligomer, phenol-urethane resin, urethane resin, polyurethane resin, diurethane dimethacrylate, allyl aliphatic urethane diacrylate, urethane acrylate, aliphatic urethane methacrylate, aliphatic urethane diacrylate, polyurethane diol, polydimethyl siloxane as silicone resin, silicone acrylate, silocone diacrylate , Silocone hexaacrylate, polyester styrene resin, polyester acrylate, polyester triacrylate, polyester tetraacrylate, polyester hexaacrylate, polyester urethane acrylate, polyether acrylate as polyether resin, polyether tetraacrylate, polyether urethane acrylate, polyethylene resin as polyethylene resin , poly ethylene glycol acrylate, polyethylene glycol diacrylate, polyethylene glycol methyl ether acrylate, polyethylene-co-methacrylate, polyethylene-co-ethyl acrylate, polyethylene-co-methyl acrylate, melamine resin, trichloromelamine, polymelamine-co-formaldehyde, hexakismethoxymethyl Use at least one selected from melamine, butylated melamine, isobutylated melamine, isobutylated urea melamine, and trinaphthylmethyl melamine.

In addition, the acrylic monomer which is a binder of the non-aqueous calcium phosphate paste is methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hydroxyehtyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, allyl methacrylate, ethylene glycol dimethacrylate and hydroxyethyl methacrylate. , glycidyl methacrylate, hexandiol diacrylate, hexandiol dimethacrylate, trimethylopropane trimethacrylate, ethyl-3-ethoxy acrylate, triethylene glycol dimethacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, ethoxyethyl acrylate, ethoxyethyl methacrylate, ethylhexyl acrylate, ethylhexyl methacrylate, lauacrylate , ethylene diacrylate, ethyl-3-amino-3-ethoxy acrylate, tert-butyl acrylate, trimethylsilyl methacrylate, tripropylene glycol diacrylate, hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, phenyl methacrylate, tetraethylene glycol diacrylate, polyehtylene glycol phenyl et her acrylate, 2-hydroxy-3-phenoxypropyl acrylate, ethylene glycol dicyclopentenyl ether acrylate, ethylene glycol dicyclopentenyl ether methacrylate, sodium acrylate, sodium methacrylate, tridecyl methacrylate, hexyl acrylate, hexyl methacrylate, isodecyl acrylate, isodecyl methacrylate, cyclohexyl methacrylate, benzyl methacrylate Select one or more of benzyl 2-ethyl acrylate, ethyl 2-N-propyl acrylate, benzyl 2-N-propyl acrylate, zinc acrylate, butanediol diacrylate, butanediol dimethacrylate, vinyl acrylate and vinyl methacrylate.

In addition, another feature of the present invention is a scaffold manufacturing apparatus, the paste tank on which the calcium phosphate paste is loaded, the metal mesh plate installed to be spaced apart from the bottom of the paste tank by a predetermined distance, and the metal mesh plate up and down Vertical vertical moving means, the roller is installed on one side of the upper fixed position of the metal mesh plate spaced apart from the upper metal mesh plate by reciprocating the roller and the roller driving means for pressing the sponge on the upper metal mesh plate, the upper metal mesh plate And a punch and a punch driving means positioned at and positioned so that the sponge on the top of the metal mesh plate repeats pressing and restoring a plurality of times.

In addition, a method of manufacturing an aqueous calcium phosphate scaffold by coating a calcium phosphate paste prepared by the composition and manufacturing method as described above to a polyurethane sponge, vertical transfer of the porous metal mesh plate constituting the scaffold manufacturing apparatus Moving the device up and down over the paste tank by means to adjust the position of the metal mesh plate to be 10-50% of the sponge thickness to be used from the top of the metal mesh plate to the surface of the calcium phosphate paste; Placing a polyurethane sponge on the metal mesh plate above and repeatedly compressing / expanding the sponge by vertical movement of the plate-shaped punch to infiltrate the paste into the sponge and uniformly coat the sponge; Rolling the sponge with a roller to remove the excess paste infiltrated into the sponge after the metal mesh plate is moved to the upper position so as to be spaced apart from the paste; Repeatedly rolling up and down with the punch to remove the window film formed in the sponge pores after rolling; Drying the sponge coated with calcium phosphate paste at 5 to 60 ° C. for 30 minutes to 5 hours; Including the sponge is heated in a firing furnace to heat up at a high temperature of 1000 ~ 1350 ℃.

The non-aqueous calcium phosphate scaffold manufacturing method is the same as the above-described method for producing the aqueous calcium phosphate scaffold, and the polymerization is initiated at least one selected from azo and peroxide-based pastes as described above. There is only a difference between adding 0.5 to 5% by weight of zero, and thermally polymerizing in a drying step for 30 minutes to 4 hours at 60 to 100 ° C. in an inert gas atmosphere such as air to nitrogen and argon.

In the heat treatment step, the polyurethane sponge coated with calcium phosphate paste is preferably heated at a relatively slow speed of 1 to 5 ° C./min in the 250 to 400 ° C. section, and 5 to 10 ° C./min in the 400 to 600 ° C. section. It is preferable to increase the temperature at a rate of, and the temperature is raised at a rate of 10 ~ 15 ℃ / min in the section of 600 ~ 1350 ℃, and maintained for 30 minutes to 4 hours at a temperature of 1000 ~ 1350 ℃, the final target temperature.

According to the present invention having the configuration as described above can be obtained a porous calcium phosphate scaffold having a pore structure connected to the pores, the scaffold is attached to the growth of the blood vessels and macroscopic pores in the pores when placed in the human body, It is a very useful manufacturing method in the field of dentistry and orthopedics because it provides a very easy structure for the growth of autologous bone tissue to secure very high bone regeneration and autogenous bone occupancy after a certain period of time. In addition, the micro-pores of the scaffold surface prepared as described above provides a surface roughness very useful for the attachment of osteoblasts, providing fast and excellent osteoblast adhesion, as well as smooth the circulation of blood and body fluids inside the scaffold It can induce uniform bone regeneration at the same time outside and outside. In addition, since it provides a very advantageous structure for coating a bone growth factor on the scaffold surface, it can be said to be a very promising manufacturing method as a tissue engineering bone marrow restoration in the future.

Furthermore, according to the above scaffold manufacturing apparatus, since the paste is coated on the sponge appropriately and uniformly, the pore characteristics of the manufactured scaffold are excellent, and a series of coating processes for manufacturing the scaffold are collectively performed in one machine. Therefore, there is an effect that the productivity is increased.

1a to 1c is a schematic view of the apparatus for manufacturing a scaffold according to the present invention.
Figure 2 is an enlarged photograph 200 times of a polyurethane sponge coated with an aqueous calcium phosphate paste according to the present invention.
Figure 3 is an enlarged photograph 200 times the polyurethane sponge coated with a non-aqueous calcium phosphate paste according to the present invention.
4 is a thermal analysis graph of the polyurethane sponge used in the present invention.
FIG. 5 is an electron micrograph of a polyurethane sponge coated with an aqueous or non-aqueous calcium phosphate paste in accordance with the present invention after being heat-treated at 1250 ° C. and then expanded to 30 times (a) and 2,000 times (b), respectively. FIG.
Figure 6 is a picture of 1 after transplanting osteoblasts and cultured scaffold prepared according to the present invention.

An embodiment of the present invention will be described in more detail with reference to the accompanying drawings. However, the following examples are merely to illustrate the invention, not limited to the examples specified in the present invention.

Figure 1a is a partial cross-sectional view showing a scaffold manufacturing apparatus of the present invention, Figure 1b is a side cross-sectional view showing the roller drive means of Figure 1a and Figure 1c is an enlarged perspective view of the main portion showing the internal structure of the paste tank.

The scaffold manufacturing apparatus according to the present invention, wherein the scaffold manufacturing apparatus is a paste tank 10, the calcium phosphate paste (P) is supported, the bottom surface of the paste tank 10 and a predetermined distance apart The metal mesh plate 20, the vertical conveying means 30 for moving the metal mesh plate 20 up and down, and the metal mesh plate 20 are installed on one side of the metal mesh plate 20 so as to reciprocate the upper portion of the metal mesh plate 20. The roller 40 and the roller driving means 50 to move, and the punch 60 and the punch driving means 70 is located on the metal mesh plate 20 above the vertical movement.

In the vertical conveying means 30 is a connecting portion 31 vertically connected to the metal mesh plate 20, the guide 32 is installed vertically inside or outside the paste tank 10, the guide ( A slider 33 which is reciprocated along the 32 and connected to the connecting portion 31, and a driving means 34 which allows the slider 33 to reciprocate along the guide 32. The vertical conveying means uses a screw shaft as a guide 32 and the slider 33 uses a screw groove formed at its inner circumference to engage the screw shaft described above, and the motor 34 rotates the screw shaft with the driving means 34. It may be used, as a guide 32 using a guide rail installed vertically, the slider 33 is connected to the connecting portion 31 to move up and down along the guide rail as described above and the drive means 34 of the cylinder Using piston rod The slider may be integrally fastened to the piston rod, the motor may be used as the driving means, and the LM guide may be used as the guide and the slider. In addition, those skilled in the art may use various devices that can vertically reciprocate. Omit.

On the other hand, the connecting portion 31 connected to one side of the metal mesh plate 20 in the vertical conveying means is connected to the driving means 34, but the other side may be connected only to the guide and the slider, not connected to the driving means 34. have.

The roller driving means 50 is positioned on the rack 51 in connection with the rack 51 installed horizontally on the upper inner circumference or the outer circumference of the paste tank 10 and the driving shaft of the roller 40. It comprises a pinion 52, a motor 53 installed in the pinion 52 to rotate the pinion 52, in addition to the roller drive means for rotating the roller by a motor, the motor is installed The block may be left / right reciprocated using a cylinder, and this structure may be implemented by those skilled in the art in various ways, and thus, the above description is omitted.

In addition, the punch 60 is for pressing the sponge 80 on the metal mesh plate 20, the lower surface of the punch 60 is formed flat and the punch 60 is the upper portion of the paste tank 10 It is formed integrally coupled to the rod 63 of the cylinder 62 fixed to the bracket 61 or the like, or integrally coupled to the press cam device fixed to the upper portion of the paste tank 10 by the bracket 61 or the like. The structure may also be implemented by those skilled in the art in various ways, and thus other examples are omitted.

In the drawing, reference numeral 12 is a guide groove through which the roller is guided.

Hereinafter, a method for manufacturing a scaffold using the above apparatus will be described.

Preparation of Aqueous Calcium Phosphate Paste

According to the composition shown in Table 1, after adding 1-7 weight% of PVA binders to distilled water, respectively, it stirred, heating at 50 degreeC with a heat stirrer, dissolving transparently, and cooling, and manufacturing a PVA solution.

Then, 0.1 to 3% by weight of methylcellulose, more preferably 0.2 to 0.5% by weight, is added to the PVA solution as a cellulose cobinder and stirred until completely dissolved.

0.1 to 3% by weight of polycarboxylic acid ammonium salt, more preferably 0.5 to 0.8% by weight, is added as a dispersing agent, and 2 to 5% by weight of ethylene glycol is added and stirred as a crack inhibitor. Was prepared.

BCP powder in the calcium phosphate-based powder is added to 20 to 70% by weight, more preferably 40 to 60% by weight based on the total content, and slowly and uniformly mixed with a double screw blade to prepare a final aqueous calcium phosphate paste. .

Non-aqueous  Preparation of Calcium Phosphate Paste

According to the composition of Table 2, 1 to 7% by weight of the urethane acrylate resin is dissolved in 30 to 70% by weight of isobutanol based on the total weight, and then 0.5 to 2% by weight of triethoxy phosphate is added as a dispersant and further stirred. . Add 0.5 to 5% by weight, more preferably 1 to 3% by weight of polydimethylsiloxane as a flow additive, and add 0.3 to 0.8% by weight of benzoylperoxide as a polymerization initiator and dissolve completely with stirring. . BCP powder in the calcium phosphate-based powder is added in an amount of 20 to 70% by weight, more preferably 40 to 60% by weight based on the total content, and slowly and uniformly mixed with a double screwed blade to prepare a final aqueous calcium phosphate paste.

Calcium phosphate paste coated on sponge

First, a 60 ppi polyurethane sponge was immersed in 10% sodium hydroxide solution, surface treated in an ultrasonic bath for 10 minutes, taken out, firstly washed in running water, then immersed in distilled water for 10 minutes in an ultrasonic bath, and dried. Sponge was prepared.

In order to uniformly infiltrate the aqueous or non-aqueous calcium phosphate paste into the sponge as described above, the sponge is impregnated into the paste using the apparatus of FIG. 1 and then repeatedly compressed and expanded the sponge. To perform.

At this time, in order to impregnate the sponge 80 with an appropriate amount, the height of the metal mesh plate 20 is moved toward the paste tank 10 so that the metal mesh plate 20 presses the paste P so that the metal mesh plate ( The paste is allowed to soak up between the mesh pores of the 20), the gap between the paste spread surface and the metal mesh plate 20 is 10 to 50% of the thickness of the sponge 80 to be coated, preferably 20% of the sponge thickness The position of the metal mesh plate 20 is adjusted so that it may be.

Thereafter, the sponge 80 is placed on the metal mesh plate 20 and the punch 60 is repeatedly beated up and down 10 to 20 times so that the lower paste is uniformly coated on the entire sponge 80. The lowering position of the punch 60 is lowered to a position where the sponge 80 is compressed to a thickness of 10 to 50% of the original thickness so that the paste applied to the bottom surface of the sponge 80 is in contact or capillary phenomenon with the upper surface of the sponge. To be slowly coated.

When the paste is uniformly coated on the sponge 80 through this process, the metal mesh plate 20 is elevated after being elevated to a position spaced apart from the paste P, and then fixed, and then the roller 40 is fixed. The sponge 80 is pressed and rolled to remove excess paste in the sponge 80 so that the paste is coated along the sponge 80 skeleton.

Then, the paste-coated sponge 80 is dried at 5 to 60 ° C. when using an aqueous calcium phosphate paste, and at 60 to 100 ° C. under an inert gas atmosphere such as air to nitrogen and argon when using a non-aqueous calcium phosphate paste. Dry by thermal polymerization for 30 minutes to 4 hours.

FIG. 2 is a scanning electron microscope photograph of a paste according to the composition of Table 1 coated on a polyurethane sponge using the scaffold manufacturing apparatus of FIG. 1, and then dried 200 times.

Overall, as the content of PVA increases from 1% by weight to 7% by weight, the BCP particles are effectively trapped to show uniform and smooth coating properties.

When the BCP powder content was 40% by weight, the PVA content of 3% by weight or less showed uneven coating properties with many surface defects, while the PVA content of 5% by weight or more was relatively good but still exhibited pores and cracks.

When 50% by weight of BCP powder was included, pores and cracks appeared at 3 wt% or less, but at 5 wt% or more, very good BCP paste coating properties were shown.

In the paste containing 60% by weight of BCP powder, the powder content was too high to uniformly disperse the particles in the paste, which caused the spreading of the paste to deteriorate, resulting in agglomeration of particles even after coating on the sponge. The content was so high that as a result large cracks occurred due to large shrinkage during the drying process.

In this example, the best paste coating properties without cracks and pores were exhibited under the condition that the PVA content was 5% by weight and the BCP powder content was 50% by weight (Example 3).

FIG. 3 is a scanning electron micrograph of the paste prepared according to the composition of Table 2 by the scaffold manufacturing apparatus of FIG. 1 coated on a polyurethane sponge and dried 200 times.

In general, as the content of urethane acrylate increases from 1% by weight to 7% by weight, uniform and smooth coating properties are exhibited.

When the BCP powder content was 40% by weight, the coating property of the urethane acrylate content was less than 3% by weight, and the coating of the edges of the sponge was uneven while the content of the urethane acrylate resin was more than 5% by weight. .

When 50% by weight of BCP powder was included, the porosity and cracks were very high at 3% by weight or less, some pores were found at 5% by weight or more, and very good BCP paste coating properties were obtained at 7% by weight or more. .

Paste containing 60% by weight of BCP powder showed better coating properties at 3% by weight of resin, but resulted in agglomeration of particles due to a drop in fluidity due to too high powder content as a whole.

In this example, the best paste coating properties without cracks and pores were obtained under the condition that the urethane acrylate resin content was 7% by weight and the BCP powder content was 50% by weight.

Heat Treatment of Polyurethane Sponge Coated with Calcium Phosphate Paste

Figure 4 is a graph showing the results of differential thermal analysis, thermogravimetric analysis of polyurethane sponges coated with aqueous to non-aqueous calcium phosphate paste according to the present invention.

When the polyurethane sponge is heat treated at a temperature increase rate of 5 ° C./min, it shows a rapid weight loss of about 80% in the range of 280 to 400 ° C. due to volatilization of the polyurethane sponge, and then to about 20% at 400 to 550 ° C. Close weight loss occurs due to volatilization of the binder.

Therefore, when heat-treating the polyurethane sponge coated with calcium phosphate paste, it is preferable to increase the temperature at a relatively slow speed of 1 to 5 ℃ / min in the 250 ~ 400 ℃ section, 5 ~ 10 ℃ / min in the 400 ~ 600 ℃ section It is preferable to increase the temperature at a rate of, and the temperature is raised at a rate of 10 ~ 15 ℃ / min in the section of 600 ~ 1350 ℃, and maintained for 30 minutes to 4 hours at a temperature of the final target temperature of 1000 ~ 1350 ℃.

5 is an electron microscope photograph of a scaffold prepared by coating a water-based or non-aqueous calcium phosphate paste and gradually raising the dried polyurethane sponge to a final target temperature of 1250 ° C. and then heat-treating at 1250 ° C. for 30 hours, respectively. It is enlarged 2,000 times.

The better the coating property of the aqueous to non-aqueous paste before the heat treatment, the more uniform the skeleton structure was without any crack after the heat treatment. In the case of using a 60 ppi sponge, a scaffold having a macro pore size of 350 to 600 μm after heat treatment could be prepared, and the structure having micro pores was confirmed by looking at the enlarged photograph of the skeleton portion. The macropores of the open pore structure connected to each other provide a space for blood vessels, osteoblasts, and autologous bone tissue to grow into the pores when placed in the human body, and micropores help circulation of blood, body fluids, and osteoblasts to the skeleton Provides surface roughness that can adhere well to surfaces.

Figure 6 is an enlarged photo of the scaffold after a week after transplanting osteoblasts to the scaffold prepared according to the present invention and cultured in the culture solution, osteoblasts attached to the scaffold surface and then along the surface It proliferates and covers the entire scaffold skeleton.

In addition, it can be seen that the tissue form between the cells showing typical excellent cell adhesion and proliferation, the macro dog by the method of manufacturing the scaffold using the polyurethane sponge as judged that the osteoblasts adhered well to the deep inside the pores It can be seen that the pore structure provides a very useful structure for bone regeneration.

At the same time, it was confirmed that the micropore structure of the scaffold surface provides very effective surface roughness for osteoblast adhesion, and thus the osteoblast adhesion is very excellent.

10: paste tank P: paste
20: metal mesh plate 30: vertical conveying means
40: roller 60: punch

Claims (10)

A paste tank 10 on which calcium phosphate paste is supported,
A metal mesh plate 20 installed to be spaced apart from the bottom surface of the paste tank 10 by a predetermined interval,
Vertical transfer means 30 to move the metal mesh plate 20 up and down,
The roller 40 and the roller driving means 50 installed on one side of the metal mesh plate 20 to reciprocate while rotating the upper portion of the metal mesh plate 20,
Scaffold manufacturing apparatus characterized in that it comprises a punch and punch driving means (70) located on the upper side of the metal mesh plate (20). Using the scaffold manufacturing apparatus of claim 1,
Moving the porous metal mesh plate up and down on the paste tank to adjust the position such that it is 10-50% of the sponge thickness to be used from the top of the metal mesh plate to the surface of the aqueous calcium phosphate paste;
Placing a polyurethane sponge on the metal mesh plate above and repeatedly compressing / expanding the sponge by vertical movement of the plate-shaped punch to infiltrate the paste into the sponge and uniformly coat the sponge;
Rolling the sponge with a roller to remove the excess paste infiltrated into the sponge after the metal mesh plate is moved to the upper position so as to be spaced apart from the paste;
Repeatedly rolling up and down with the punch to remove the window film formed in the sponge pores after rolling;
Drying the sponge coated with calcium phosphate paste at 5 to 60 ° C;
The method of manufacturing a scaffold comprising the step of heating the above-mentioned sponge to a firing furnace to heat up at a high temperature of 1000 ~ 1350 ℃. The method according to claim 2, wherein the aqueous calcium phosphate paste,
20 to 60% by weight calcium phosphate powder, based on the total weight of the paste composition
30 to 70% by weight of distilled water as a solvent,
1 to 10% by weight of polyvinyl alcohol (hereinafter referred to as 'PVA') as a binder,
0.1 to 2% by weight of a dispersing agent selected from one or more of polyacrylic ammonium salts, ammonium polycarboxylic acid salts, trimethoxy phosphate, trimethoxy phosphite, triethoxy phosphate and triethoxy phosphate,
0.5 to 10% by weight of at least one crack inhibitor selected from ethylene glycol, glycerin, formamide, and dimethylformamide,
Copolymer is methyl cellulose, methyl ethyl cellulose, hydroxy methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxy cellulose, carboxymethyl cellulose, carboxyethyl cellulose A method for producing a scaffold comprising 0.2 to 5% by weight of cellulose derivatives used by selecting the above. The method according to claim 2, wherein the aqueous calcium phosphate paste,
Heat dissolving in 30 to 70% by weight of distilled water using 1 to 10% by weight of polyvinyl alcohol as a binder based on the total weight;
Adding 0.2-5% by weight of cellulose derivatives as a co-binder to stir and dissolve;
Adding and stirring 0.1 to 3% by weight of a dispersing agent selected from one or more selected from polyacrylic ammonium salt, polyammonium carbonate salt, trimethoxy phosphate, trimethoxy phosphite, triethoxy phosphate and triethoxy phosphite ;
Adding 1 to 10% by weight of at least one crack inhibitor selected from ethylene glycol, glycerin, formamide, and dimethylformamide;
20 to 60% by weight of a calcium phosphate powder and a method for producing a scaffold comprising the step of uniformly mixing by stirring or kneading. Using the scaffold manufacturing apparatus of claim 1,
Moving the porous metal mesh plate up and down on the paste tank to adjust the position such that it is 10-50% of the sponge thickness to be used from the top of the metal mesh plate to the surface of the non-aqueous calcium phosphate paste;
Placing a polyurethane sponge on the metal mesh plate above and repeatedly compressing / expanding the sponge by vertical movement of the plate-shaped punch to infiltrate the paste into the sponge and uniformly coat the sponge;
Rolling the sponge with a roller to remove the excess paste infiltrated into the sponge after the metal mesh plate is moved to the upper position so as to be spaced apart from the paste;
Repeatedly rolling up and down with the punch to remove the window film formed in the sponge pores after rolling;
A drying step of thermally polymerizing the sponge coated with calcium phosphate paste for 30 minutes to 4 hours at 60 to 100 ° C. in an inert gas atmosphere such as air to nitrogen and argon;
The method of manufacturing a scaffold comprising the step of heating the above-mentioned sponge to a firing furnace to heat up at a high temperature of 1000 ~ 1350 ℃. 6. The non-aqueous calcium phosphate paste of claim 5, wherein
20 to 60% by weight calcium phosphate powder, based on the total weight of the paste composition
30 to 70% by weight of one or more solvents selected from methanol, ethanol, isopropanol, isobutanol, n-propanol, n-butanol, methyl acetate, ethyl acetate, butyl acetate,
1 to 10% by weight of one or more polymer resins selected from epoxy, urethane, silicone, polyester, polyether, polyethylene, melamine, and acrylic as binders,
0.1 to 2% by weight of a dispersing agent selected from one or more of polyacrylic ammonium salts, ammonium polycarboxylic acid salts, trimethoxy phosphate, trimethoxy phosphite, triethoxy phosphate and triethoxy phosphate,
0.5 to 10% by weight of a flow additive which is a polysiloxane derivatives,
A method for producing a scaffold comprising 0.2 to 5% by weight of at least one polymerization initiator selected from azo, peroxide, sulfite and amine systems. The method of claim 5, wherein the non-aqueous calcium phosphate paste,
Methanol, ethanol, isopropanol, isobutanol, adding to 30-70% by weight of at least one solvent selected from n-propanol, n-butanol, methyl acetate, ethyl acetate, butyl acetate, stirring and dissolving;
0.1-3% by weight of a dispersing agent selected from polyacrylic ammonium salt, ammonium polycarboxylic acid salt, trimethoxy phosphate, trimethoxy phosphite, triethoxy phosphate, triethoxy phosphate and used and added ;
Adding 0.1 to 7% by weight of a polysiloxane compound (polysiloxane derivatives) as a flow additive and stirring;
20 to 60% by weight of calcium phosphate powder, and a method for producing a scaffold comprising the step of uniformly mixing by stirring or kneading. The calcium phosphate according to claim 3 or 6,
Hydroxyapatite, alpha-tricalcium phosphate, beta-tricalcium phosphate, biphasic calcium phosphate, tetracalcium phosphate mixed with apatite hydroxide and beta tricalcium phosphate Phosphate (tetracalcium phosphate), calcium pyrophosphate, calcium polyphosphate, dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, monocalcium phosphate monohydrate monocalcium phosphate monohydrate), SiO ₂ -CaO-P ₂ O _{5 type} bioglass, SiO ₂ -CaO-P ₂ O ₅ -B ₂ O _{3 type} bioglass, SiO ₂ -CaO-P ₂ O ₅ -Na ₂ O type _{bio-glass, SiO 2 -CaO-P 2 O} 5 -K 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -Li 2 O -based _{bioglass, SiO 2 -CaO-P 2 O} 5 -MgO -based by- Glass, and other SiO ₂ -CaO-P ₂ O ₅ based on the basic composition _{B 2 O 3, Na 2 O} , K 2 O, Li 2 O, MgO at least one selected from a bioglass mixture of at least one member selected from Calcium phosphate paste composition, characterized in that the use. The method of claim 6, wherein the polymer resin is epoxy resin, epoxy methadiacrylate, poly (bisphenol A-co-epichlorohydrin) based on epoxy resin, diglycidyl ether of bisphenol A-based epoxy resins, epoxyacrylate oligomer, urethane resin phenol-urethane resin, urethane resin, polyurethane resin, diurethane dimethacrylate, allyl aliphatic urethane diacrylate, urethane acrylate, aliphatic urethane methacrylate, aliphatic urethane diacrylate, polyurethane diol, polydimethyl siloxane, silicone acrylate, silocone diacrylate, silocone hexaacrylate, polyester As polyester resin, polyester styrene resin, polyester acrylate, polyester triacrylate, polyester tetraacrylate, polyester hexaacrylate, polyester urethane acrylate, polyether resin as polyether acrylate, polyether tetraacrylate, polyether urethane acrylate, polyethylene resin as polyethylene resin, polyethylene glycol acrylate, polyethylene glycol diacryl ate, polyethylene glycol methyl ether acrylate, polyethylene-co-methacrylate, polyethylene-co-ethyl acrylate, polyethylene-co-methyl acrylate, melamine resin, melamine resin, trichloromelamine, polymelamine-co-formaldehyde, hexakismethoxymethyl melamine, butylated melamine, isobutylated One or more selected from melamine, isobutylated urea melamine, trinaphthylmethyl melamine, and acrylic monomers are methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hydroxyehtyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, allyl methacrylate , ethylene glycol dimethacrylate, hydroxyethyl methacrylate, glycidyl methacrylate, hexandiol diacrylate, hexandiol dimethacrylate, trimethylopropane trimethacrylate, ethyl-3-ethoxy acrylate, triethylene glycol dimethacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, ethoxyethyl acrylate, ethoxyethyl methacrylate, ethylhex ethylhexyl methacrylate, lauryl acrylate, lauryl methacrylate, ethylene diacrylate, ethyl-3-amino-3-ethoxy acrylate, tert-butyl acrylate, trimethylsilyl methacrylate, tripropylene glycol diacrylate, hexafluoroisopropyl acrylate, hexafluoroisopropyl methacrylate, phenyl methacrylate, tetraethylene glycol diacrylate, polyehtylene glycol phenyl ether acrylate, 2-hydroxy-3-phenoxypropyl acrylate, ethylene glycol dicyclopentenyl ether acrylate, ethylene glycol dicyclopentenyl ether methacrylate, sodium acrylate, sodium methacrylate, tridecyl methacrylate, hexyl acrylate, hexyl methacrylate, isodecyl acrylate, isodecyl methacrylate, cyclohexyl methacrylate, benzyl at least one selected from methacrylate, benzyl 2-ethyl acrylate, ethyl 2-N-propyl acrylate, benzyl 2-N-propyl acrylate, zinc acrylate, butanediol diacrylate, butanediol dimethacrylate, vinyl acrylate and vinyl methacrylate. Calcium Phosphate Paste Composition. The method of claim 2 or 5, wherein the heat treatment step
The polyurethane sponge coated with calcium phosphate paste is preferably heated at a relatively slow rate of 1 to 5 ° C./min in the 250 to 400 ° C. section, and is heated at a rate of 5 to 10 ° C./min in the 400 to 600 ° C. section. Preferably, the temperature is raised at a rate of 10 ~ 15 ℃ / min in the interval of 600 ~ 1350 ℃, and the scaffold manufacturing method characterized in that to maintain for 30 minutes to 4 hours at a temperature of 1000 ~ 1350 ℃ the final target temperature .

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