KR101199929B1 - Method of producing artificial bone and artificial bone made thereby - Google Patents

Abstract

The present invention relates to a method for producing artificial bone and an artificial bone produced thereby.
The present invention is to prepare a support of zirconia and non-facial calcium phosphate using a polyurethane sponge to mimic the spongy bone, and to mimic the harborian structure by wrapping the fibers produced by electrospinning on the wire to mimic the dense bone, After the fibers are wrapped with a bundle of fibers, the fibers can be wrapped again to mimic the austenite structure to produce spongy bone and dense bone of natural bone.

Description

Method of producing artificial bone and artificial bone produced thereby

The present invention relates to a method for producing artificial bone by sponge replication and electrospinning process and to artificial bone produced by the same, and more particularly, to zirconia and non-facial calcium phosphate (ZrO) using a polyurethane sponge to mimic spongy bone. ₂ / BCP) to support, mimic the Habersian structure by wrapping the fibers produced by electrospinning to the wire to mimic the dense bone, and then constituting the bundle of fibers wrapped with fibers and then wrapping the fibers again to austene The present invention relates to a method for producing artificial bones by sponge replication and electrospinning processes that can produce spongy bones and dense bones of natural bones by mimicking the structure, and artificial bones produced thereby.

In general, the mimetic approach of grafting agents has recently gained attention. Porous materials are always used to treat natural bone, but none of them takes into account natural bone with fine microstructure, which depends on the natural bone regeneration process.

An appropriate approach with the ability to naturally reproduce a structure that mimics natural bone is an interesting approach.

Sponge cloning is already well known for mimicking spongy bone structure. Electrospinning, on the other hand, is mostly used as a tissue engineering scaffold as a polymer material. Electrospun mats are interconnected porous structures and can be manufactured in various forms.

As is well known, natural bone consists of spongy bone and dense bone.

At present, research on the manufacture of artificial bones is mainly focused on the cancellous bone.

Dense bone is usually composed of Habersian channels, Bokman channels and austenone structures and has a complex structure from nano to micro units.

Many prior patents on artificial bone have been proposed, and as an example, Korean Patent No. 0985154 discloses a method for preparing a porous support using a urethane foaming method.

However, while many studies on artificial bones have been made, there are still differences from natural bones, and in particular, there is still a problem that mimics the complex and detailed structure of dense bones.

An object of the present invention is to solve the problems of the prior art, the production of artificial bones to replace the finger bones or toes by manufacturing artificial bones mimicking the structure of the spongy bone and dense bone constituting the bone It relates to a method and an artificial bone produced thereby.

In order to achieve the above object of the present invention, the artificial bone manufacturing method according to the present invention,

For mimicking spongy bone,

Step 1a (S1a) of immersing and coating a polyurethane sponge in the zirconia slurry; Step 1b of preparing a zirconia support by sintering the coated polyurethane sponge (S1b); Step 1c (S1c) of preparing a zirconia / non-basic calcium phosphate and a zirconia / non-basic calcium phosphate support having a three-layer structure by coating the zirconia support by dipping the non-facial calcium phosphate and the zirconia mixed slurry; Step 1d (S1d) of dipping the zirconia / non-pic calcium phosphate and the zirconia / non-pic calcium phosphate support back into the non-facial calcium phosphate slurry; Step 1e (S1e) of preparing a support of zirconia and non-pic calcium phosphate (ZrO ₂ / BCP) by sintering the coated zirconia / non-pic calcium phosphate and zirconia / non-pic calcium phosphate support in step 1d (S1d) );

To mimic the Habersian structure of dense bone,

Step 2a (S2a) of dissolving polymethyl methacrylate and polycaprolactone in nitromethane and acetone; Step 2b of mixing the hydroxyapatite powder in a mixed solution of the polymethyl methacrylate and polycaprolactone solution (S2b); Step 2c of applying a voltage to a mixed solution of polymethyl methacrylate / polycaprolactone / hydroxyapatite mixed with the hydroxyapatite powder to produce a mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite ( S2c); 2d step (S2d) of winding the mixed fiber of the produced polymethyl methacrylate / polycaprolactone / hydroxyapatite on a wire; The polymethyl methacrylate / polycaprolactone / hydride on the outer surface of the zirconia and non-facial calcium phosphate prepared in step S1e, surrounding the wire structure wound around the mixed fiber prepared in step S2d Wrapping the mixed fibers of roxiapatite; And removing a wire from the structure to produce a mimic that mimics a hollow austenone structure.

According to the present invention, it is possible to obtain a support of zirconia and non-facial calcium phosphate mimicking the sponge bone by sponge cloning, and to obtain dense bone mimicking the Haversian channel and the Osteon structure by electrospinning. The artificial bone produced by the combination of the two methods can be applied to the finger or toe bone because it is similar to natural bone.

1 is a flow chart for the 'A process' of the artificial bone manufacturing method according to the present invention,
Figure 2 is a photograph and a scanning electron microscope image of the 'zirconia and non-facial calcium phosphate support (ZrO ₂ / BCP) prepared by the process A of the present invention,
3 is a flow chart for the 'B process' of the artificial bone manufacturing method according to the present invention,
Figure 4 shows a photograph and EDS results showing the 'support of zirconia and non-facial calcium phosphate' prepared by the method for producing artificial bone according to the present invention.
Figure 5 is a graph showing the XRD results of the 'support (a) of the zirconia and non-facial calcium phosphate (a)' and 'PMMA / PCL fiber (b) containing the HAp' prepared by the method for preparing artificial bone according to the present invention;
Figure 6 is a graph showing the results of the FT-IR analysis of artificial bones according to the present invention,
Figure 7 is a photograph sequentially showing a process A, process B, process C in the manufacturing method of artificial bone according to the present invention,
8 is a process chart showing step by step the manufacturing method of artificial bone according to the present invention.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Method for producing artificial bone according to the present invention A process for producing a sponge bone mimics using a sponge replication method largely; A step B of preparing a dense bone mimetic using an electrospinning method; Comprising C process for producing artificial bone by combining the spongy bone mimic of step A and the dense bone mimic of step B.

Hereinafter, the above steps will be described in more detail.

A process

1 is a flow chart for the 'A process' of the method of manufacturing artificial bone according to the present invention.

As shown in Figure 1 and 8, the 'A process' of the artificial bone production method according to the present invention, 5wt% polyvinyl butyral (PVB) and 10wt% zirconia powder is mixed with zirconia (ZrO ₂ ) step 1a of dipping the polyurethane sponge in the slurry to coat (S1a); Step 1b of preparing a zirconia support by sintering the coated polyurethane sponge at 1,400 ~ 1,700 ℃ in a microwave furnace (S1b); The zirconia support is immersed in a mixed slurry of biphasic calcium phosphate (BCP) and zirconia, and coated to provide a support having a three-layer structure of zirconia / non-pic calcium phosphate and zirconia / non-pic calcium phosphate. Step 1c to prepare (S1c); Step 1d (S1d) of dipping the support of the zirconia / non-pic calcium phosphate and the support of zirconia / non-pic calcium phosphate in the non-facial calcium phosphate slurry; Supports of zirconia and non-facial calcium phosphate (ZrO ₂ / BCP) by sintering the coated zirconia / non-facial calcium phosphate and the support of zirconia / non-facial calcium phosphate at 1,400 ~ 1,700 ℃ in a microwave furnace It is configured to include a step 1e (S1e) to manufacture.

Figure 2 is a photograph and a scanning electron microscope image of the 'support of zirconia and non-facial calcium phosphate' prepared by step A of the present invention.

As shown in (a) and (b) of FIG. 2, the support of Zirconia and non-facial calcium phosphate (ZrO ₂ / BCP) is a cylindrical shape having a diameter of 4 mm and has a shape similar to that of the sponges with interconnected porous structures. It can be seen that it is implemented.

(C) and (d) of FIG. 2 show surface enlarged photographs and cross-sectional photographs of supports of zirconia and non-facial calcium phosphate, respectively.

As shown in FIG. 2C, many pores were observed on the surface. And as shown in (d) and (e1), (e2), (e3) of Figure 2, the cross section of the zirconia and non-facial calcium phosphate support is zirconia, zirconia and non-facial calcium phosphate, non-facial calcium phosphate 3 It can be seen that it consists of two layers.

B process

Figure 3 is a flow chart for the 'B process' of the artificial bone manufacturing method according to the present invention.

As shown in Figure 3, 'B process' of the artificial bone production method according to the present invention, 20 wt% polymethyl methacrylate (PMMA: polymethyl methacrylate) and 10 wt% polycaprolactone (PCL: poly- step 2a (S2a) of dissolving caprolactone in nitromethane and acetone; Step 2b (S2b) of mixing 30 wt% hydroxyapatite (HAp) powder with a solution of the polymethyl methacrylate (PMMA) and polycaprolactone (PCL) solution; A voltage is applied to a mixed solution of polymethyl methacrylate / polycaprolactone / hydroxyapatite mixed with the hydroxyapatite (HAp) powder to produce a mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite. Step 2c (S2c); It comprises a 2d step (S2d) of winding the mixed fiber of the polymethyl methacrylate / polycaprolactone / hydroxyapatite produced on the wire.

Step B is modified to mimic the Habersian structure and the austenone structure of natural bone.

In other words, in order to produce a Haberian structure mimic, the steps 2a to 2c are performed, and the wire is selected to have a diameter of about 0.2 mm to 0.4 mm.

The process for mimicking an austene structure is mentioned later.

On the other hand, Figure 4 shows a photograph and EDS results showing the 'support of zirconia and non-facial calcium phosphate' prepared by the method for producing artificial bone according to the present invention.

4 (a) is a scanning electron micrograph showing that the mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite well wrapped the support of zirconia and non-facial calcium phosphate. The mixed fiber of acrylate / polycaprolactone / hydroxyapatite had a diameter of about 2 μm.

4B shows hydroxyapatite (HAp) in the mixed fiber (PMMA / PCL) of polymethyl methacrylate / polycaprolactone as a result of EDS.

That is, the support of zirconia and non-facial calcium phosphate was wrapped with a mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite by electrospinning, and the hydroxyapatite powder was mixed with a mixed powder of methacrylate / polycaprolactone. Loaded.

* Hydroxyapatite can accelerate bone formation due to excellent bone conductivity.

C process

On the other hand, as shown in Figure 8 in order to mimic the auson structure, the zirconia / non-facial calcium phosphate support (1) prepared in the step A to the Haberian structure mimic (5) prepared in the step B 8 After surrounding the dog, the outer surface is wrapped with the mixed fiber 2 of polymethyl methacrylate / polycaprolactone / hydroxyapatite.

After the wire 3 is removed, a mimic 5 that mimics a hollow austenone structure is produced.

This manufacturing process will be described in detail later in the process.

5 is a mixed fiber of polymethyl methacrylate / polycaprolactone containing 'a support of zirconia and non-facial calcium phosphate (a)' and 'hydroxyapatite prepared by the method for preparing artificial bone according to the present invention. b) is a graph showing the XRD results.

The x axis is the energy of the beam (2 theta degree), and the y axis is the intensity of the beam.

As shown in (a) of FIG. 5, the peaks of zirconia, hydroxyapatite and α-TCP were shown in XRD of the zirconia and the non-facial calcium phosphate support.

It was found that the β-TCP peak in the non-facial calcium phosphate initial material was changed to α-TCP due to high temperature sintering.

On the other hand, as shown in (b) of FIG. 5, the mixed solution of hydroxyapatite-containing polymethyl methacrylate / polycaprolactone (PMMA / PCL) was found to coincide with the peaks of the starting materials at each peak without phase change. I could confirm

Figure 6 is a graph showing the results of the FT-IR analysis of artificial bone according to the present invention.

Referring to FIG. 6, it was also confirmed in the FT-IR analysis that the hydroxyapatite powder was successfully added to the polymethyl methacrylate / polycaprolactone fiber.

The mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite was consistent with the polymethyl methacrylate and polycaprolactone peaks (see (b, c, d) of FIG. 6) and the hydroxyapatite peak was 563. cm ^- it was found in ^one

On the other hand, Figure 7 is a photograph showing a step A, B, C process in sequence in the method of manufacturing artificial bone according to the present invention, Figure 8 is a process diagram showing a step of a method of manufacturing artificial bone according to the present invention.

As shown in (step2) of FIG. 8, the wire 3 having a thickness of 300 μm is wrapped with a mixed fiber 2 of polymethyl methacrylate / polycaprolactone / hydroxyapatite by electrospinning to mimic a Harshian structure 4. Make

Then, as shown in Fig. 7 (b) and Fig. 8 (step3), the eight Haberian mimetics (4) were collected and the mixing ratio of polymethyl methacrylate / polycaprolactone was 3: 7. It is firmly wrapped again with a mixed fiber (2) of one polymethyl methacrylate / polycaprolactone / hydroxyapatite to form an austeric structure (5).

Subsequently, as shown in FIGS. 7A and 8, and step 8 of FIG. 8, the mimic body 5 having eight asteron structures is surrounded by the support 1 of zirconia and non-facial calcium phosphate obtained in step A. After that, it is wrapped again with a mixed fiber (2) of polymethyl methacrylate / polycaprolactone / hydroxyapatite by electrospinning.

Thereafter, as shown in (e) and (step 5) of FIG. 7, the wire 3 was finally removed to form a hollow structure, and the diameter of the final support 6 was 12 mm.

Although the present invention has been described in connection with the above-mentioned preferred embodiments, it will be apparent to those skilled in the art that various modifications and variations can be made without departing from the spirit and scope of the invention, It is obvious that the claims fall within the scope of the claims.

1: support of zirconia and non-facial calcium phosphate
2: mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite
3: wire
4: Mimic of the Habersian structure
5: mimetic of the asteron structure

Claims (1)

For mimicking spongy bone,
Step 1a (S1a) of immersing and coating a polyurethane sponge in the zirconia slurry;
Step 1b of preparing a zirconia support by sintering the coated polyurethane sponge (S1b);
Step 1c (S1c) of preparing a zirconia / non-basic calcium phosphate and a zirconia / non-basic calcium phosphate support having a three-layer structure by coating the zirconia support by dipping the non-facial calcium phosphate and the zirconia mixed slurry;
Step 1d (S1d) of dipping the zirconia / non-pic calcium phosphate and the zirconia / non-pic calcium phosphate support back into the non-facial calcium phosphate slurry;
Step 1e (S1e) of preparing a support of zirconia and non-pic calcium phosphate (ZrO ₂ / BCP) by sintering the coated zirconia / non-pic calcium phosphate and zirconia / non-pic calcium phosphate support in step 1d (S1d) );
To mimic the Habersian structure of dense bone,
Step 2a (S2a) of dissolving polymethyl methacrylate and polycaprolactone in nitromethane and acetone;
Step 2b of mixing the hydroxyapatite powder in a mixed solution of the polymethyl methacrylate and polycaprolactone solution (S2b);
Step 2c of applying a voltage to a mixed solution of polymethyl methacrylate / polycaprolactone / hydroxyapatite mixed with the hydroxyapatite powder to produce a mixed fiber of polymethyl methacrylate / polycaprolactone / hydroxyapatite ( S2c);
2d step (S2d) of winding the mixed fiber of the produced polymethyl methacrylate / polycaprolactone / hydroxyapatite on a wire;
The polymethyl methacrylate / polycaprolactone / hydride on the outer surface of the zirconia and non-facial calcium phosphate prepared in step S1e, surrounding the wire structure wound around the mixed fiber prepared in step S2d Wrapping the mixed fibers of roxiapatite; And
Removing the wire in the structure manufacturing method of artificial bones, characterized in that to produce a mimic that mimics the hollow austenone structure.

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