JP2003319954A - Method of manufacturing biological tissue anaplerotic body and surgical operation method using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of manufacturing biological tissue anaplerotic body with which a precious cell is imparted without waste, and a surgical operation method using biological tissue anaplerotic body. <P>SOLUTION: While covering an inner surface of a container 1 with granular bone anaplerotic body 2A, a cell containing liquid which contains a desired cell is sprayed over block-like bone anaplerotic body 2B placed within the container 1 to obtain the block-like bone anaplerotic body and the granular bone anaplerotic body. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a biological tissue filling body used for regenerating a living tissue defective portion such as a bone defect portion and a surgical method using the living tissue filling body.

[0002]

2. Description of the Related Art In recent years, a living tissue such as a bone has been regenerated by filling a living tissue defect such as a bone defect caused by excision of a bone tumor or trauma with a living tissue repair material such as a bone filling material. It has become possible to repair bone defects and the like.
For example, hydroxyapatite (HAP) and tricalcium phosphate (TCP) are known as bone filling materials, but β-
A scaffold composed of a calcium phosphate porous body such as TCP is used. When this β-TCP is brought into contact with the bone cells of the bone defect portion, so-called remodeling is performed by the osteoclasts and osteoblasts, and the bone substitute material filled in the bone defect portion is autologous with time. It is replaced by bone.

By the way, in order to increase the speed of repair of a bone defect site after surgery, instead of using the bone prosthetic material as it is, the bone marrow fluid collected from a patient is applied to the bone prosthetic material to compensate the bone defect site. Is being done. In this case, the bone marrow fluid is extracted from the patient, the bone filling material is immersed in this bone marrow fluid, and then the bone defect is filled.

[0004]

However, in the method of simply immersing the bone filling material in the bone marrow fluid, there is a large loss due to the flow-out after the immersion, and the cell-containing fluid containing the desired cells required is sufficiently added. There is a problem that it cannot be attached. Further, it is necessary to use a valuable cell-containing liquid containing desired cells as little as possible. Therefore, the present invention provides a method for producing a biological tissue filling body, which allows precious cells to be added without waste.

[0005]

In order to solve the above-mentioned problems, the invention described in claim 1 provides a granular body tissue filling material (for example, the embodiment) in which the inner surface of the container (for example, the container 1 in the embodiment) is granular. In the state of being covered with the bone filling material 2A), the block-shaped living tissue filling material (for example, the bone filling material 2B in the embodiment) placed in the container is sprayed with a liquid containing cells and / or a growth promoting substance. , A block-shaped biological tissue filler (for example, the bone filler 20 in the embodiment).
B) and a granular body tissue filler (for example, bone filler 20A in the embodiment) are obtained. With such a configuration, when a block-shaped body tissue filler to be loaded into an affected area is manufactured, granular body tissue without wasting the cells and / or growth promoting substance-containing liquid scattered around Since it becomes possible to attach to a filling material, when loading a block-shaped living tissue filling body on the affected area, the surrounding space is filled with granular living tissue filling containing cells and / or a growth promoting substance-containing liquid. Can be filled with the body.

According to the second aspect of the present invention, the granular body tissue supplement adhered to the inner surface of the container is collected and wrapped with a bioabsorbable sheet (for example, the sheet 5 in the embodiment) to obtain a body tissue supplement. Is characterized by. With such a configuration, it is possible to manufacture a body tissue filler which can be freely changed in shape and has no problem in terms of biocompatibility.

According to a third aspect of the present invention, a granular biological tissue filling material is arranged on the surface of the bioabsorbable sheet (for example, the sheet 15 in the embodiment), and the liquid containing cells and / or growth promoting substance is added to the biological tissue. It is characterized in that it is sprayed on a filling material, and the living tissue filling body to which cells are attached is wrapped with the above-mentioned sheet to obtain a living tissue filling body. With such a configuration, the cells can be sufficiently attached to the tissue filling material, the shape of the cells can be freely changed with the cells attached, and there is no problem in terms of biocompatibility. A filler can be manufactured.

According to a fourth aspect of the invention, a liquid containing cells and / or a growth promoting substance is attached to the surface of the bioabsorbable sheet,
This sheet is characterized in that a block-shaped living tissue filling material is wrapped to obtain a living tissue filling. With this configuration, the cells and / or the growth promoting substance-containing liquid can be uniformly attached to the periphery of the biological tissue filling material without waste.

According to a fifth aspect of the present invention, after a cell and / or growth promoting substance-containing liquid is attached to the biological tissue filling material,
Further, a liquid containing cells and / or a growth promoting substance is sprayed to obtain a body tissue filling material. With this configuration, the cells can be sufficiently adapted to the biological tissue filling material. The invention described in claim 6 is characterized in that the living tissue defect portion is filled with a living tissue filling body using a block-shaped living tissue filling body and a granular living tissue filling body. With this configuration, it is possible to flexibly adapt to the shape of the defective portion. The invention described in claim 7 is characterized in that a living tissue filling containing at least a granular living tissue filling is wrapped with a bioabsorbable sheet to fill the living tissue defect. With this configuration, it is easy to match the size and shape of the defective portion and the granules do not spill.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 shows a method for manufacturing a biological tissue filling body according to the first embodiment of the present invention, specifically, a bone filling body. First, the inner surface of the container 1 is covered with a granular bone filling material 2A. Here, the container 1 has an open upper part, and a biocompatible adhesive material 3 such as fibrin glue (not shown) is applied to the inner surface of the container 1 and the granular bone filling material is inserted through the biocompatible adhesive material 3. Material 2A is attached. Bone filling material 2A
Is manufactured by the method (mechanochemical method) disclosed in Japanese Patent No. 2597355, is formed into granules, and is provided with a cell-containing liquid containing desired cells, and then a living tissue defect portion, specifically, a bone defect. It is used to fill the part. Its main component is β-TCP (beta tricalcium phosphate), which is a porous biocompatible material, and many pores are formed inside.

Next, a block-shaped bone filling material 2 is placed in the container 1.
B is placed and a cell-containing solution containing desired cells is sprayed by the nozzle 4. Here, the cell-containing liquid containing the desired cells is obtained by diluting a concentrated liquid containing mesenchymal stem cells and the like while removing unnecessary components from the bone marrow fluid. Specifically, it is diluted with physiological saline to such an extent that spraying is not hindered. As a method for obtaining the concentrated liquid, a known centrifugal separator, immunomagnetic cell separator or flow cytometry may be used. When the cell-containing liquid is sprayed on the block-shaped bone filling material 2B in this manner, the sprayed liquid is scattered in the container 1, but the scattered cell-containing liquid is attached to the granular bone filling material 2A on the inner surface of the container 1. Therefore, the cells are used without waste. In addition, BMP, FGF, TGF-β, IGF, EGF, V
You may spray the containing liquid containing the substance which promotes growth, such as EGF, HGF, and a cytokine. As a result, a bone prosthetic material, which is a bone prosthetic material to which cells and / or growth promoting substances are attached by one-time application, more specifically, a block-shaped bone prosthetic material 20B.
It is possible to obtain a granular bone filling material 20A. According to this embodiment, when the block-shaped bone prosthesis 20B to be loaded on the affected area is manufactured, the cell-containing liquid scattered around the prosthesis can be attached to the granular bone prosthesis 2A, which is valuable. Cells can be used without waste.

Then, these block-shaped bone substitutes 20
In the case of using B and the granular bone substitute 20A, as shown in FIG.
As shown in, the block-shaped bone filling body 20B can be loaded in the affected area, and the granular bone filling body 20A can be filled in the gaps in the affected area. In addition, the granular bone filling material 20A collected from the inner surface of the container 1 is wrapped in a bioabsorbable sheet, for example, a sheet 5 made of a biodegradable polymer, or the sheet 5 used in place of the container 1 is used for granulation. It is possible to manufacture and envelop a bone-shaped bone prosthesis 20A in the shape of a block, and to form a shape so that it can be filled into the space around the block-shaped bone prosthesis 20B as shown in FIG. By doing so, when the block-shaped bone filling body 20B is loaded into the affected area, the space around the bone filling body 20B is a granular bone filling body 2 containing the cell-containing liquid.
Since it can be filled with 0 A, precious cells can be used without waste in that respect as well.

FIG. 4 shows a method for manufacturing a bone prosthesis according to the second embodiment of the present invention. First, a granular bone filling material 2A is placed on the surface of a bioabsorbable sheet, for example, a sheet 15 made of a biodegradable polymer. Next, the same cell-containing liquid as that of the above-described embodiment is sprayed on the bone filling material 2A by the nozzle 4, and the bone filling material 2A to which the cells are attached is formed on the sheet 15.
And a granular bone filling body 20A is obtained. And
As shown in FIG. 5, the bone filling body 2 wrapped with the sheet 15
The shape may be adjusted according to 0A to the bone defect part of the affected part.
According to this embodiment, since the bone prosthesis 20A whose shape can be freely changed and has no problem in terms of biocompatibility can be manufactured, the filling flexibility can be increased regardless of the shape of the loading site.

FIG. 6 shows a method for manufacturing a bone prosthesis according to the third embodiment of the present invention. First, a bioabsorbable sheet, for example, the surface of the biodegradable polymer sheet 15 is attached with the same cell-containing liquid as in the above-described embodiment containing desired cells. Specifically, prior to the attachment work, the cell-containing liquid containing the desired cells is diluted with physiological saline so as to have an appropriate viscosity, and the syringe 9 is composed of a syringe 6, a piston 7 and a needle 8. Put it in. Then, as shown in FIG. 6, the cell-containing liquid is uniformly attached on the surface of the sheet 15 while the injector 9 is meandering. Next, as shown in FIG. 7, the block-shaped bone filling material 2B is placed on the sheet 15, and the bone filling material 2B is wrapped with the sheet 15 as shown in FIG. 8 to obtain the bone filling body 20B. According to this embodiment, since the cell-containing liquid can be uniformly attached to the periphery of the bone prosthetic material 2B without waste, a homogeneous bone prosthetic material 20B can be manufactured.

FIG. 9 shows a method for manufacturing a bone prosthesis according to the fourth embodiment of the present invention. In this manufacturing method, the cell-containing liquid similar to that of the above-described embodiment is attached to each surface of the block-shaped bone prosthesis 2B using the syringe 9 having the same configuration as that of the above-described embodiment, and then the cell-containing liquid is further added to the bone. The bone filling body 20A is obtained by spraying the entire surface of the filling material 2A with the nozzle 4. According to this embodiment, the cells containing the desired cells can be sufficiently adapted to the bone filling body 20A, so that the bone filling body 20A to which the desired cells are reliably attached can be obtained.

The present invention is not limited to the above-described embodiment, but in the above-described embodiment, the bone filling material has been described as an example of the living tissue filling material. However, other than that, the present invention is applied to muscles, teeth, and various organs. can do. Further, the sheets 5 and 15 may be reticulated. The cells contained may be ES cells or other tissue stem cells other than mesenchymal stem cells, and various cells such as bone cells, osteoblasts, osteoclasts, nerve cells, chondrocytes. In addition, the liquid contained is BMP, FGF, TGF-β, IGF, EG.
A substance that promotes growth such as F, VEGF, HGF and cytokine may be contained.

[0017]

As described above, according to the invention described in claim 1, when a block-shaped body tissue filling body to be loaded in an affected area is manufactured, the cell-containing liquid scattered around the body-containing body tissue Can be attached to a granular living tissue filling material, and when a block-shaped living tissue filling material is loaded into the affected area, the space around it is filled with a granular living tissue filling material containing a cell-containing liquid. As a result, valuable cells can be used without waste.

According to the second aspect of the present invention, since the body tissue filling body can be freely changed in shape and has no problem in terms of biocompatibility, a filling degree of freedom can be obtained regardless of the shape of the loading site. There is an effect that can be increased.

According to the third aspect of the present invention, the cells can be sufficiently attached to the biological tissue filling material, and the shape of the cells can be freely changed in the state where the cells are attached and the biocompatibility is pointed out. Since it is possible to produce a living tissue filling without any problem, there is an effect that the filling degree of the living tissue filling with cells sufficiently adhered can be increased regardless of the shape of the loading site.

According to the invention described in claim 4, since the cell-containing liquid can be uniformly attached to the periphery of the biological tissue filling material without waste, a homogeneous biological tissue filling body can be manufactured. effective.

According to the invention described in claim 5, the cells can be sufficiently adapted to the biological tissue filling material.
There is an effect that it is possible to surely obtain a biological tissue filling material to which cells are attached. According to the invention described in claim 6, there is an effect that the shape of the defective portion can be flexibly dealt with. According to the invention described in claim 7, there is an effect that it is easy to match the size and shape of the defective portion and the granules do not spill.

[Brief description of drawings]

FIG. 1 is a perspective view showing a manufacturing method according to a first embodiment of the present invention.

FIG. 2 is an explanatory diagram showing a loading shape according to the first embodiment.

FIG. 3 is an explanatory view showing another loading shape of the first embodiment.

FIG. 4 is a perspective view showing the manufacturing method of the second embodiment of the present invention.

FIG. 5 is an explanatory view showing a loading shape of the second embodiment.

FIG. 6 is a perspective view showing a manufacturing process of the third embodiment of the present invention.

FIG. 7 is a perspective view showing a manufacturing process of the third embodiment.

FIG. 8 is a perspective view showing a manufacturing process of the third embodiment.

FIG. 9 is a perspective view showing the manufacturing method of the fourth embodiment of the present invention.

[Explanation of symbols]

1 container 2A, 2B bone filling material (living tissue filling material) 5,15 sheets 20A, 20B Bone filling body (living tissue filling body)

Continued front page    (72) Inventor Hideyuki Adachi             2-43 Hatagaya, Shibuya-ku, Tokyo Ori             Inside Npus Optical Industry Co., Ltd. F term (reference) 4C081 AB04 BA12 CD27 CD34 DA01                       DA11 EA06                 4C097 AA01 BB07 CC03 DD07 DD15

Claims (7)

[Claims] 1. A cell- and / or growth-promoting substance-containing liquid is sprayed onto a block-shaped living tissue filling material placed in the container with the inner surface of the container covered with a granular living tissue filling material,
A method for producing a body tissue filler, which comprises obtaining a block-shaped body tissue filler and a granular body tissue filler. 2. The method for producing a biological tissue filling body according to claim 1, wherein the granular biological tissue filling body attached to the inner surface of the container is collected and wrapped with a bioabsorbable sheet to obtain a biological tissue filling body. . 3. A biological tissue filling material in the form of granules is arranged on the surface of a bioabsorbable sheet, cells and / or growth promoting substance-containing liquid is sprayed on the biological tissue filling material, and the sheet is filled with living tissue filling cells. A method for producing a biological tissue filling body, which comprises wrapping a body to obtain a biological tissue filling body. 4. A biological tissue supplementer characterized in that a liquid containing cells and / or a growth promoting substance is adhered to the surface of a bioabsorbable sheet, and a block-like biological tissue supplementary material is wrapped with this sheet to obtain a biological tissue supplement. Body manufacturing method. 5. A biological tissue filling material is obtained by adhering a liquid containing cells and / or a growth promoting substance to a biological tissue filling material, and further spraying the liquid containing cells and / or a growth promoting substance to obtain a biological tissue filling body. Method for manufacturing filler. 6. A surgical method using a living tissue filling body, comprising filling a living tissue filling body using a block-shaped living tissue filling body and a granular living tissue filling body in a living tissue defective portion. 7. A surgical method using a body tissue filling body, which comprises wrapping a body tissue filling body containing at least a granular body tissue filling body with a bioabsorbable sheet and filling the living body tissue defect.