KR102123540B1 - Method for preparing bone grafting substitutes comprising ceramic granules - Google Patents

Abstract

The present invention relates to a method for manufacturing a bone graft material in the form of a combination of ceramic particles having a plurality of holes (holes) penetrating the entire particle and a bone graft material produced thereby, the method for manufacturing a bone graft material according to the present invention is molded By modifying the shape of the product as desired, various products can be developed, and the shape of the bone graft material can be manufactured to fit the shape of the treatment site, thereby providing convenience for the procedure.
In addition, it is effective to control mechanical properties such as porosity and mechanical compressive strength by various types of particles entering the mold.
Furthermore, the bone graft material produced by the production method according to the present invention not only facilitates cell adhesion, but also has excellent effects in strength and biocompatibility.

Description

Method for preparing bone grafting substitutes comprising ceramic granules

The present invention relates to a method for manufacturing a bone graft material in the form of a combination of ceramic particles having a plurality of holes (holes) penetrating the entire particle and a bone graft material produced thereby.

Hard tissue transplantation from the patient (autograft) or from the donor (allograft or xenograft) is required at the site of the defect to support mechanical stress and to increase natural bone regeneration and treatment.

Recently, bone graft material has been receiving medical attention as a substitute for damaged bone or as a filler for hard tissue joints.

The best method for bone graft is autograft, that is, transplantation from other parts of the body, but there are limitations depending on the recipient's condition and the likelihood of harvesting. Therefore, bone grafts made from animal or carcass bones have been applied to the clinic. As an example, Korean Patent Publication No. 2010-0080028 discloses a method for producing a sponge-like bone graft material by collecting degenerative, deliming, washing, and sterilizing processes in a short time by collecting allogeneic or heterogeneous bone tissue. However, bone grafts using allogeneic or heterogeneous bone tissue can be exposed to potential infections such as mad cow disease or AIDS.

To improve these problems, calcium-phosphate-based ceramic bone grafts such as hydroxyapatite (HAp), tricalcium phosphate (α/β-TCP) and biphasic calcium phosphate (BCP), which are similar to those of natural bones, are being developed, especially BCP. Ceramics are used in dentistry, orthopedics, etc. because of their balance of mechanical strength and biodegradability.

On the other hand, hard tissue replacement materials have different requirements depending on the clinical application.

If the defect site is large, a block-type bone graft material is required, but since a long time is required in the manufacturing process, there is a limit in manufacturing a bone graft material having the shape most suitable for the defect site. As an example, in Korean Patent Publication No. 2010-0061649, a step of preparing a porous block-type synthetic ceramic support, mixing an aqueous solution of a multi-branched PEG-thiol and an aqueous solution of a multi-branched PEG-acrylate having a total sum of branches greater than or equal to 5 Disclosed is a composite bone repair material prepared by a step of immersing the porous block-type synthetic ceramic support in the mixture. However, such a block-type bone graft material has a disadvantage of exhibiting a slow biodegradable property because it has a thick skeletal structure.

In the case of the implant-type bone graft material, the above-described disadvantages of the block-type bone graft material may be compensated, but the porosity, which is an important factor influencing remineralization and bone formation, cannot be controlled, and the strength is low.

Granular bone graft material has the potential to compensate for the above disadvantages and has excellent strength and easy applicability, and thus can be used as an excellent bone graft material. However, since these granular bone grafts are in a state in which the respective granules are not combined with each other and are separated, in order to fill a defect site during surgery, a tool such as a syringe or a spoon is used after transferring in grain units or mixing an independent viscous material in a certain space. There was a discomfort that must be used.

Korean Patent Publication No. 2010-0080028 (published on July 8, 2010) Korean Patent Publication No. 2010-0061649 (published on June 8, 2010)

The present invention has been made to solve the above problems, and has an object to provide a method of manufacturing a bone graft material that is easy to manufacture in a desired shape using a mold.

In addition, the present invention has an object to provide a bone graft material having excellent strength and excellent biocompatibility.

According to a preferred embodiment of the present invention, a method of manufacturing a bone graft material comprises: first extruding a composite composed of a carbon filament core and a ceramic shell to obtain a plurality of primary filaments; Placing the plurality of primary filaments therein, positioning the ceramic shell outside, and then extruding them to obtain secondary filaments; Cutting the secondary filaments to obtain ceramic particles; After injecting the ceramic particles into a mold, heating to obtain a ceramic molded body; And sintering the ceramic molded body.

The extrusion may be characterized in that proceeds at a speed of 2 ~ 5 mm / mim.

The primary filament may be characterized in that it has a diameter size of 0.1 to 10 mm and a length of 1 to 50 mm.

The secondary filament may be characterized in that it has a diameter size of 0.1 to 50 mm and a length of 0.5 to 50 mm.

The ceramic particles may be characterized as having a length of 0.1 ~ 10 mm.

The heating may be performed at a temperature of 30 to 150° C. for 10 minutes to 5 hours.

The step of sintering the ceramic molded body may be characterized in that it is first sintered at a temperature of 500 to 1,000°C, and then secondary sintered at a temperature of 1,000 to 1,300°C.

The bone graft material may be characterized by including ceramic particles having a plurality of holes (holes) penetrating the entire particle.

The hole of the ceramic particles may be characterized by having a diameter size of 50 ~ 1,000㎛.

The method for manufacturing a bone graft material according to the present invention enables various product developments by deforming the shape of the mold as desired, and thus the shape of the bone graft material can be manufactured to match the shape of the treatment site, thereby providing convenience for the procedure. It has an effect.

In addition, it is effective to control mechanical properties such as porosity and mechanical compressive strength by various types of particles entering the mold.

Furthermore, the bone graft material produced by the production method according to the present invention not only facilitates cell adhesion, but also has excellent effects in strength and biocompatibility.

1 is a schematic diagram of the extrusion process of the primary filament and the secondary filament in the process of manufacturing ceramic particles according to the present invention.
2 is a photograph showing ceramic particles manufactured according to the present invention.
3 is a photograph showing a ceramic molding agent in the form of Ÿ‡ paper manufactured according to the present invention.
4 is a photograph showing a bone graft material prepared according to the present invention.
5 is an SEM image of the surface of the bone graft material prepared according to the present invention.
6 is a photograph showing various types of bone graft material prepared by changing the shape of the mold.
7 is a photograph showing a Ÿ‡ topography bone graft material prepared by varying the size of particles.
8 is a photograph showing a block-type bone graft material prepared by varying the size of particles.

Hereinafter, the present invention will be described in detail. Prior to this, the terms or words used in the present specification and claims should not be construed as being limited to ordinary or lexical meanings, and the inventor appropriately explains the concept of terms in order to explain his or her invention in the best way. Based on the principle that it can be defined, it should be interpreted as meanings and concepts consistent with the technical spirit of the present invention. Therefore, the configuration described in the embodiments described herein is only one of the most preferred embodiments of the present invention and does not represent all of the technical spirit of the present invention, and various equivalents that can replace them at the time of this application It should be understood that there may be variations.

In the present invention, the term'bone graft material' is also referred to as a'bone filler', a'bone substitute', and a'bone supporter', and is defined as transplantation when a part of the bone tissue in the living body is missing or requires reinforcement.

The method for manufacturing a bone graft material of the present invention comprises the steps of: first extruding a composite composed of a carbon filament core and a ceramic shell to obtain a plurality of primary filaments;

Placing the plurality of primary filaments therein, positioning the ceramic shell outside, and then extruding them to obtain secondary filaments;

Cutting the secondary filaments to obtain ceramic particles;

After injecting the ceramic particles into a mold, heating to obtain a ceramic molded body; And

And sintering the ceramic molded body.

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

First, a composite composed of a carbon filament core and a ceramic shell is first extruded to obtain a plurality of primary filaments. More specifically, a ceramic shell, which is a biomaterial, is placed around the carbon filament core for forming a hole, and is first extruded to form a primary filament having one carbon core.

The ceramic shell may be composed of a mixture of ceramic powder and binder, and the mixture may be preferably mixed in a shear mixer.

The type of the ceramic powder as the biomaterial is not particularly limited, but preferably, tricalcium phosphate (TCP) or hydroxyapatite (HAp) is used, or a mixture of them is bi-phasic calcium phosphate. (biphasic calciumphosphate, BCP) can be used.

In addition, the type of the binder is not particularly limited, but preferably, ethylene vinyl acetate (EVA), polyethylene (polyethylene), wax (wax), polypropylene (polypropylene), paraffin (praffin), etc. may be used, Most preferably, EVA can be used.

In addition, the mixture is stearic acid (CH ₃ (CH ₂ ) ₁₆ COOH), polyethylene waxes, oxidized polyethylene waxes, esters, amides (e.g. oleamide, erucamide) , Fatty acids (for example, lauric acid, myristic acid, palmitic acid) and the like.

The carbon filament may be prepared by mixing the carbon powder with the binder or lubricant and then extruding.

The binder or lubricant is used to maintain the viscosities of the carbon filament and ceramic shell, and may contribute to creating a microstructure during extrusion.

The composite composed of the carbon filament core and the ceramic shell is first extruded to obtain a plurality of primary filaments.

In the step of obtaining the plurality of primary filaments, it is possible to control the porosity of the final bone graft material by adjusting the size of the outer diameter of the primary filament during primary extrusion.

Here, the primary filament may be characterized as having a diameter size of 0.1 ~ 10 mm and a length of 1 ~ 50 mm.

More specifically, the primary filament may have a diameter size of 0.1 to 10 mm and a length of 1 to 50 mm, preferably a diameter size of 0.1 to 5 mm and a length of 1 to 30 mm. .

Next, a plurality of primary filaments prepared above are placed inside, and a ceramic shell is placed outside, followed by secondary extrusion to obtain secondary filaments.

At this time, by changing the quantity of the plurality of primary filaments placed therein, the number of holes of the ceramic particles produced by cutting the secondary filaments can be adjusted later, and the porosity and mechanical strength of the final bone graft material can be controlled.

In addition, by changing the diameters of the plurality of primary filaments placed therein, the diameters of the holes of the ceramic particles produced by cutting the secondary filaments can be adjusted later, and the porosity and mechanical strength of the final bone graft material can be controlled.

Here, the secondary filament may be characterized in that it has a diameter size of 0.1 ~ 50 mm and a length of 0.5 ~ 50 mm.

More specifically, the secondary filament may have a diameter size of 0.1 to 50 mm and a length of 0.5 to 50 mm, preferably a diameter size of 0.5 to 50 mm and a length of 1 to 30 mm.

The primary extrusion and secondary extrusion may be performed at a speed of 2 to 5 mm/mim.

If the extrusion proceeds at a speed outside the above-described range, the strength of the resulting primary filament or secondary filament may be lowered, or high pressure may be required during extrusion.

Subsequently, the secondary filament is cut to obtain ceramic particles.

At this time, the ceramic particles may be preferably cut to have a length of 0.1 to 10 mm, preferably cut to have a length of 0.2 to 7 mm, and more preferably 0.5 to 5 mm. It can be made by cutting to length.

If the length or size of the ceramic particles is too short or small, it is difficult to form a hole through the particles, and if the length or size of the ceramic particles is too long or large, space between the particles increases, which may cause a decrease in strength.

The length or size of the ceramic particles can be adjusted within an appropriate range according to the size of the final bone graft material, and can be adjusted by changing the quantity and diameter of a plurality of primary filaments placed therein during extrusion of the secondary filaments.

The ceramic particles may have a cylindrical shape as an example, but are not limited thereto.

The ceramic particles may have different mechanical properties, such as porosity and compressive strength, even in the same type of bone graft material according to their length or size, thereby controlling the bone graft material with various mechanical properties.

Next, the ceramic particles are injected into a mold, and then heated to obtain a ceramic molded body.

The length or size of the ceramic particles can be adjusted within an appropriate range according to the size and shape of the mold, and can be adjusted by changing the quantity and diameter of a plurality of primary filaments placed therein during the secondary filament extrusion.

Here, after the ceramic particles are injected into the mold, a ceramic molded body can be obtained by heating under pressure conditions.

The mold may have various forms such as a wedge type, a mat type, a chip type, and a block type, through which various types of product development may be possible. .

In order to inject the ceramic particles into the mold, the heating may be performed at a temperature of 30 to 150° C. for 10 minutes to 5 hours.

The heating may be performed at a temperature of 30 to 150°C, for 10 minutes to 5 hours, preferably at a temperature of 60 to 120°C, for 20 minutes to 3 hours, more preferably 70 to 100°C At a temperature of 30 minutes to 2 hours.

If, when heated to a temperature of less than 30 ℃, the bonding between the ceramic particles to form a ceramic shaped body may not proceed sufficiently or the heating time may be long, and when heated above the temperature of 150 ℃, the molded body is deformed or unnecessary high temperature process This may be required.

In addition, when heated for less than 10 minutes, a ceramic molded body may not be formed, and when heated for more than 5 hours, the ceramic molded body may be deformed or the process time may be unnecessarily long.

Subsequently, a bone graft material may be obtained by sintering the ceramic molded body.

Here, the step of sintering the ceramic molded body may be performed by primary sintering at a temperature of 500 to 1,000°C, followed by secondary sintering at a temperature of 1,000 to 1,300°C.

More specifically, the primary sintering can be carried out by slowly increasing the temperature in a temperature range of 500 to 1,000°C, preferably 650 to 900°C for 100 to 120 hours in an N ₂ atmosphere, which is an inert atmosphere, to remove the binder, 2 Secondary sintering can be carried out by gradually raising the temperature in the atmosphere to a temperature range of 1,000 to 1,300°C to remove carbon and increase bonding between ceramic particles.

Here, the binder and the carbon component can be removed while preventing deformation of the particles by maintaining the temperature range and the time required to reach the temperature range. In addition, fine pores in the particle may be formed through the removal of the binder, and a hole through the particle may be formed through the removal of the carbon component.

The method for manufacturing the bone graft material may proceed to a washing step after the sintering step.

The washing step may be performed by heating deionized water to 40 to 60° C. in an ultrasonic cleaner and then washing the bone graft material through a sintering process twice for 5 minutes.

Thereafter, the washed bone graft material may be completely dried in an oven at 60 to 100°C for 1 to 3 days.

The bone graft material may be characterized by including ceramic particles having a plurality of holes (holes) penetrating the entire particle.

The hole of the ceramic particles may have a diameter size of 50 ~ 1,000㎛, preferably may have a diameter of 50 ~ 700㎛, more preferably may have a diameter of 100 ~ 300㎛.

Here, when the hole of the ceramic particles is formed below the diameter described above, it is difficult for the bone tissue cells to penetrate sufficiently into the pores, and thus the proliferation rate of the bone cells is lowered, and when the hole is formed above the diameter described above, the bone strength is decreased by the internal space. Can be a problem.

The size of the hole of the ceramic particles can be controlled by the size of the carbon filament core.

The ceramic particles may have a cylindrical shape as an example, and the plurality of holes may be vertically formed in a channel shape to penetrate the upper and lower surfaces of the cylinder, but if a plurality of holes penetrating the entire particle can be formed The shape of the ceramic particles is not limited to this.

In addition, the ceramic particles may include 3 to 20 holes, and may be adjusted to a suitable number according to the situation.

The above description is merely illustrative of the technical idea of the present invention, and those of ordinary skill in the art to which the present invention pertains will be capable of various modifications and variations without departing from the essential characteristics of the present invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to explain, and the scope of the technical spirit of the present invention is not limited by these embodiments. The scope of protection of the present invention should be interpreted by the following claims, and all technical spirits within the equivalent range should be interpreted as being included in the scope of the present invention.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

<Example 1> Preparation of bone graft material

First, β-TCP (β-Tricalcium phosphate) powder was prepared, and carbon powder (15 μm, Aldrich, USA) was prepared for the production of filaments.

In addition, EVA (ethylene vinyl acetate) (ELVAX 210 and 250, Dupont, USA) was used as a binder, and stearic acid (Daejung Chemicals & Metals Co. Korea) was used as a lubricant.

Ceramic shell (β-TCP 48 vol%/EVA 42 vol%/stearic acid 10 vol%) and carbon filament core (carbon 48 vol%/EVA 42 vol%) using a shear mixer process (Shina Platec, Korea) / Stearic acid 10 vol%) was prepared.

Subsequently, the ceramic shell was placed in a form surrounding the carbon filament core, and the extrusion die was extruded at a speed of 3 mm/mim to extrude the primary filament, and the 7 primary filaments were wrapped with 2 ceramic shells, and then 3 mm. Secondary extrusion was performed at a rate of /mim to obtain secondary filaments (see FIG. 1).

Next, the secondary filament was cut to a length of 0.7 mm to obtain ceramic particles (see FIG. 2).

Subsequently, the ceramic particles were filled into a mold in the form of Ÿ‡ paper and then heated at 80° C. for 1 hour under pressurized conditions to obtain a ceramic molded body (see FIG. 3 ).

The obtained ceramic molded body was degreased by performing a primary heat treatment for 5 days by slowly raising the temperature to 800° C. in an N ₂ atmosphere to remove the binder.

Next, heat treatment was performed at 1,100° C. under an air atmosphere to completely remove the carbon component to form a hole having a diameter of about 300 μm on average, and strength was increased by strengthening the bonding between the ceramic particles (see FIG. 4 ).

Thereafter, deionized water was added to an ultrasonic cleaner, heated to 50° C., and then the obtained bone graft material was added, washed twice for 5 minutes, and completely dried in an oven at 80° C. for 2 days.

<Experimental Example 1> Measurement of surface shape of bone graft material

The surface shape of the bone graft material prepared in Example 1 was measured by SEM and is shown in FIG. 5.

As shown in FIG. 5, it was confirmed that the bone graft material prepared in Example 1 was formed with a plurality of through holes.

<Experimental Example 2> Porosity measurement of bone graft material

The porosity of the bone graft material prepared in Example 1 was measured.

As a result, it was confirmed that the porosity of the bone graft material prepared in Example 1 showed a result value of about 60%.

Claims (9)

First extruding a composite composed of a carbon filament core and a ceramic shell to obtain a plurality of primary filaments;
Placing the plurality of primary filaments therein, positioning the ceramic shell outside, and then extruding them to obtain secondary filaments;
Cutting the secondary filament to obtain ceramic particles having a length of 0.5 to 5 mm and having a plurality of holes having a diameter of 50 to 1,000 μm penetrating the entire particle;
After injecting the ceramic particles into a mold, heating at a temperature of 30 to 150° C. for 10 minutes to 5 hours to obtain a ceramic molded body; And
The first step of sintering the ceramic molded body at a temperature of 650 ~ 900 ℃ for 100 ~ 120 hours, and secondly sintering at a temperature of 1,000 ~ 1,300 ℃ to obtain a bone graft material,
The bone graft material is a method for manufacturing a bone graft material, characterized in that the hole passing through the entire particle and the pores between the particles are randomly formed in three dimensions.
According to claim 1,
The extrusion method of the bone graft material, characterized in that proceeds at a speed of 2 ~ 5 mm / mim.
According to claim 1,
The primary filament is a method of manufacturing a bone graft material characterized in that it has a diameter size of 0.1 to 10 mm and a length of 1 to 50 mm.
According to claim 1,
The secondary filament is a method of manufacturing a bone graft material characterized in that it has a diameter size of 0.1 to 50 mm and a length of 0.5 to 50 mm.
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