KR101762580B1

KR101762580B1 - A method for preparing porous bone graft materials

Info

Publication number: KR101762580B1
Application number: KR1020150137169A
Authority: KR
Inventors: 이재준
Original assignee: (주)에스겔
Priority date: 2015-09-26
Filing date: 2015-09-26
Publication date: 2017-07-31
Also published as: KR20170038134A

Abstract

The present invention relates to a method for producing a porous bone graft material, particularly hydroxy aepi tight as the main component of the bone graft material (HA: Hydroxyapatite), beta-tri calcium phosphate (beta-TCP: Tricalcium β- Phosphate ) and silk fibers.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a porous bone graft material,

The present invention relates to a method for producing a porous bone graft material, particularly hydroxy aepi tight as the main component of the bone graft material (HA: Hydroxyapatite), beta-tri calcium phosphate (beta-TCP: Tricalcium β- Phosphate , and silk fibers. &Lt; Desc / Clms Page number 2 >

The bone tissue is the only hard tissue in the body, and when the bone tissue is damaged due to trauma, tumor, deformity or physiological phenomenon, the bone is filled in that area to create new bone. As the most common method for recovering the bone defect, There is a method of autologous bone graft for collecting and grafting a part of one's own bone at another site, a method of allograft transplantation by chemically treating other bones, and a method of heterologous bone graft for chemically treating bone of an animal. The autogenous bone grafting method, which is a good grafting method, has a disadvantage in that secondary operation is necessary, it is difficult to obtain the necessary amount, and it is difficult to perform in a general clinic. Allograft transplantation method can cause immune reaction, There is a risk of introducing viruses such as AIDS and hepatitis into patients, Also it has the disadvantage that it is a problem with using the event of problems such as the problem of an immune response with mad cow disease. This can easily obtain a sufficient amount of bone, there is no infectious potential for disease, bone in biocompatibility with enough performance to replace existing implants can be excellent and is well absorbed when transplanted substituted goal play transplants (bone - grafting materials are required.

As a bone graft material developed according to this demand, it can be classified into metal, ceramic material and polymer depending on the material. Materials such as metal and ceramics are mainly used as hard tissue substitute materials such as teeth and bones. Recently, It is also used to combine ceramics with polymers or with metals and ceramics. In particular, ceramic materials have the advantage of being chemically bonded to bones in that apatite, which is an inorganic component of bones and teeth, is a ceramic.

Among the ceramic materials having such characteristics, in particular, bioactive ceramics include bioactive glasses mainly composed of calcium oxide (CaO) and silicon oxide (SiO ₂ ) glass , and calcium phosphate ceramics composed of calcium and phosphorus, which are the main components of bone.

Various calcium phosphate-based ceramic compounds have been developed as artificial bone grafts. As a typical example, hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ , hydroxyapatite ( HA ) Korean Patent Laid-Open Publication No. 2011-0097559 discloses a method for producing a phosphate compound selected from the group consisting of hydroxyapatite, oxyapatite, monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, calcium phosphate, calcium metaphosphate, Calcium silicate ceramics selected from the group consisting of calcium-based ceramics, tricalcium silicate, calcium orthosilicate, calcium disilicate, tricalcium disilicate, wollastonite, and mixtures thereof, sodium oxide, calcium oxide, Zirconia; and a mixture thereof. &Lt; RTI ID = 0.0 > And a CNT coating layer comprising a modified CNT represented by Chemical Formula 1 formed on the surface of the substrate. &Quot; The present invention relates to a ceramic / CNT composite comprising a substrate made of a bioactive ceramic selected from the group consisting of water, The HA with excellent biostability and bone conduction performance naturally fuses with the surrounding tissues after bone defect graft and restores the bone defect by biochemically binding to the remaining bone. However, as periodic follow - up is required due to the persistent nature of HA in the body, the need for biodegradable ceramic bone graft materials to induce new bone formation after biodegradation and absorption has emerged. Accordingly, in response to this demand, there is a tendency that new bone is biodegraded in the human body and absorbed into the surrounding tissues as a result of generation of new bone. As the calcium phosphate-based compound, calcium tertiary phosphate showing chemical properties similar to HA, especially beta-trisodium phosphate (β

_{-Ca 3 (PO 4) 2,} β- tricalcium phosphate ; β- TCP ) has been proposed and is widely used as an alternative to hard tissue substitutes in orthopedics and dentistry. This β-TCP has been applied to various products because it has the advantage of being decomposed and absorbed within several years after restoration of bone defect.

On the other hand, the ceramic bone graft materials having the above-mentioned characteristics can not be molded or processed in accordance with various types of bone defects due to the characteristics of ceramics, ( Granules ). In addition, magnetic graft-type bone graft materials have been developed due to lack of shape processing or formability. The initial autogenous bone graft material was a product mainly composed of HA, which is the same as the minerals of bone after curing. To date, various self-hardening bone graft materials based on HA have been commercialized. Self-hardening bone graft materials, like ceramic bone graft materials, were required to have biodegradable composition, and therefore, beta-trisodium phosphate and calcium dihydrogenphosphate (CaHPO ₄ 2H ₂ O, Dicalcium phosphate dihydrate; DCPD ) have been developed.

In addition, the most important component of the bone graft material is porosity, and the graft material including the pores having an average diameter of 150 to 850 μm is most preferable because it contributes to the growth of the new bone and the formation of surrounding tissues and blood vessels. Therefore, most of the ceramic bone graft materials are commercialized without regard to the components, and magnetic curing type bone graft materials are being developed in a form of high porosity. Ceramic bone graft materials manufactured by sintering can form macropores having a diameter of 50um or more by using a sponge manufacturing method or a foaming method. However, since a self-hardening bone graft material has a final structure determined by a hydration reaction, an artificial macropore can not be formed inside the product, and thus it is being developed as a product containing micropores of nanometers to several microunits. This is a disadvantage in that it can not provide macropores, which is an effective space for the tissue growth into the bone graft material and the delivery of the new bone, and thus, a structural improvement is needed to utilize it as a goal frame structure.

The present invention provides a biodegradable bone graft material that can be injected into a living body without side effects and is decomposed and absorbed in a living body after a lapse of a predetermined time. The present invention provides a biodegradable bone graft material capable of efficiently pouring the effective space for tissue growth and delivery of new bone To provide a bone graft that can be provided.

In order to achieve the above object, the present invention provides a method of manufacturing a honeycomb structure, comprising the steps of: mixing zirconia balls into ethanol by a half volume of ethanol, mixing HA and beta-TCP at the same weight ratio, mixing the mixture in a ball mill, A ball milling process at a speed of 24 to 36 hours, a step of holding the mixed solution having undergone the ball milling process at a predetermined mesh size, a step of drying the mixed solution at 60 ± 10 ° C. for 3 to 5 hours Drying the mixture at room temperature for 12 to 15 hours to completely remove ethanol, calcining the dried mixture in an alumina vessel in an electric furnace under predetermined conditions, preparing the BCP powder by calcination, After PVB was added, PVB was completely dissolved while stirring. Then TEP was added at the same weight ratio as PVB, and silk fiber was applied to PVB 5% by weight, the prepared BCP powder is mixed at a weight ratio of 5 times with respect to PVB and stirred for about one week to prepare a BCP slurry, and the prepared BCP slurry is mixed with a soft material such as wood and carbon black Coating the inner and outer surfaces of a cube block having a plurality of through holes (150 to 850 mu m in size) with a BCP slurry and then sintering in an electric furnace at 1250 DEG C to prepare a bone graft material. Mu m in size) of the bone graft material.

By providing the stem cell storage material according to the present invention, treatment according to bone damage not only reduces the risk of immunity rejection and infection of the patient but also improves the homeostasis in the defective tissue by culturing differentiated stem cells obtained from the human body I can keep it.

1 is a perspective view showing a bone graft material of a cubic structure according to the present invention.

Hereinafter, the present invention will be described in detail with reference to examples.

As a method for manufacturing a bone graft material according to the present invention, BCP (Bi-calcium phosphate) powder is prepared.

BCP prepared by using the powder to prepare a slurry BCP (slurry), and then made of a soft material of wood or carbon black jidoe to coat the slurry on the BCP blocks are formed a plurality of through holes (150 ~ 850 ㎛ size).

The block having the plurality of through holes coated with the BCP slurry was sintered in an electric furnace at 1250 캜 to produce a final porous bone graft material.

Example

One. BCP ( Bi - calcium phosphate ) Powder manufacturing

After measuring 400 ml of ethanol with a measuring cylinder, put it in a container of 500 ~ 1000ml size, put about 200ml volume of zirconia balls into this container, add 50 ~ 60g of HA and 50 ~ 60g of Beta-TCP.

At this time, since HA and beta-TCP are powder, shake enough, and if ethanol is insufficient, supplement about 30 ~ 50ml.

Ball undergoes 24 to 30 hours of ball mill process 200 ~ 400rpm in pushing (ball mill).

After ball milling, the mixed solution is transferred to a tray and dried in a dry oven at 60 ± 10 ° C for about 3 to 5 hours.

Dry at room temperature for 12 to 15 hours.

This drying condition is to completely submerge the residual ethanol.

After the ethanol is completely dried, it is placed in an alumina crucible for calcination treatment.

After that, it is put into the furnace and calcined.

In this case, the condition of the calcination treatment is adjusted by increasing the temperature of the FURNACE at 5 to 10 degrees per minute, increasing the temperature for 90 to 180 minutes to 900 degrees, maintaining the temperature for about 180 to 240 minutes, After about 8 to 9 hours, it can be removed from the printer.

When the calcined powder is stood at 200 mu m, the production of the BCP powder is completed.

Optionally, a silk fiber mesh ( silk) microfibril mesh ) and PCL (polycaprolactone) may be added.

2. BCP slurry Manufacturing

150 to 200 ml of ethanol was added to a 300 ml volume of a glass bottle and then 6 to 10 g of polyvinyl butyral-co-vinyl alcohol-co-vinyl acetate (PVB) was added thereto while stirring with a magnetic stirrer at a speed of 200 to 300 rpm After stirring slowly, agitate for about 6 ~ 10 hours to confirm that PVB is completely dissolved in ethanol.

If PVB is dissolved, add 6 ~ 10g of TEP (triethylphosphate, 99.8% Sigma Aldrich) to the solution, add 30g of BCP powder and 0.3g of silk and stir thoroughly for about one week to prepare BCP slurry.

The prepared BCP slurry was coated on a cube block having a plurality of through holes and sintered in an electric furnace at 1250 DEG C to form a bone matrix having a plurality of through holes 11 as shown in Fig. (bone matrix).

Claims

A method of manufacturing a bone graft material,
After the zirconia balls in ethanol into one-half volume of ethanol, hydroxyapatite _{(Ca 10 (PO 4) 6} (OH) 2, hydroxyapatite; HA) and beta-tri calcium phosphate: the same (beta -TCP β-Tricalcium Phosphate) Mixing in a weight ratio;
Placing the mixed solution in a ball mill and performing a ball milling process at a rotation speed of 200 to 400 rpm for 24 to 30 hours;
Holding the mixed solution having passed through the ball milling process in a size of 325 mesh;
Drying the mixed solution at 60 ± 10 ° C. for 3 to 5 hours in a dry oven, and then drying at room temperature for 12 to 15 hours to completely remove ethanol;
The dried mixture was placed in an alumina vessel, and the temperature of the electric furnace was adjusted at 5 to 10 ° C per minute. The temperature was raised for 90 to 180 minutes, heated to 900 ° C, held for 180 to 240 minutes, Followed by calcination treatment in an electric furnace after 8 to 9 hours;
Preparing a Bi-calcium phosphate (BCP ) powder having a particle size of 200 mu m after the calcination;
(PVB) was added to a container filled with ethanol and the PVB was dissolved completely while stirring the poly- (vinyl-butyral-co-vinyl alcohol-co-vinyl acetate Triethylphosphate ( TEP ) was added at the same weight ratio as PVB, and 5 parts by weight of silk fibers were added to PVB. The prepared BCP powders were mixed at a weight ratio of 5 times with respect to PVB and stirred for one week Preparing a BCP slurry; and
Coating the prepared BCP slurry on a cube formed of a soft material of wood or carbon black and forming a plurality of through holes and then sintering the mixture in an electric furnace at 1,250 DEG C to prepare a bone graft material block Gt;

delete

The method according to claim 1,
Wherein the pore size of the plurality of through holes formed in the bone graft material is adjusted to 150 to 850 탆.

The method according to claim 1,
Wherein the BCP powder comprises at least one of silk microfibril mesh and polycaprolactone (PCL) in the step of preparing the BCP powder.

The method according to claim 1,
Wherein the bone graft material block forms a bone matrix forming a network of each channel.