WO2018093159A1 - Biologically active glass powder, amorphous medical material for substituting biological hard tissue defect using same, artificial bone tissue using same, and method for manufacturing same - Google Patents

Abstract

The present invention relates to a biologically active glass powder, an amorphous medical material for substituting a biological hard tissue defect using the same, an artificial bone tissue, and a method for manufacturing the same and, more specifically, to a biologically active glass powder, which is used in a medical material for substituting a biological hard tissue defect, the medical material being capable of manufacturing an artificial bone tissue for bio-transplantation having excellent adhesion to an in-vivo bone tissue, biocompatibility, and mechanical strength, to an amorphous medical material for substituting a biological hard tissue defect, the amorphous medicalmaterial being prepared by using the biologically active glass powder, to a crystalline type artificial bone tissue manufactured using the amorphous medical material for substituting a biological hard tissue defect, and to a method for manufacturing the crystalline type artificial bone tissue.

Description

Bioactive glass powder, medicinal material for replacing amorphous biotissue defect using same, artificial bone tissue using same and manufacturing method thereof

The present invention provides a bioactive glass powder for use in a substitute for living hard tissue defects, which can produce artificial bone tissue for biograft having excellent adhesion, biocompatibility, and mechanical strength with bone tissue in vivo, and using the same. The present invention relates to a medicinal material for replacing a non-crystalline biohard tissue defect, a crystalline artificial bone tissue prepared using the crystalline material for replacing a non-crystalline biohard tissue defect, and a method of manufacturing the same.

The hard tissues that make up the human body are composed of 67% of inorganic and 33% of organic matter, and the inorganic material is composed of apatite mainly composed of Ca / P. Due to the high composition ratio of minerals, it is possible to substitute synthetic hydroxyapatite when hard tissue defects occur. However, synthetic hydroxyapatite has a disadvantage in that it is difficult to apply to various sites requiring mechanical stability due to low compressive strength.

Hydroxyapatite is a representative bone conducting substance that bonds directly to bones when they engage with peripheral defects in the implanted site. These materials cause bone fusion when they are in direct contact with the defect, or they can damage the surrounding bone by micro-motion of the implant. Therefore, it is possible to enhance the effectiveness of the treatment by customizing the design exactly fit the implantation site.

Typical ceramic materials are characterized by excellent compressive strength, hardness, and wear resistance. In addition, since it exists in the form of an oxide, it is excellent in corrosion resistance by chemical substances. The excellent physical and chemical stability of ceramic materials has the advantage of greatly extending their life when used in various components. However, due to the rigidity of the material is difficult to process, it is impossible to manufacture a complex molded body.

Since the stiffness of the ceramic material is indicated by heat treatment, it is common to complete molding before heat treatment, and some processing may be performed by using a polishing method after heat treatment. The ceramic molded body may be prepared by simply pressing the powder before heat treatment, or by preparing a slurry to cast, injection molding or extrusion molding. The molded article produced in the above manner is heat treated according to the sintering temperature of the raw material to complete the manufacture. When molding the entire heat treatment design, a mold capable of realizing this is essential, and only a corresponding design can be manufactured.

If various designs of the product are to be implemented, processing after heat treatment should be applied. Due to the ceramic characteristics, this method has a disadvantage in that it takes time and cost. In addition, the high hardness of the surface may cause a defective rate due to processing because the possibility of defects occurring during excessive processing is high. If a defect occurs after a human transplant due to processing defects, the transplantation site is not only severely damaged but also needs to be reoperated.

In particular, when manufacturing a hard tissue replacement material can be said to be tailored to exactly match the defects.

The present invention has been made to solve the above-described problems, it is optimal to produce an artificial bone tissue having excellent physical properties, as well as processability, moldability, but excellent adhesion to the bone tissue (bio) tissue in vivo An object of the present invention is to provide a bioactive glass powder having a composition and a composition ratio thereof, and a biomaterial for replacing the amorphous biohard tissue defects prepared using the same. Another object of the present invention is to provide a biograft artificial bone tissue having crystallinity and a method of manufacturing the same by using the biomaterial for replacing a hard tissue defect.

The bioactive glass powder of the present invention for solving the above problems includes a pulverized product of a melt obtained by melting a mixture containing MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ .

In one preferred embodiment of the invention, the mixture is MgO 4.5 ~ 6.5 wt%, CaO 41 ~ 43 wt%, SiO ₂ 34 to 36.2 wt%, P ₂ O ₅ 13.5-17 wt%, CaF ₂ 0.9-2.5 wt% and B ₂ O ₃ 0.2-1.5 wt%.

In one preferred embodiment of the invention, the mixture is MgO 4.5 ~ 6.5 wt%, CaO 41 ~ 43 wt%, SiO ₂ 30.5 to 32.5 wt%, P ₂ O ₅ 18.5 to 19.8 wt%, CaF ₂ 0.5 to 1.5 wt% and B ₂ O ₃ It may also comprise 0.2 to 1.5% by weight.

In one preferred embodiment of the invention, the mixture may further comprise Na ₂ O.

In one preferred embodiment of the present invention, the bioactive glass powder may have an average particle diameter of 0.5 ㎛ ~ 10 ㎛.

Another object of the present invention, a biomaterial for replacing a hard tissue defect includes a bioactive glass powder of the above various forms.

As a preferred embodiment of the present invention, the biomaterial for replacing the hard tissue defects of the present invention includes an amorphous molded body obtained by heat-treating the compressed molding of the bioactive glass powder to a temperature below the glass transition temperature of the bioactive glass powder in the molding. can do.

In one preferred embodiment of the present invention, the amorphous molded product is a molded product obtained by heat-treating the compression molded product at 680 ° C to 720 ° C. When the molded product is a hexahedron, the amorphous molded product may have a linear volumetric shrinkage of 5% or less.

In one preferred embodiment of the present invention, the amorphous molded article may have a crystallinity of 1% or less.

In one preferred embodiment of the present invention, the amorphous molded body may have a relative density of 50 to 70% relative to the glass theoretical density (3g / cm ³ ).

Another object of the present invention relates to a method for manufacturing a medicinal material for replacing the amorphous living hard tissue defects, step 1 of preparing a bioactive glass powder; Step 2 to produce a molded body by pressing the bioactive glass powder; And forming a amorphous molded body by heat-treating the molded body at a temperature below the glass transition temperature of the bioactive glass powder in the molded body. have.

In one preferred embodiment of the present invention, the bioactive glass powder of one step is melted by melting the mixture containing MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ at 1,350 ℃ ~ 1,600 ℃ Step 1-1 to prepare water; Quenching the melt to prepare glass; It may be prepared by performing a process including; steps 1-3 to powder the glass.

In a preferred embodiment of the present invention, the pressure forming in two steps may be performed through cold isostatic pressing (CIP).

As a preferred embodiment of the present invention, after preparing a mixture of the dispersant in the bioactive glass powder before the two-step pressure molding, the mixture may be molded by pressure molding.

As a preferred embodiment of the present invention, the mixture may contain 0.5 to 20 parts by weight of the dispersant based on 100 parts by weight of the bioactive glass powder.

In one preferred embodiment of the present invention, the dispersant is polyvinyl alcohol (PVA), polyvinylbutyl alcohol (PVB), polymethyl methacrylate (PMMA), polyethylene glycol (PEG), methyl cellulose, hydroxymethyl cellulose, It may include one or more selected from sodium carboxymethyl cellulose, paraffin, wax emulsion, microcrystalline wax and ethanol.

In a preferred embodiment of the present invention, the dispersant may further include water.

As a preferred embodiment of the present invention, the amorphous molded article of the three steps may be a variety of forms, such as block form, cylindrical form.

As a preferred embodiment of the present invention, the heat treatment in three steps may be performed by heat treatment the compression molding at 680 ℃ ~ 720 ℃.

Another object of the present invention relates to a method (method 1) of manufacturing artificial bone tissue using the non-crystalline biohard tissue defect replacement medicinal material, by processing the above-described medicinal material for replacing the non-crystalline biohard tissue defect part 1 step of manufacturing the workpiece; And firing the workpiece to prepare a fired product. 2 may be manufactured to produce artificial bone tissue.

As a preferred embodiment of the present invention, three stages of the slow cooling of the two-calcined product; may further include.

In one preferred embodiment of the present invention, the step 1 processing comprises the steps of generating the three-dimensional image information of the processing target bone tissue by photographing the processing target bone tissue; Identifying the processing target bone tissue based on the three-dimensional image information of the processing target bone tissue, and generating three-dimensional image information of at least one processing target bone tissue model corresponding to the processing target bone tissue; Verifying suitability of the at least one bone tissue model to be processed; In the verifying step, determining the three-dimensional image information of the processing target bone tissue model when there is no correction of the three-dimensional image information of the at least one processing target tissue model; In the verifying step, when there is correction information of the three-dimensional information of the at least one processing target bone tissue model, the three-dimensional image of the processing target bone tissue model by reflecting the correction information in the three-dimensional image information of the processing target bone tissue model Confirming the information; And processing the workpiece in the form of artificial bone tissue from the 3D image information of the determined bone tissue model to be processed.

As a preferred embodiment of the present invention, the two-step firing may be performed at 850 ° C to 1,200 ° C.

In one preferred embodiment of the present invention, the manufactured artificial bone tissue may include CaSiO 3.

In one preferred embodiment of the present invention, the prepared artificial bone tissue is Ca ₁₀ (PO ₄ ) ₆ A (where A is an oxygen atom). And Apatite containing at least one selected from Ca ₁₀ (PO ₄ ) ₆ B ₂ , wherein B is a hydroxyl group, a fluorine atom, or a chlorine atom; And Ca ₂ Mg (Si ₂ O ₇ ).

As a preferred embodiment of the present invention, the prepared artificial bone tissue may include CaSiO 3, the apatite and Ca ₂ Mg (Si ₂ O ₇ ) in a weight ratio of 1: 0.7 to 1.5: 0.5 to 1.2.

In one preferred embodiment of the present invention, the prepared artificial bone tissue is Ca ₁₀ (PO ₄ ) ₆ A (where A is an oxygen atom). And Apatite containing at least one selected from Ca ₁₀ (PO ₄ ) ₆ B ₂ , wherein B is a hydroxyl group, a fluorine atom, or a chlorine atom; Ca ₂ Mg (Si ₂ O ₇ ); And CaMgSi ₂ O ₆ ;

As a preferred embodiment of the present invention, the prepared artificial bone tissue CaSiO ₃ , the apatite and Ca ₂ Mg (Si ₂ O ₇ ) and CaMgSi ₂ O ₆ 0.7 ~ 1.3: 0.7 ~ 3.0: 0.5 ~ 1.2: 0.7 ~ 1.3 It may also be included in the weight ratio.

It is another object of the present invention to provide an artificial bone tissue prepared by using the method for replacing a non-crystalline bio-hard tissue defect portion prepared by using a bio-tissue defect replacement component composition.

In one preferred embodiment of the present invention, the artificial bone tissue may have a compressive strength of 900 ~ 1,600 Mpa.

As a preferred embodiment of the present invention, the artificial bone tissue may have a torsional strength of 0.6 N · m to 2.0 N · m.

As a preferred embodiment of the present invention, the artificial bone tissue may have a volume contraction rate of 5% or less based on the length of one axis of the shape of the hard tissue defect of the living body.

In a preferred embodiment of the present invention, the artificial bone tissue may have a relative density value of 95% or more of theoretical density.

As a preferred embodiment of the present invention, the artificial bone tissue may have bone fusion characteristics.

In one preferred embodiment of the present invention, the artificial bone tissue may include artificial bone, artificial joint, oral and maxillofacial bone, skull or dental artificial root.

As a preferred embodiment of the present invention, the artificial bone tissue may include a bone in the form of a spinal fusion disc, artificial bone for facial reconstruction, intervertebral spacer.

The non-crystalline biohard-tissue defect replacement medicinal material prepared using the bio-hard tissue defect replacement medicinal composition of the present invention can produce artificial bone tissue through a conventional etching process. In addition, the replacement material for the amorphous biohard tissue defect portion has a very low volume shrinkage rate, thereby minimizing the incompatibility of the artificial bone tissue manufactured using the same, thereby minimizing the defect rate, and the artificial bone tissue has excellent mechanical strength and biocompatibility. And adhesion with the implanted peripheral bone tissue (bone union properties) is very good.

1 is a schematic diagram of an embodiment of manufacturing the artificial bone tissue of the present invention.

2 is a schematic diagram of a manufacturing system that can be applied when manufacturing artificial bone tissue as one of the preferred embodiments of the present invention.

3 is a schematic diagram of a process of processing a medical material in the form of artificial bone tissue as one exemplary embodiment of the present invention.

Figure 4 is a photograph of the medicinal material for replacing the amorphous living hard tissue defects heat-treated at 800 ℃ in Example 1.

Figure 5 is a graph measuring the compressive strength of the sintered body according to the temperature carried out in Example 2.

6 is an X-ray diffraction pattern analysis result performed in Example 2. FIG.

7 is a result of measuring the apparent density and open porosity of Examples 1 to 3 and Comparative Examples 1 to 5 carried out in Experimental Example 2. FIG.

8A to 8E are XRD measurement results of Examples 1 to 3 and Comparative Examples 4 to 5 carried out in Experimental Example 3, and FIG. 8F is qualitative analysis measurement data by X-ray diffraction method of Example 1. FIG.

FIG. 9 is an electron microscope measurement photograph of each of the surfaces of Examples 1 to 3 carried out in Experimental Example 4. FIG.

10A is a result of measuring bioactivity of each of the sintered bodies of Examples 1 to 3 performed in Experimental Example 5, and FIG. 10B is a result of cytotoxicity evaluation experiment.

11A to 11C are the results of the biocompatibility visual inspection of each of the sintered bodies of Examples 1 to 2 and Comparative Example 7 carried out in Experimental Example 7. FIG.

12A to 12C are each a radiological test result of each of the sintered bodies of Examples 1 to 2 and Comparative Example 7 carried out in Experimental Example 7.

13A to 13C are the results of histological examination of each of the sintered bodies of Examples 1 to 2 and Comparative Example 7 carried out in Experimental Example 7. FIG.

FIG. 14 shows a model of the disk carried out in Preparation Example 1. FIG.

15 is a picture of the artificial bone tissue in the form of a disk prepared in Preparation Example 1.

Figure 16 shows the modeling of the spine performed in Preparation Example 2.

17A and 17B are photographs of artificial bone tissue in the form of shaped bodies and vertebrae prepared in Preparation Example 2. FIG.

Figure 18 is a picture taken of the artificial bone tissue of the spinal form prepared in Preparation Example 2 in accordance with the 3D printing prototype.

Hereinafter, the present invention will be described in more detail.

As used herein, the term "bioactive glass powder" refers to a powder composed of components in which apatite is produced upon high temperature firing and exhibits bioactivity during transplantation.

The term " amorphous " such as amorphous biohard tissue defects of the present invention, amorphous shaped bodies, etc. does not mean that the crystallinity is 0%, but that the crystallinity is 1% or less.

The term "compressive strength" of the present invention may mean the maximum stress of a material that can withstand under compressive load. The compressive strength of a material broken into fragments during compression can be defined in the agreement as an independent property, but the compressive strength of materials that do not break into compression can be defined as the amount of stress required to distort any amount of material. have. The force applied in the test instrument can be measured by plotting it against deformation. In the compression test, the compressive strength can be calculated by dividing the maximum load by the initial cross section of the specimen.

The term "torsional strength or torsion" of the present invention refers to the ability of the material to withstand torsional loads, the torsional strength is the maximum strength of the material affected by the torsional load, it can hold the material before fracture Maximum torsional stress may be present. It is also called wave step number or shear strength. The unit of measurement may be Newton meters (N · m) or feet-pound force (ft · lbf).

The term "fatigue strength" of the present invention refers to the magnitude of the fluctuating stress required to break a fatigue test specimen by applying a predetermined number of repetitive loads, wherein the repeated number of times is referred to as fatigue life. do. Fatigue strength can generally be measured directly from the S-N diagram, but is not limited thereto. ASTM defines fatigue strength, SNf, as the stress value at which Nf cycle number breaks occur.

The biomaterial for replacing the amorphous biohard tissue defect of the present invention is a biomaterial for replacing the amorphous biohard tissue defect prepared using a bioactive glass powder, comprising: preparing a bioactive glass powder; Step 2 to produce a molded body by pressing the bioactive glass powder; A step 3 of manufacturing the amorphous molded body by heat-treating the molded body at a temperature below the glass transition temperature of the bioactive glass powder in the molded body; And by firing the amorphous molded body to produce a fired body can be prepared by performing a process comprising a.

In the method of manufacturing a substitute for the amorphous biohard tissue defect of the present invention, the bioactive glass powder in one step may include SiO ₂ and CaO, preferably SiO ₂ 40 ~ 75 mol%, CaO 25 ~ It may also contain trace amounts of 60 mol% and other unavoidable impurities. In addition, the bioactive glass powder may further include one or more components selected from P ₂ O ₅ , MgO, Na ₂ O, B ₂ O ₃ and CaF ₂ as other components in addition to SiO ₂ and CaO.

In more detail, a method for preparing a bioactive glass powder in one step is described. 1- to prepare a melt by melting a mixture including MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ . Stage 1; A step 1-2 of preparing a glass prepared by quenching the melt; And it may be prepared by performing a process comprising; steps 1-3 to powder the glass.

In addition, the mixture of step 1-1 is a mixture of MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ , preferably MgO 4.5 ~ 6.5 wt%, CaO in the total weight of the mixture 41-43 wt%, SiO ₂ 34 to 36.2 wt%, P ₂ O ₅ 13.5-17 wt%, CaF ₂ 0.9-2.5 wt% and B ₂ O ₃ 0.2-1.5 wt%, more preferably MgO 5.2-6.5 wt%, CaO 41.0-42.3 wt%, SiO ₂ 35.3 to 36.2 wt%, P ₂ O ₅ 13.5-15.0 wt%, CaF ₂ 0.97-2.2 wt% and B ₂ O ₃ 0.2 to 1.5 wt%, more preferably MgO 5.50 to 6.35 wt%, SiO ₂ 35.3 to 36.2 wt%, P ₂ O ₅ 13.5 to 14.6 wt%, CaF ₂ 1.6 to 2.2 wt% and B ₂ O ₃ 0.2 to 1.0% by weight and the balance of CaO (mixture 1).

In this case, when the MgO content is less than 4.5% by weight, there may be a problem in that mechanical properties such as compressive strength are reduced, and when the MgO content is higher than 6.5% by weight, the sintering property may be inferior. When the CaO content is less than 41 wt%, there may be a problem that the density of the glass powder is low and the porosity is high, and when the CaO content is more than 43 wt%, there may be a problem that the sintering property is lowered. In addition, SiO ₂ If the content is less than 34% by weight, there may be a problem that the sintering property is lowered, and when the content is more than 36.2% by weight, the sintering property may be excellent but the bending strength may be lowered.

If the P ₂ O ₅ content is less than 13.5% by weight, there may be disadvantageous problems in terms of bioactivity. If the P ₂ O ₅ content is more than 17% by weight, it may be advantageous in terms of bioactivity. There may be a problem that the physical properties are lowered. In addition, when the CaF ₂ content is less than 0.9% by weight, there may be a problem that the mechanical properties are reduced, and when the CaF ₂ content is more than 2.5% by weight, other components may be relatively reduced, which may cause other problems. And B ₂ O ₃ If the content is less than 0.2% by weight, there may be a problem that the sintering temperature is higher, and if the content exceeds 1.5% by weight, there may be a problem that hinders densification.

In addition, the mixture of step 1-1, unlike the mixture 1, the compression strength and bending strength of the glass powder is lower than the mechanical properties, but in the case of preparing a glass powder having a relatively higher biocompatibility than the mixture 1, The mixture is MgO 4.5-6.5 wt%, CaO 41-43 wt%, SiO ₂ 30.5 to 32.5 wt%, P ₂ O ₅ 18.5 to 19.8 wt%, CaF ₂ 0.5 to 1.5 wt% and B ₂ O ₃ 0.2 to 1.5% by weight, preferably MgO 4.5 to 6.5% by weight, CaO 41 to 43% by weight, SiO ₂ 30.8 to 32.2 wt%, P ₂ O ₅ 18.5 to 19.3 wt%, CaF ₂ 0.6 to 1.2 wt% and B ₂ O ₃ 0.2 to 1.5% by weight (mixture 2).

Examples of the components of the more specific bioactive glass powder of the present invention are shown in Table 11 below.

division	Bioactive Glass Powder Composition
Embodiment 1 (mixture 1)	MgO 5.70-6.10 wt%, SiO 2 35.50 to 36.10 weight percent, P 2 O 5 13.70 to 14.80 wt%, CaF 2 1.60 to 2.20 wt%, B 2 O 3 0.4 to 0.7 wt% and balance of CaO
Embodiment 2 (mixture 1)	MgO 5.97 wt%, CaO 41.79 wt%, SiO 2 35.82 weight percent, P 2 O 5 13.93 wt%, 1.99 wt% CaF 2 and B 2 O 3 0.5 wt%
Embodiment 3 (mixture 1)	MgO 4.90-5.18 wt%, SiO 2 34.0 to 35.2 weight percent, P 2 O 5 15.0 to 16.3 wt%, CaF 2 0.70 to 1.50 wt%, B 2 O 3 0.4 to 0.7 wt% and balance of CaO
Embodiment 4 (mixture 1)	MgO 4.975 wt%, CaO 42.785 wt%, SiO 2 34.825 weight percent, P 2 O 5 15.92 wt%, CaF 2 0.995 wt%, B 2 O 3 0.5 wt%
Embodiment 5 (mixture 2)	MgO 4.9-6.3 wt%, SiO 2 31.0 to 32.0 weight percent, P 2 O 5 18.6 to 19.0 wt%, CaF 2 0.75 to 1.10 wt%, B 2 O 3 0.3 to 1.0 wt% and balance of CaO
Embodiment 6 (mixture 2)	MgO 5.97 wt%, CaO 41.79 wt%, SiO 2 31.84 weight%, P 2 O 5 18.905 wt%, CaF 2 0.995 wt%, B 2 O 3 0.5 wt%

In addition, the mixture of step 1-1 is MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ depending on the purpose of use In addition, Na ₂ O may be further included.

In addition, the melting of the step 1-1 is preferably performed at 1,350 ° C. to 1,600 ° C., preferably at 1,450 ° C. to 1,550 ° C., and when the melting temperature is less than 1,350 ° C., it is heated to a melting point or more. There may be a problem that can not be sufficiently melted, and if the heat treatment temperature exceeds 1,600 ℃ there may be a problem that is accompanied by waste of energy due to unnecessary heating, it is preferable to perform the melting at the temperature.

Next, a 1-3 step process of pulverizing the glass prepared by quenching in 1-2 steps is carried out, in this case, the grinding method is not particularly limited, a general grinding method used in the art can be used.

The bioactive glass powder prepared by pulverization may have an average particle diameter of 0.5 μm to 10 μm, and preferably has an average particle diameter of about 0.5 μm to 5 μm, more preferably about 1.8 μm to 5 μm.

In this way, the composition of the medicinal material can be adjusted according to the characteristics of the biological hard tissue defects to be applied by changing the components and the ratio of the bioactive glass powder.

Next, with reference to step 2, the amorphous molded body can be prepared by the general pressure molding method used in the art of the bioactive glass powder of step 1 prepared by the above method, preferably cold isotropic compression (cold isostatic pressing; CIP) can be used. The molded article obtained in the second step may have various shapes such as a block shape and a cylindrical shape.

In addition, by using bioactive glass powder alone or mixed with a dispersant before pressure molding in step 2, the bioactive glass powder in the molded body is uniformly distributed and evenly mixed, thereby resulting in amorphous biohard tissue defects having uniform physical properties. Alternative medicinal materials may also be prepared. When using a dispersant, the dispersant may be used in an amount of 0.5 to 20 parts by weight, preferably 0.5 to 10 parts by weight, based on 100 parts by weight of the bioactive glass powder.

In addition, as the dispersant, polyvinyl alcohol (PVA), polyvinylbutyl alcohol (PVB), polymethyl methacrylate (PMMA), polyethylene glycol (PEG), methyl cellulose, hydroxymethyl cellulose, sodium carboxymethyl cellulose, paraffin , Wax emulsions, microcrystalline waxes and ethanol selected from single or two or more kinds can be mixed and used.

The dispersant may be a dispersion solution in which the dispersant such as PVA and PVB is dispersed in a solution such as water.

Next, in the preparation of the medicinal material for replacing the amorphous biohard tissue defect, the third step is to form the molded article of the second step at 680 ℃ ~ 720 ℃, preferably 685 ℃ ~ 715 ℃, more preferably 690 ℃ ~ 710 ℃ As a step of producing an amorphous molded body by heat treatment at, the heat treatment should be able to achieve a level of strength capable of processing the bioactive glass molded body. At this time, since the densification of the molded body does not proceed at a heat treatment temperature of less than 680 ℃, it may be easily damaged after processing, heat treatment at the temperature above 720 ℃ because the molded body is rapidly contracted and the strength and hardness may be increased and processing may be impossible. It is preferable to

The amorphous molded article prepared by heat treatment in this way (ie, a substitute for amorphous biohard tissue defects) may have a linear volumetric shrinkage of 5% or less, preferably 1% to 4.5% when the cube is heat treated at 700 ° C. It may be more preferably 1% to 4%. By having such a very low linear volumetric shrinkage rate, the individual customized processing (processing according to design design and design) and processing treatment to apply the medicinal material for replacing the amorphous biohard tissue defect of the present invention to artificial artificial bone tissue, etc. It is possible to minimize the deformation of the shape after firing the medicinal material.

In addition, the amorphous molded body may have a degree of crystallinity of 1% or less, and may have a relative density of 50 to 70% with respect to glass theoretical density (3 g / cm ³ ), and thus may be easily processed into a desired shape.

The medicinal material for replacing the amorphous living hard tissue defect prepared by the method described above may be manufactured and processed by the following method to prepare artificial bone tissue.

A method for performing the process shown in the schematic diagram of FIG. 1, comprising: a step of manufacturing a workpiece by processing a medicinal material for replacing an amorphous living hard tissue defect; And firing the workpiece to prepare a fired product. 2 may be manufactured to produce artificial bone tissue.

And, the third step of the slow cooling of the fired product of two steps; may further include.

Step 1 is a process of processing the medical material in the form of artificial bone tissue to be prepared, it can be carried out by the method shown in a schematic diagram in Figure 3, specifically, by photographing the processing target bone tissue 3 Generating dimensional image information; Identifying the processing target bone tissue based on the three-dimensional image information of the processing target bone tissue, and generating three-dimensional image information of at least one processing target bone tissue model corresponding to the processing target bone tissue; Verifying suitability of the at least one bone tissue model to be processed; In the verifying step, when there is no correction of the 3D image information of the at least one processing target bone tissue model, determining 3D image information of the processing target bone tissue model; In the verifying step, when there is correction information of the three-dimensional information of the at least one processing target bone tissue model, the three-dimensional image of the processing target bone tissue model by reflecting the correction information in the three-dimensional image information of the processing target bone tissue model Confirming the information; And processing the workpiece in the form of artificial bone tissue from the 3D image information of the determined bone tissue model to be processed.

In generating the 3D image information of the bone tissue model to be processed, the 3D image information of the bone tissue to be processed is referred to at least one or more additional information of identification information, a disease name, and a surgical method of the bone tissue to be processed. 3D image information of the bone tissue model to be processed may be generated. In generating the 3D image information of the bone tissue model to be processed, the first data storing basic image information including image information of normal bone tissue collected from human bodies by age, gender, height, weight, or race A base may be provided, and detecting the 3D image information of the bone tissue model to be processed may be performed from the basic image information.

The first database further stores additional identification information about the normal bone tissue, a related disease name, or a surgical method, and the image information of the normal bone tissue is modified by referring to the surgical method to determine the target bone tissue model. 3D image information may also be generated. A second database may be provided in which information on at least one of the shape, material, microstructure, strength, surgical method, and surgical success rate of the artificial bone tissue is stored.

In addition, the verifying may be performed by simulating 3D image information of the therapeutic bone tissue model according to a surgical method by editing, comparing, or measuring a graphic object implemented from 3D image information. .

The determining of the 3D image information of the bone tissue model to be processed may further include performing learning by replacing 3D image information of the normal bone tissue with 3D image information of the replacement bone tissue.

And, the processing of the first step can be processed using the artificial bone tissue manufacturing system 100 as follows (see Fig. 2).

 The artificial bone tissue manufacturing system acquires the image information of the bone tissue to be processed from the imaging unit 111 which photographs a target bone tissue of the patient to generate 3D image information, and is coupled to a network for transmitting the image information. A client computer 112 comprising a user interface for input of a user or output of information; Based on the image information of the processing target bone tissue received from the client computer, identifying the processing target bone tissue and generates three-dimensional image information of at least one therapeutic bone tissue model corresponding to the processing target bone tissue, the client A server computer (121) for transmitting three-dimensional image information of the at least one processing target bone tissue model to the client computer so that the image information of the at least one processing target bone tissue model is verified and confirmed by a computer; And a processing unit 122 for manufacturing a workpiece in the form of an artificial bone tissue based on the 3D image information of the bone tissue model for processing target determined from the server computer.

The imaging unit 111 and the client computer 112 may be installed in an operating room or a diagnostic room in the hospital system 110, and the server computer 121 and the processing unit 122 may be located at a separate place from the operating room or the diagnostic room. It may be installed in the artificial bone tissue processing and manufacturing system 120 is disposed. Each component may allow remote access to each other through the network 130, as shown in FIG. To this end, client computer 112 or server computer 121 may include a communication interface (not shown) for connecting to network 130.

In one embodiment, there are a plurality of hospital systems 110, and thus, a plurality of client computers 112 and imaging units 111, and the artificial bone tissue processing and manufacturing system 120 may be a single. In this case, a many-to-one relationship may be established between the plurality of hospital systems 110 and one artificial bone tissue processing and manufacturing system 120. The plurality of client computers and one server computer may be communicatively connected to each other through a network 130 including a wired and wireless communication network.

In addition, the imaging unit is an imaging device capable of generating any three-dimensional image information including information on the size, shape, location or disease of the bone tissue to be processed, an x-ray device, computed tomography or computerized and at least one of an axial tomography (MRI) device, a magnetic resonance imaging (MRI) device, an optical coherence tomography device, an ultrasound imaging device, and a positron emission tomography (PET) device. Since the 3D image information may be generated by 3D rendering from a plurality of 2D information, the imaging unit 111 may include an imaging device capable of generating 2D image information capable of 3D rendering. The 3D image information may include 3D image information of the processed target bone tissue for replacement, prosthesis, reconstruction, or fusion for the treatment of the processed target bone tissue. Optionally, the apparatus may further include three-dimensional image information about wound bed preparation of bone tissue and image information about adjacent bone tissue, muscle tissue, nerve tissue, or vascular tissue according to a surgical method. These are collectively referred to as three-dimensional image information of the bone tissue to be processed.

The client computer 112 provides the server computer with the image information of the bone tissue to be processed, and additional information of at least one or more of identification information of the bone tissue to be processed, a disease name, and a surgical method. The server computer may generate three-dimensional image information of the processing target bone tissue model with reference to the additional information together with the image information. The server computer includes a first database storing basic image information including image information of normal bone tissue collected from human bodies by age, gender, height, weight, or race, and the server computer includes the basic image. The 3D image information of the therapeutic bone tissue model may be generated from the information.

The client computer 112 or server computer 121 is a permanent storage device or temporary storage device for storing application software and data, at least one or more databases stored in the permanent storage device or temporary storage device, and controlling them. It may include a central processing unit for. As an example of the database, first and second databases 123 and 124 provided on the server computer 121 side are illustrated. The client computer 112 or server computer 121 also has a user interface including inputs such as a mouse, keyboard or touch panel, and outputs such as a monitor, projection display and head-up display. The user interface may implement augmented reality in order to improve the reality and information transfer efficiency of a simulation to be described later. Reference numeral 113 in FIG. 2 shows the user interface coupled to the client computer 112.

In an embodiment, the user interface 113 of the client computer 112 may be shared remotely by the server 121. For example, when the user interface 113 is a display, the contents operated by the user of the client computer 112 side are transmitted to the user of the server 121 side, and the user interface 113 is displayed through the display of the server side 121. The same picture content embodied in can be displayed. Similarly, the contents operated by the user of the server 121 may be implemented in the user interface 113. The implementation manner thereof may be realized through streaming of multimedia information or transmission and reception of control information using the Internet, but the present invention is not limited thereto.

The first database may further include identification information of the normal bone tissue, a name of a related disease, or information about a surgical method, and the first database may include an image of the patient's past target bone tissue. Information or image information about the other normal bone tissue in the left-right symmetry relationship of the bone tissue to be processed may be further included.

The client computer may transmit the image information of the bone tissue to be processed to a server computer, and the server computer may generate 3D image information of the bone tissue model to be processed by modifying image information of normal bone tissue. The server computer may include a second database in which information on at least one of the shape, material, microstructure, and strength of the artificial bone tissue is stored.

In addition, as an embodiment, the client computer may edit, compare, or measure a graphic object through which the user may simulate three-dimensional image information of the processed bone tissue model provided from the server computer according to a surgical method. Measurement can also be performed. In addition, the user may determine the processing target bone tissue model by accepting or modifying the processing target bone tissue model transmitted from the server computer through the simulation result. To this end, the client computer may include at least one of an editing tool, a comparison tool, and a dimensional measurement tool of a graphic object for performing the simulation.

The user input may include a command received from a user using at least one of an editing tool, a comparison tool, or a dimension measuring tool of a graphic object to modify 3D image information of a target tissue model.

The three-dimensional image information of the confirmed artificial bone tissue may be stored in any digital format decodable by the processing unit 122 described later, or by way of non-limiting example, Autocad ^TM , Catia ^TM , Solidworks ^TM ) Can be stored in the database 124 in a digital format of three-dimensional image information that can be supported by commercial software such as MIMICSTM, or 3D MAXTM.

The processing unit 122 receives artificial bone tissue image information stored in the second database 124 of the server computer 121 and optionally additional information such as material and strength of the artificial bone tissue, and based on this, the three-dimensional shape It can be processed into workpieces in the form of artificial bone tissue. For example, the processing unit 122 may process the workpiece by relatively moving the machining tool and the table in three dimensions based on the image information or additional information. At this time, the processing may be performed by a milling method using a commercial milling machine. If necessary, in order to utilize various curved surfaces of the workpiece, a CNC milling machine, a 4-axis milling machine, a 5-axis milling machine, or a dental prosthesis processing machine, etc. capable of multi-axis machining may be used. In another embodiment, the processing unit 122 may manufacture a workpiece (artificial bone tissue) 125 using a mold.

Next, step 2 is a step of firing the workpiece processed in the form of artificial bone tissue to be prepared in step 1, firing is a step of forming a high-strength bioactive crystallized glass material by sintering by heat treatment at a high temperature.

In the present invention, the firing may be performed by firing a processed product by using the primary heat treated medicinal material for replacing the amorphous biotissue defect, wherein the shrinkage during heat treatment may be controlled by an isotropic shrinkage, and the shrinkage rate of the sintered material is respectively It can be made almost identical to the error range within 5% of the length of the axial direction.

The two-stage firing is performed at 850 ° C. to 1,200 ° C., and when firing is performed at less than 850 ° C., the glass transition temperature of SiO ₂ , the main component of the bioactive glass powder included in the workpiece, is approximately 800 ° C. Serious breakage may occur.

In addition, the firing temperature affects the compressive strength of the sintered product. When the firing temperature is sintered and sintered at 1,000 ° C., the sintering temperature shows a compressive strength of 1,300 Mpa or more, and exhibits high mechanical properties (FIG. 5). ).

Next, the third step is to sinter the sintered plastics, and the sintered materials are rapidly shrunk and densified as the liquid phase sinters as the glass transition temperature progresses. If the thermal shocks occur in the plastics, serious damage may occur. have. Therefore, the temperature should be lowered slowly so that there is no thermal shock. When the slow cooling rate is 5 ° C / min, since the breakage of the molded body occurs seriously, slow cooling at a slower speed, it is preferable to perform the slow cooling at 2 ° C / min.

Artificial bone tissue prepared by the above method may be 15 to 25%, preferably 16 to 20%, more preferably 17 to 19% based on the length of the uniaxial direction. And, the volume shrinkage of the fired product may be 30 to 55%, preferably 40 to 50%.

In addition, the artificial bone tissue of the present invention may include CaSiO ₃ .

In addition, the artificial bone tissue of the present invention CaSiO ₃ ; Ca ₁₀ (PO ₄ ) ₆ A (where A is an oxygen atom) And Apatite containing at least one selected from Ca ₁₀ (PO ₄ ) ₆ B ₂ , wherein B is a hydroxyl group, a fluorine atom, or a chlorine atom; And Ca ₂ Mg (Si ₂ O ₇ ); and preferably include CaSiO ₃ , the apatite and Ca ₂ Mg (Si ₂ O ₇ ) in a weight ratio of 1: 0.7 to 1.5: 0.5 to 1.2. It may be.

In addition, the artificial bone tissue of the present invention CaSiO ₃ ; Ca ₁₀ (PO ₄ ) ₆ A (where A is an oxygen atom) And Apatite containing at least one selected from Ca ₁₀ (PO ₄ ) ₆ B ₂ , wherein B is a hydroxyl group, a fluorine atom, or a chlorine atom; Ca ₂ Mg (Si ₂ O ₇ ); And CaMgSi ₂ O ₆ ; Preferably, CaSiO ₃ , the apatite and Ca ₂ Mg (Si ₂ O ₇ ) and CaMgSi ₂ O ₆ are 0.7-1.3: 0.7-3.0: 0.5-1.2: 0.7 It may be included in a weight ratio of ~ 1.3, more preferably CaSiO ₃ , the apatite and Ca ₂ Mg (Si ₂ O ₇ ) and CaMgSi ₂ O ₆ 1: 1: 0.7 to 3.0: 0.5 to 1.2: 0.7 to 1.3 by weight You may.

Artificial bone tissue of the present invention (or a plastic material for replacing the amorphous biohard tissue defects) may have a compressive strength of 900 to 1,600 Mpa, preferably 980 to 1,500 Mpa, more preferably 1,200 to 1,480 Mpa. .

In addition, the artificial bone tissue of the present invention (or a plastic product of a substitute for the amorphous biohard tissue defect) has a bending strength of 150 to 300 Mpa, preferably 220 to 300 Mpa, more preferably 245 to 285 Mpa. Can be.

In addition, the artificial bone tissue of the present invention (or a fired product of a substitute for amorphous biohard tissue defect) may have a fracture toughness value of 2 Mpa · m ^1/2 or more.

The artificial bone tissue of the present invention (or a fired product of a substitute for amorphous living hard tissue defects) may have a torsional strength of 0.6 N · m to 2.0 N · m, preferably 0.6 N · m to 1.5 N · m. In addition, it is possible to have a fatigue strength equal to or more than the maximum compressive strength, which does not break even after repeating 5 million cycles at a repetition speed of 5 Hz and a stress ratio of 10.

The artificial bone tissue may have a volume shrinkage of 5% or less based on the length of one axis of the shape of the hard tissue defect of the living body, and the artificial bone tissue may have a relative density value of 95% or more of theoretical density.

In addition, the artificial bone tissue of the present invention may have a change in the apparent density and the open porosity, depending on the firing temperature of the two stages, the artificial bone tissue (sintered body) is 2.95 ~ 3.05 g / cm ³ when firing at 850 ℃ , Open porosity is 0.90% ~ 1.20%, the apparent density during firing at 900 ℃ is 2.95 ~ 3.05 g / cm ³ , the open porosity may be 0.55% ~ 1.20%. In addition, the artificial bone tissue (sintered body) has an apparent density of 2.97 to 3.07 g / cm ³ when fired at 950 ° C., an open porosity of 0.46% to 1.00%, and a density of 2.99 to 3.08 g / cm ³ when fired at 1,000 ° C. The porosity may be 0.50% to 1.00%. In addition, the artificial bone tissue (sintered body) may have an apparent density of 2.97 to 3.10 g / cm ³ when fired at 1,050 ° C, and an open porosity of 0.50% to 2.75%, preferably 0.50 to 0.95%.

In addition, the artificial bone tissue of the present invention can exhibit a bone fusion (bone fusion) characteristics can also effectively replace the hard tissue defects of the living body when implanted in vivo.

Specifically, the artificial bone tissue according to the present invention may be artificial bone, artificial joint, oral and maxillofacial bone, skull or dental artificial tooth. More specifically, for example, the artificial bone tissue of the present invention can be applied as an artificial bone in the form of a disc for spinal fusion, artificial bone for facial reconstruction, intervertebral spacer, and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the following Examples are not intended to limit the scope of the present invention, which should be construed as to help the understanding of the present invention.

[ Example ]

Preparation  One : Bioactivity  Manufacture of glass powder

5.97 wt% MgO powder, 41.79 wt% CaO powder, 35.82 wt% SiO ₂ powder, 13.93 wt% P ₂ O ₅ powder, 1.99 wt% CaF ₂ powder and B ₂ O ₃ The mixture was prepared by mixing and stirring 0.5% by weight.

Next, the mixture was heat-treated at 1,550 ° C., quenched and vitrified, and then pulverized and powdered to an average particle size of 1.8 μm, thereby preparing a bioactive glass powder.

Preparation  2 to 3 and Comparative Preparation  1 to 5

To prepare a bioactive glass powder in the same manner as in Preparation Example 1, to prepare a mixture to have a composition as shown in Table 1 to prepare a bioactive glass powder.

Division (% by weight)	MgO	CaO	SiO 2	P 2 O 5	CaF 2	B 2 O 3
Preparation Example 1	5.97	41.79	35.82	13.93	1.99	0.5
Preparation Example 2	4.975	42.785	34.825	15.92	0.995	0.5
Preparation Example 3	5.97	41.79	31.84	18.905	0.995	0.5
Comparative Preparation Example 1	4.975	43.78	33.83	17.91	0.995	0.5
Comparative Preparation Example 2	4.975	42.785	32.835	17.91	0.995	0.5
Comparative Preparation Example 3	5.97	40.795	31.84	18.905	1.99	0.5
Comparative Preparation Example 4	4.975	43.78	35.82	13.93	0.995	0.5
Comparative Preparation Example 5	5.97	40.795	35.82	13.93	1.99	0.5

Example  1: amorphous living body Hard tissue defect  Alternative Medical supplies  According to manufacturing and heat treatment temperature Shrinkage  Research

10 parts by weight of a dispersant (10% by volume polyvinyl alcohol and 90% by volume water) was mixed with respect to 100 parts by weight of the bioactive glass powder prepared in Preparation Example 1, to prepare a medicinal composition for replacing the amorphous biological hard tissue defect. .

Next, a block-shaped molded body was prepared by isotropically compressing the medicinal composition for replacing the amorphous living hard tissue defect by cold isostaticpressing (CIP).

The molded article was heat-treated at 650 ° C., 700 ° C., 750 ° C. and 800 ° C., respectively, and the shrinkage ratios of the sides according to the respective heat treatment temperatures were examined. As a result, the results of heat treatment at 700 ° C. and 750 ° C. It is shown in Table 2 below. At 600 ° C., a temperature condition of less than 650 ° C., the compaction of the molded body did not proceed and was easily broken after processing. In addition, when sintering at 800 ℃ it was confirmed that the product breakage occurs due to the interruption of crystallization (see Fig. 4).

[Revisions under Rule 91 21.12.2017]

When the heat treatment at 750 ℃ through the measurement results of Table 2 it can be confirmed that the molded body is shrunk sharply, through which the strength and hardness of the molded body can be seen that the processing is impossible. On the contrary, when the heat treatment was performed at 700 ° C., the molded body was shrunk to about 5% and the linear shrinkage was about 2%.

Experimental Example  1: Preparation of Sintered Sintered Body and Depending on Firing Temperature Shrinkage

Firing temperature of 750 ℃, 850 ℃, 900 ℃ and 1,000 ℃ of the block-shaped amorphous molded body (medical material for replacing the amorphous living hard tissue defects) prepared by the heat treatment at 700 ℃ prepared in Example 1 without additional processing After sintering at to prepare a sintered compact to evaluate the compressive strength, the results are shown in FIG.

Referring to FIG. 5, the compressive strength of 145 Mpa or more was exhibited from 750 ° C. showing rapid contraction, and the increase was sharply increased with increasing firing temperature. From the firing temperature 920 ~ 940 ℃ showed a compressive strength of more than 900 Mpa, in particular, when the firing temperature is 1,000 ℃ it was confirmed that the excellent mechanical properties were maintained by showing a compressive strength of 1,300 Mpa or more. Through this, it was confirmed that the proper firing temperature is 850 ℃ ~ 1,200 ℃.

And, the shrinkage of each side of the sintered body prepared by firing at 1,000 ℃ was measured, which is shown in Table 3 below.

[Revisions under Rule 91 21.12.2017]

Through the above Table 3, when the molded body heat-treated at 700 ℃ at 1,000 ℃ it can be confirmed that the shrinkage of about 18% uniformly contracted in the horizontal, vertical, height direction.

And the result of X-ray diffraction pattern analysis of the manufactured sintered compact is shown in FIG.

Specifically, 2θ, the major line of each material, is 29.5 to 30.5 ° for CaSiO ₃ (wollastonite), 31.5 ° to 32.5 ° for Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (hydroxyapatite), and Ca ₂ Mg (Si ₂ O ₇ ) (acmanite) was found to be in the range of 30.5 ° ~ 31.5 ° and CaMgSi ₂ O ₆ (diopside) in the range of 29.5 ° ~ 30.5 °.

Example  2 to 3 and Comparative example  1 to 5: amorphous living body Hard tissue defect  Alternative Medical supplies  And objections Plastic  Produce

Prepare molded bodies heat-treated at 700 ° C. in the same manner as in Example 1, except for using the bioactive glass powders of Preparation Examples 2 to 3 and Comparative Preparation Examples 1 to 5 instead of the bioactive glass powders of Preparation Example 1, respectively. Examples 2 to 3 and Comparative Examples 1 to 5 were carried out by manufacturing the medicinal materials (or amorphous molded bodies) for replacing the living hard tissue defects, respectively (see Table 4 below).

In addition, each of the medicinal materials for replacing the amorphous living hard tissue defects (Examples 1 to 3 and Comparative Examples 1 to 5) were respectively processed at 750 ° C, 800 ° C, 850 ° C, 900 ° C, 950 ° C, 1,000 ° C, and 1,050 without additional processing. It was calcined at 2 ° C. for 2 hours to prepare sintered bodies which were fired products.

Comparative example  6

SiO ₂ The powder, the hydroxyapatite powder, and the mixed powder of Ca (OH) ₂ powder were heat-treated at 1550 ° C., quenched and vitrified, and then pulverized to a powder having an average particle diameter of 1.8 μm, thereby preparing a bioactive glass powder. Thereafter, the molded body obtained by heating the composition of 100 parts by weight of the bioactive glass powder and 10 parts by weight of the dispersant (10% by volume polyvinyl alcohol and 90% by volume water) at 700 ° C in the same manner as in Example 2 was used at 1,050 ° C for 2 hours. Calcined to include CaSiO ₃ and Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ A sintered body that was a fired product was produced.

Comparative example  7

Using a composition containing 100% by weight of hydroxyapatite, a molded body heat-treated at 700 ° C in the same manner as in Comparative Example 6 was fired at 1,300 ° C for 2 hours to prepare a sintered body.

Substances for replacing amorphous living hard tissue defects	Bioactive Glass Powder	Heat treatment temperature	Firing temperature
Example 1	Preparation Example 1	700 ℃	1050 ℃
Example 2	Preparation Example 2	700 ℃	1050 ℃
Example 3	Preparation Example 3	700 ℃	1050 ℃
Comparative Example 1	Comparative Preparation Example 1	700 ℃	1050 ℃
Comparative Example 2	Comparative Preparation Example 2	700 ℃	1050 ℃
Comparative Example 3	Comparative Preparation Example 3	700 ℃	1050 ℃
Comparative Example 4	Comparative Preparation Example 4	700 ℃	1050 ℃
Comparative Example 5	Comparative Preparation Example 5	700 ℃	1050 ℃

Experimental Example  2: apparent density of sintered body and Open porosity  Measurement experiment

Apparent density (g / cm ³ ) and open porosity (%) were measured according to the firing temperature of the sintered bodies prepared in Examples 1 to 3 and Comparative Examples 1 to 5, and the results are shown in the following table. 5 to Table 6 and shown in FIG.

Classification (apparent density, g / cm 3 )	750 ℃	800 ℃	850 ℃	900 ℃	950 ℃	1,000 ℃	1,050 ℃
Example 1	2.96	2.97	2.98	2.98	3.00	3.04	3.05
Example 2	2.96	2.97	2.97	3.00	3.00	3.00	3.02
Example 3	2.90	2.98	2.99	3.00	3.03	3.04	2.97
Comparative Example 1	2.40	2.49	2.48	2.49	2.50	2.49	2.45
Comparative Example 2	2.63	2.67	2.68	2.69	2.70	2.71	2.69
Comparative Example 3	2.30	2.46	2.48	2.49	2.52	2.52	2.36
Comparative Example 4	2.93	2.94	2.95	2.95	2.97	3.00	3.00
Comparative Example 5	2.87	2.87	2.89	2.89	2.91	2.96	2.95

Classification (Open Porosity,%)	750 ℃	800 ℃	850 ℃	900 ℃	950 ℃	1,000 ℃	1,050 ℃
Example 1	0.87	0.87	0.97	1.07	0.97	0.97	0.58
Example 2	1.17	0.38	1.17	0.58	0.49	0.78	0.88
Example 3	3.80	1.80	1.07	1.17	0.80	0.60	2.63
Comparative Example 1	19.6	16.6	17.2	16.7	16.8	17.4	18.9
Comparative Example 2	12.4	11.0	10.7	11.2	10.6	10.7	11.5
Comparative Example 3	24.0	19.0	19.2	19.2	18.5	19.4	23.8
Comparative Example 4	0.78	0.88	0.49	0.97	1.17	0.78	0.58
Comparative Example 5	1.90	1.57	1.86	2.44	1.86	1.95	1.46

Referring to Tables 5 to 6 and FIG. 7, in the case of Comparative Examples 1 and _{2 in which the} P ₂ O ₅ content is more than 17 wt%, and in Comparative Example 3 in which the CaO content is less than 41 wt%, the apparent density Tends to be low and / or high open porosity.

On the contrary, in Example 3, even though 18.905 wt% of P ₂ O ₅ content exceeded 17 wt%, a high density and low porosity were observed. It is believed to be due to the difference in CaO and CaF ₂ content.

Experimental Example  3: of sintered body XRD  analysis

(1) XRD analysis experiments were performed for each of the sintered bodies of Examples 1 to 3 and Comparative Examples 4 to 5 prepared in Experimental Example 2, and the results are shown in FIGS. 8A (Example 1) and 8B (Example). Example 2), FIG. 8C (Example 3), FIG. 8D (Comparative Example 4), and FIG. 8E (Comparative Example 5).

8A to 8E, Examples 1 to 3 and Comparative Examples 4 to 5 can confirm that apatite precipitation occurs first at 750 ° C., in particular, the more beta-walastonite is used as the bioactive glass powder containing much MgO is used. It can be seen that there is a tendency for the split to occur around 30 °, which is the main peak of, because the crystal phase of wollastonite substituted with Mg at the Ca site of beta wollastonite and pure beta wollastonite coexist. It is because of this.

And when comparing FIG. 8A (Example 1) and FIG. 8E (Comparative Example 5), there was no significant difference on the XRD data, but Comparative Example 5 had a problem in that the sintering characteristics are somewhat lower than that of Example 1.

In addition, comparing FIG. 8B (Example 2) and FIG. 8D (Comparative Example 4), although the comparative example 4 has a higher P ₂ O ₅ content than Example 2, the intensity of the beta wollastonite peak is higher Showed a tendency. Therefore, it is determined that Example 2 has a higher mechanical strength than Comparative Example 4.

In addition, in the case of FIG. 8C (Example 3), although the sintering characteristics are slightly lower than those of Examples 1 and 2, the sintering characteristics are relatively excellent even though the P ₂ O ₅ content is high.

(2) X-ray diffraction measurement results of the pulverized product of the sintered compact of Example 1 sintered at 1,000 ° C. are shown in Fig. 8F and Table 7 below.

Division (% by weight)	CaSiO 3	Apatite	Ca 2 Mg (Si 2 O 7 )	CaMgSi 2 O 6	Weight ratio
Example 1	17.1	50.5	17.1	15.3	1: 2.953: 1: 0.895

Experimental Example  4: measurement of crystallized microstructure of sintered body

The crystallized glass surface of the sintered compact with respect to the sintered compact sintered at 1,050 degreeC of Examples 1-3 was observed with the electron microscope, and the result is shown in FIG.

Looking at Figure 9, it can be seen that Examples 1 to 3 all have a very dense structure with little pores on the surface.

Experimental Example  5: of sintered body Bioactivity  And cytotoxicity assessment

The bioactivity and cytotoxicity of each of the sintered bodies sintered at 1,050 ° C. of Examples 1 to 3 were measured.

(1) The bioactivity was performed through a pseudo body fluid (SBF) deposition experiment, each of the sintered body was completely deposited in the pseudo body fluid for 24 hours, and then confirmed the formation of apatite carbonate layer through an electron microscope, the results It is shown in Figure 10a.

Looking at Figure 10a, it was confirmed that the sintered body of Examples 1 to 3 evenly formed a layer of apatite carbonate on the surface of the sintered body within 24 hours of the pseudo-body deposition experiment, it was confirmed that the Examples 1 to 3 have excellent bioactivity Could.

(2) In addition, the cytotoxicity evaluation was performed in-vitro experiments through SaOS-2 cell culture and the results are shown in Figure 10b.

The cytotoxicity test was performed as part of the biocompatibility test, and the extract test method of in vitro methods (ISO 10993-5) (: Biological Evaluation of Medical Devices, Part 5: Tests for Cytotoxicity) was used to test. The test solution used in the test was prepared by eluting the test substance with physiological saline and mixing the same amount with 2 × MEM (Modified Eagle's Medium) serum medium. The test solution was prepared on three rat fibroblasts with a uniform monolayer. Administered. At the same time, three solvent control groups, a negative control group, and a positive control group were also administered. All cells were incubated for 48 hours on (37 ± 1) ° C., (5 ± 1)% CO ₂ , after which the morphological changes of each cell were observed under a microscope.

And the sintered compact (HA) manufactured by the comparative example 7 was used as a control.

Looking at Figure 10b, when compared with the control, in Examples 1 to 3 all showed a low cytotoxicity, in particular, the sintered compact of Example 1 showed the lowest cytotoxicity.

Experimental Example  6: Experimental Measurement of Mechanical Properties of Sintered Body

In addition, the compressive strength, the bending strength, and the fracture toughness of the sintered bodies (which are 1050 ° C sintered bodies) of Examples 1 to 3 and Comparative Examples 1 to 7 were measured, and the results are shown in Table 8 below. The final sintered body was made of a 1 cm long cube and polished to homogenize the face to minimize the strength measurement error.

division	Compressive strength (Mpa)	Bending strength (Mpa)	Fracture Toughness (Mpa · m 1/2 )
Example 1	1321 ± 40	253 ± 13	3.0 ± 0.17
Example 2	1115 ± 45	241 ± 23	2.32 ± 0.05
Example 3	949 ± 77	170 ± 14	2.06 ± 0.06
Comparative Example 6	1103 ± 94	180 ± 10	1.54 ± 0.07
Comparative Example 7	832 ± 35	53 ± 1	1.51 ± 0.03

Looking at Table 8, it can be seen that Examples 1 to 3 all have excellent compressive strength, bending strength and fracture toughness.

And P ₂ O ₅ Content P ₂ O ₅ than Example 3 using a bioactive glass powder in the range of 18.5 ~ 19.8% by weight Content Examples 1 to 2 using bioactive glass powders in the range of 13.5 to 17 wt% showed relatively good mechanical properties.

In the case of Example 1, the compressive strength increased by 20% and 60% and the bending strength increased by 40% and 375% when compared with Comparative Examples 6 to 7. In addition, the fracture toughness was found to increase significantly by about two times for both. And Examples 2 and 3, it was confirmed that the fracture toughness value is more than 2 Mpa.m ^1/2 or more than Comparative Examples 6-7.

Experimental Example  7: Test of biocompatibility of sintered body

(1) Biocompatibility Visual Inspection

The biocompatibility visual inspection was performed about the 1050 degreeC sintered compact of Examples 1-2 and the sintered compact of comparative example 7.

The biocompatibility visual examination was performed by performing an autopsy to confirm the union and separation of the cortical bone, which is a hard outer portion, and the object artificially inserted into the region.

Visual inspection was performed on 11 subjects who underwent necropsy and the results are shown in FIGS. 11A (Example 1), 11B (Example 2), and FIG. 11C (Comparative Example 7).

In Comparative Example 7, two cases were found to be fused in short-term follow-up, but one case showed cortical bone and implant separation (see FIG. 11C).

On the contrary, in the case of Example 1 and Example 2, the two cases of long-term follow-up showed good union with the cortical bone, and both of the short-term follow-up showed a union with the cortical bone (see FIGS. 11A and 11B). ).

(2) radiological examination 1

Radiographic examinations were carried out for the 1050 ° C sintered bodies of Examples 1 to 2 and the sintered bodies of Comparative Example 7.

In the case of short-term drilling, autopsy was performed at 3 months postoperatively. For long-term follow-up, autopsy was performed at 8 months postoperatively, showing continuity and similar flexural strength and elasticity. If the union had no movement, it was determined as complete union.

As a result, in the case of Example 1, both cases of long-term follow-up were completely union with the cortical bone, and autopsy was performed in two cases of short-term follow-up. In addition, Example 2 also showed complete union with the cortical bone in both cases of long-term follow-up, and cortical bone and union in one of the two short-term patients, and partial union in one.

In contrast, in Comparative Example 7, there were 3 cases of complete fusion in 1 case and partial union in 2 cases.

(3) Radiological  Check 2

Radiographic examinations were carried out for the 1050 ° C sintered bodies of Examples 1 to 2 and the sintered bodies of Comparative Example 7.

In the case of short-term drilling, radiographic examinations are performed at intervals of two weeks immediately after surgery and up to 12 weeks thereafter, and long-term follow-up examinations are performed on the tibia of the rabbit every 12 months after 12 weeks of union. The degree was observed.

Radiographic examinations were taken every two weeks, Before and after 3 months after the operation, the radiographs are shown in FIGS. 12A (Example 1), 12B (Example 2), and FIG. 12C (Comparative Example 7), respectively.

As a result of the measurement, fractures were observed in the distal portion of the transplantation in one case of Example 1 and one case of Comparative Example 7. Then, the transplantation confirmed that the fusion progressed.

(4) histological and tensile tests

Histological and tensile tests of the sintered compacts of Examples 1 to 2 and the sintered compacts of Comparative Example 7 were carried out.

Histological examination refers to the examination of the human or animal tissues by ablation and observation with an optical microscope. In this study, non-calcified slides were made and subjected to H & E (Hematoxylin & eosin) staining, and then histological examination of the implants with optical microscope. . In the tensile test, the implant was inserted below the proximal tibia surface of the rabbit and the external fixation device was shortened and fixed so that the compressive force acted on the insertion site. Three months after the operation, the bolt screw was inserted to pass through the center of the upper and lower tibia, which was in contact with the implant, and the pre-fabricated fixing mechanism was installed at the same interval. At this time, the tensile force is applied to the front and rear evenly so that the rotational stress is not applied. And the result was shown to FIG. 13A (Example 1), FIG. 13B (Example 2), and FIG. 13C (Comparative Example 7).

Looking at Figure 13, it shows the observation of the binding state of the graft and bone to the non-calcified tissue. In Examples 1 and 2 and Comparative Example 7 it can be confirmed that the union with the bone was well. However, looking at Figure 13b, it can be confirmed that the property is broken, not because of the strength of the specimen, it is determined that the excessive load due to fracture.

Production Example  1: Preparation of disk-shaped artificial bone tissue

A block-shaped molded article (a medicinal material for replacing amorphous biohard tissue defects) prepared by heat treatment at 700 ° C. prepared in Example 1 was analyzed by analyzing the disk shape modeling results as shown in FIG. The molded body was processed after redesign by applying a shrinkage rate of 18% to each side.

Next, the processed molded body was calcined at 1,050 ° C., and then artificial bone tissue was prepared, which is a final sintered body in the form of a disk obtained by slow cooling at 2 ° C./min (see FIG. 15).

The artificial bone tissue produced showed a deviation within 5% of the predictive design (see Table 9 below).

division	A (mm)	B (mm)	C (mm)
design	24.5	18.7	7.4
Found	24.86 ± 0.13	18.53 ± 0.15	7.57 ± 0.49
error	0.16%	0.9%	2.3%

Production Example  2: preparation of artificial bone tissue in the form of spine

A block-shaped molded article prepared by heat treatment at 700 ° C. prepared in Example 1 (a substitute for non-crystalline biohard tissue defects) was analyzed by analyzing modeling results of the spine and shapes as shown in FIG. The molded body was processed (see FIG. 17A).

Next, an artificial bone tissue, which is a final sintered sintered body obtained by sintering the molded body processed into the spine form at 1,050 ° C. and then slowly cooled to 2 ° C./min, was prepared (see FIG. 17B).

In addition, when the artificial bone tissue was matched with the prototype produced by 3D printing in the same spine shape, it was confirmed that the manufacturing process was excellent in the implementation effect on the shape (FIG. 18).

Production Example  3: spine Spacer  Manufacture and Characterization thereof

After treating the medicinal material for replacing the amorphous living hard tissue defect part of Example 1 in the form of a spine spacer, it was calcined at 1,050 ° C to prepare a spinal spacer as a sintered body.

The clinical results of the human spine using the manufactured spinal spacer showed a similar level of union with the surrounding bone compared to the autogenous bone implanted into the titanium cage, which is a common surgical method (control). Thirty-five (89.7%) of 39 subjects with the spacer implanted in the lumbar spine had excellent clinical results at 12 months. In particular, as a result of calculating the bonded area between the vertebral body and the spacer, as shown in Table 9, the bonding area for the spacer of the crystallized glass ceramic material according to the present invention was statistically significantly higher than the autogenous bone filled in the titanium cage ( p <0.001). The area of spacer or autogenous bone associated with the calculated vertebral endplates is compared in Table 10.

division	Upper vertebral endplate	Lower vertebral endplate
Invention (Example 1)	86.0 ± 48.0 mm 2	81.4 ± 48.6 mm 2
Control	36.4 ± 16.1 mm 2	39.3 ± 14.7 mm 2

The present invention described above is not limited to the above-described embodiments and the accompanying drawings, and various substitutions, modifications, and changes are possible within the scope without departing from the technical spirit of the present invention. It will be apparent to those who have knowledge.

Claims (24)

1. A bioactive glass powder comprising a ground material obtained by heat treatment of a mixture comprising MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ .
2. According to claim 1, wherein the mixture is MgO 4.5 to 6.5 wt%, CaO 41 to 43.0 wt%, SiO ₂ 34 to 36.2 wt%, P ₂ O ₅ 13.5 to 17 wt%, CaF ₂ 0.90 to 2.5 wt% and B ₂ O ₃ Bioactive glass powder comprising 0.2 to 1.5% by weight.
3. According to claim 1, wherein the mixture is MgO 4.5 to 6.5 wt%, CaO 41 to 43.0 wt%, SiO ₂ 30.5 to 32.5 wt%, P ₂ O ₅ 18.5 to 19.8 wt%, CaF ₂ 0.5 to 1.5 wt% and B ₂ O ₃ Bioactive glass powder comprising 0.2 to 1.5% by weight.
4. The bioactive glass powder according to claim 1, wherein the mixture comprises Na ₂ O.
5. A medicinal material for replacing an amorphous living hard tissue defect, comprising the bioactive glass powder of any one of claims 1 to 4.
6. The medicinal material for replacing a non-crystalline biohard tissue defect according to claim 5, wherein the compressed molded product of the bioactive glass powder is subjected to a heat treatment at a temperature below the glass transition temperature of the bioactive glass powder in the molding.
7. The non-crystalline living body hard tissue according to claim 6, wherein the amorphous molded body is a molded body obtained by heat-treating the compression molded body at 680 ° C to 720 ° C. Replacement material for defective parts.
8. The method of claim 7, wherein the amorphous molded article has a crystallinity of 1% or less, medicinal material for replacing the amorphous living hard tissue defects.
9. The method of claim 8, wherein the amorphous molded article has a relative density of 50 to 70% relative to the glass theoretical density (3g / cm ³ ), the medicinal material for replacing the amorphous living hard tissue defects.
10. 1 step of preparing a bioactive glass powder;

    Step 2 to produce a molded body by pressing the bioactive glass powder; And

    And heat-treating the molded body at a temperature below the glass transition temperature of the bioactive glass powder in the molded article to produce an amorphous molded body. 3.
11. The method of claim 10, wherein the step 1 bioactive glass powder

    1-1 step of melting the mixture containing MgO, CaO, SiO ₂ , P ₂ O ₅ , CaF ₂ and B ₂ O ₃ at 1350 ° C. to 1600 ° C. to obtain a melt;

    Quenching the melt to prepare glass;

    Method of manufacturing a medicinal material for replacing the amorphous living hard tissue defects, characterized in that for performing a process comprising a; 1-3 to powder the glass.
12. The method of claim 10, wherein the heat treatment in three steps is performed at 680 ° C. to 720 ° C. 12.
13. A step 1 of manufacturing a workpiece by processing the medicinal material for replacing the amorphous living hard tissue defect of claim 5; And

    And firing the workpiece to prepare a fired product. 2.
14. The method of claim 13, further comprising three steps of slowly cooling the calcined product.
15. The method of claim 13, wherein the processing of the first step comprises: photographing the processing target bone tissue to generate three-dimensional image information of the processing target bone tissue; Identifying the processing target bone tissue based on the three-dimensional image information of the processing target bone tissue, and generating three-dimensional image information of at least one processing target bone tissue model corresponding to the processing target bone tissue; Verifying suitability of the at least one bone tissue model to be processed; In the verifying step, determining the three-dimensional image information of the processing target bone tissue model when there is no correction of the three-dimensional image information of the at least one processing target tissue model; In the verifying step, when there is correction information of the three-dimensional information of the at least one processing target bone tissue model, the three-dimensional image of the processing target bone tissue model by reflecting the correction information in the three-dimensional image information of the processing target bone tissue model Confirming the information; And processing the workpiece in the form of artificial bone tissue from the 3D image information of the determined bone tissue model of the processing target.
16. The method of claim 13, wherein the firing is performed at 850 ° C to 1,200 ° C.
17. A plastic material of the medicinal material for replacing the amorphous living hard tissue defect of claim 5,

    The fired product is artificial bone tissue, characterized in that containing CaSiO ₃ .
18. The method of claim 17, wherein the calcined product is Ca ₁₀ (PO ₄ ) ₆ A, wherein A is an oxygen atom. And Apatite containing at least one selected from Ca ₁₀ (PO ₄ ) ₆ B ₂ , wherein B is a hydroxyl group, a fluorine atom, or a chlorine atom; Ca ₂ Mg (Si ₂ O ₇ ); And CaMgSi ₂ O ₆ Artificial bone tissue characterized in that it further comprises at least one selected from.
19. 19. The method according to claim 18, wherein the artificial bone tissue comprises CaSiO ₃ , the apatite, Ca ₂ Mg (Si ₂ O ₇ ) and CaMgSi ₂ O ₆ in 1: 1: 0.7 to 3.0: 0.5 to 1.2: 0.7 to 1.3 weight ratio Artificial bone tissue.
20. 18. The artificial bone tissue of claim 17 wherein the artificial bone tissue is in a crystalline phase.
21. 18. The artificial bone tissue according to claim 17, wherein the compressive strength is 900 to 1,600 Mpa and the torsional strength is 0.6 Nm to 2.0 Nm.
22. 18. The artificial bone tissue according to claim 17, wherein the volume shrinkage ratio is 5% or less based on the length in the uniaxial direction of the shape of the hard tissue defect of the living body.
23. 18. The artificial bone tissue according to claim 17, wherein the relative density value of the fired material is 95% or more of the glass theoretical density.
24. 18. The artificial bone tissue of claim 17 wherein the artificial bone tissue comprises artificial bone, artificial joint, oral and maxillofacial bone, skull, or dental artificial tooth root.

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