JP2003319953A - Method, container, and apparatus of manufacturing biological tissue anaplerotic body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for manufacturing biological tissue anaplerotic body, a container for manufacturing and a manufacturing apparatus in which a cell is sufficiently penetrated to the inside even within a limited time. <P>SOLUTION: In the method for forming biological tissue anaplerotic body 10 with which a portion lacked with biological tissue is generated by penetrating a cell 17 into the porous biological tissue anaplerotic body 11, the biological tissue anaplerotic body 11 and the cell 17 are led into a container 12 for manufacturing and a centrifugal force is applied thereto. <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 body tissue filling body used for regenerating a body tissue defect portion, a vessel for producing the body tissue, and a production apparatus.

[0002]

2. Description of the Related Art In recent years, it has become possible to regenerate bone and repair the bone defect portion by filling the bone defect portion caused by excision of bone tumor, trauma or the like with a bone substitute material.
Hydroxyapatite (HAP) as bone filling material
And tricalcium phosphate (TCP) are known, but from the idea that no foreign matter remains in the body, for example, a scaffolding material composed of a calcium phosphate porous body such as β-tricalcium phosphate (hereinafter β-TCP). Is used. β-TC
When P is brought into contact with the bone cells of the bone defect portion, so-called remodeling is performed in which osteoclasts eat β-TCP and osteoblasts form new bone. That is, the bone filling material filled in the bone defect portion is replaced with autogenous bone over time.

By the way, in order to increase the speed of repair of a bone defect portion after surgery, it is possible to fill the bone defect portion by immersing the bone filler material in the bone marrow fluid collected from the patient, instead of using the bone filler material as it is. Has been done.

[0004]

In this case, the cells are extracted from the patient, the bone filling material is immersed in the cells, and then the bone filling portion is filled with the bone filling material. However, there is a problem that simply immersing the bone prosthetic material in the cells does not allow the cells to sufficiently penetrate into the bone prosthetic material within a limited time during the operation.

[0005] Therefore, an object of the present invention is to provide a method for producing a biological tissue filling body, a production container and a production apparatus capable of sufficiently permeating cells to the inside even within a limited time.

[0006]

In order to achieve the above object, the invention according to claim 1 is a biological tissue to be filled in a defective portion of a biological tissue by permeating cells into a porous biological tissue filling material. A method for producing a biological tissue filling body that forms a filling body, characterized by introducing the living tissue filling material and the cells into a manufacturing container and applying a centrifugal force.

[0007] Thus, when the living tissue filling material and the cells are introduced into the manufacturing container and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force.

The invention according to claim 2 is, in the invention according to claim 1, characterized in that a granular material is used as the biological tissue filling material.

As described above, since the biological tissue filling material is in the form of granules, the surface area is increased and the cells can be efficiently permeated into the biological tissue filling material, and at the same time, the cells are brought into contact with each other on the surface of the biological tissue filling material. I can do a lot.

The invention according to claim 3 relates to the invention according to claim 2, characterized in that the granular biological tissue filling material is blended so as to have substantially the same density as the cells.

As described above, since the granular biological tissue filling material is blended so as to have substantially the same density as the cells, the living tissue filling material and the cells can be mixed evenly by the centrifugal force. Can be more efficiently permeated into the biological tissue filling material.

The invention according to claim 4 is a method for producing a biological tissue filling body, which comprises forming a living tissue filling body to be filled in a living tissue defective portion by infiltrating cells into a porous living tissue filling material. The living tissue filling material is formed into a tubular shape, and the cells are introduced into the tubular living tissue filling material to impart a centrifugal force to the living tissue filling material.

Thus, when cells are introduced into the tubular tissue filling material and a centrifugal force is applied to the tissue filling material, the cells are forcibly permeated into the tissue filling material by the centrifugal force. . Moreover, since the living tissue filling material is formed in a container shape and cells are directly injected, the container is not required.

The invention according to claim 5 relates to the invention according to claim 4, wherein a granular living tissue filling material is introduced inside the tubular living tissue filling material together with the cells into the tubular living tissue filling material. The feature is that centrifugal force is applied to the filling material.

As a result, when cells and granular living tissue filling material are introduced into the tubular living tissue filling material and centrifugal force is applied to the living tissue filling material, the tubular living tissue filling material is centrifugally loaded. The cells are forcibly permeated inside the material, and the cells are also forcibly permeated by the centrifugal force into the granular biological tissue filling material. Moreover, since the granular living tissue filling material is put into the tubular living tissue filling material, the space inside the tubular living tissue filling material can be reduced.

According to a sixth aspect of the present invention, a porous biological tissue filling material and cells are introduced, and a centrifugal force with the bottom portion outside is applied to allow the cells to penetrate into the biological tissue filling material. A container for manufacturing a biological tissue filling body for manufacturing a biological tissue filling body by the above, wherein the bottom side is detachable.

Thus, when the living tissue filling material and the cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. Moreover, since the bottom part is removable, the body tissue filling body can be easily taken out.

In the invention according to claim 7, the porous biological tissue filling material and the cells are introduced, and a centrifugal force with the bottom portion outside is applied to allow the cells to permeate the biological tissue filling material. A container for producing a biological tissue filling body for producing a biological tissue filling body, wherein the bottom portion has a complementary shape to the living tissue filling material.

As a result, when the living tissue filling material and the cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. Moreover, since the bottom part has a complementary shape to the biological tissue filling material,
It is possible to prevent cells from passing through the tissue filling material by centrifugal force.

According to the eighth aspect of the present invention, a porous biological tissue filling material and cells are introduced, and a centrifugal force with the bottom portion outside is applied to allow the cells to permeate the biological tissue filling material. A biological tissue filling body manufacturing container for producing a living tissue filling body by the method, wherein the cross-sectional shape of the inner surface of the installation portion for installing the living tissue filling material is the same as the cross-sectional shape of the living tissue filling material, The inner diameter of the inner surface of the part is larger than the outer diameter of the biological tissue filling material.

According to a ninth aspect of the present invention, a porous biological tissue filling material and cells are introduced, and a centrifugal force with the bottom portion outside is applied to allow the cells to permeate the biological tissue filling material. A container for producing a biological tissue filling body for producing a biological tissue filling body, wherein a receiving portion for restricting movement of the living tissue filling material to the bottom side is provided at a position separated from the bottom portion. It is characterized by that.

As a result, when the living tissue filling material and cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. Moreover, since the living tissue filling material is held at a position separated from the bottom by the receiving portion, when the living tissue filling material has pores capable of capturing cells, unnecessary components such as interstitial fluid pass through the living tissue filling material. By allowing the cells to reach the bottom side, only the cells can be allowed to remain in a state of permeating the inside of the tissue filling material.

According to a tenth aspect of the present invention, there is provided a syringe main body of a sampling syringe having a cylindrical syringe main body and a piston inserted into the syringe main body, and the syringe main body is detachably joined to the inside of the syringe main body. It has a lid capable of holding the biological tissue filling material and constituting the bottom portion when a centrifugal force is applied.

As a result, after the cells are extracted with the sampling syringe, the piston is removed, the lid body holding the biological tissue filling material inside is attached to the syringe body, and centrifugal force is applied with the lid body on the bottom side. Then, the cells are forcibly permeated into the biological tissue filling material by the centrifugal force. Moreover, since the syringe main body of the sampling syringe is shared, the number of devices used can be reduced.

The eleventh aspect of the invention is characterized by having a chamber in which the porous biological tissue filling material and cells are put together, and a centrifugal force applying means for applying a centrifugal force to the chamber.

Thus, when the living tissue filling material and the cells are introduced into the chamber and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force.

[0027]

BEST MODE FOR CARRYING OUT THE INVENTION A first embodiment of the present invention will be described below with reference to FIG. Here, as the bone filling material 11 as the living tissue filling material which is the base of the bone filling body 10 as the living tissue filling body manufactured in the first embodiment,
For example, a block-shaped porous body made of β-TCP (β-tricalcium phosphate) produced by the method disclosed in JP-A-5-237178 is used.

The manufacturing container 12 of the first embodiment has a substantially bottomed cylindrical shape, and has a substantially cylindrical main body 14 and is detachably attached to one end opening side of the main body 14 for manufacturing. The bottom side member 15 including the bottom 15A of the container 12 is included. Here, the main body portion 14 and the bottom portion side member 15 are detachable from each other by screwing.

The bottom member 15 has a semi-spherical surface 15a which is convex on the opposite side to the main body 14 inside, and the bottom 15A side of the main body 14 has a step portion having a larger diameter than the other portions. 16
Are formed. On the other hand, the bone filling material 11 is the bottom member 1
5, a hemispherical surface 1 having a complementary shape to the inner hemispherical surface 15a
1a.

Then, the bone filling material 11 is provided in the bottom member 15.
The bottom-side member 15 is joined to the main body portion 14 in the state of housing. Then, the bone prosthetic material 11 has its hemispherical surface 11a joined to the hemispherical surface 15a of the bottom member 15 and the step portion 1
At 6, the movement of the manufacturing container 12 is restricted. The manufacturing container 12 in which the bone filling material 11 is housed inside is prepared at the start of surgery.
At this time, the cross-sectional shape of the inner surface of the bottom side member 15 that is the installation portion of the bone prosthetic material 11 in the manufacturing container 12 in the direction orthogonal to the axis is the same as the cross-sectional shape of the bone prosthetic material 11 in the direction orthogonal to the axis. The inner diameter of the inner surface of the member 15 is made larger than the outer diameter of the bone filling material 11.

During the operation, the bone marrow fluid 17 is extracted from the patient's iliac bone, for example, and the bone marrow fluid 17 is used for the production container 12
Pour into the chamber inside. And this manufacturing container 12
As shown in FIG. 2, a centrifugal separator (centrifugal force imparting means) 102 having a rotating part 100 for obliquely installing a plurality of positions at positions equidistant from the rotation axis and a motor 101 for rotating the rotating part 100. It is installed on the rotating unit 100. When the rotating part 100 of the centrifuge 102 is rotated, a centrifugal force is applied to the manufacturing container 12 so that the bottom part 15A revolves around the center of rotation provided on the outer side thereof. Then, from the bone marrow fluid 17, desired cells (hereinafter simply referred to as desired cells) mainly composed of hematopoietic stem cells, mesenchymal stem cells and blood cells, which have a higher specific gravity than the tissue fluid, are transferred to the bottom 15A side by centrifugal force. It moves and is forcibly permeated into the inside of the porous bone substitute material 11 provided on the bottom portion 15A.

Then, after the separated tissue fluid is discharged from the opening on the side opposite to the bottom portion 15A of the manufacturing container 12, the bottom portion side member 15 is removed from the main body portion 14,
The bone filling body 10 is taken out.

As described above, the bone filling body 10 in which desired cells of the bone marrow fluid 17 are applied to the bone filling material 11 is obtained, and the bone filling body 10 is filled in a bone defect portion (not shown). .

According to the first embodiment described above, the desired cells are forcibly permeated into the bone prosthetic material 11 by the centrifugal force, so that even within the limited time, the bone prosthetic material 11 can be reached. It is possible to obtain the bone prosthesis 10 to which desired cells are sufficiently added, and as a result, it is possible to increase the speed of repair of a bone defect portion after surgery. Moreover, the step portion 16 of the manufacturing container 12 prevents the bone filling material 11 from forming on the manufacturing container 12.
Since the movement of the bone filling material 11 is regulated, a desired cell can be surely permeated into the bone prosthetic material 11 by applying a centrifugal force. In addition, the bottom side member 15 of the manufacturing container 12
The bone filling material 11 can be easily attached to and detached from the manufacturing container 12 as a result of being attached to and detached from the main body portion 14, and as a result, the workability of loading and unloading operations can be improved. .

Here, by adjusting the speed of centrifugation by the centrifuge and the size of the pores of the bone filling material 11, desired cells can be more evenly permeated into the bone filling material 11.

As shown in FIG. 3, if complementary taper surfaces 11b and 15b are formed on the bone filling material 11 and the bottom portion 15A, the taper surfaces 11b and 15b of the bone filling material 11 at the time of centrifugal force application. Since the movement with respect to the bottom portion 15A can be restricted, the step portion 16 can be eliminated from the manufacturing container 12.

It is also possible to use, as the bone filling material 11, a granular material instead of a block material. By making it granular like this, the surface area can be increased,
The desired cells can be efficiently permeated, and the contact between the stem cells in the desired cells on each surface can be increased. At this time, in particular, the manufacturing container 12
In the above, it is preferable to mix the granular bone filling material so that the bone filling material has substantially the same density as the desired cells. With this configuration, the bone prosthetic material and the desired cells can be mixed evenly by the centrifugal force, and the desired cells can be more efficiently permeated into the bone prosthetic material. further,
The clot (coagulated mass) may be produced by mixing desired cells and the granular bone prosthetic material 11 and then mixing with the platelet concentrate.

Further, as shown in FIG. 4, the manufacturing container 12
If the receiving portion 18 that restricts the movement of the bone prosthesis material 11 to the bottom portion 15A side is formed at a position spaced from the bottom portion 15A of the, the position separated from the bottom portion 15A by the receiving portion 18 even when centrifugal force is applied. The bone filling material 11 can be held by By doing this, when the bone filling material 11 has pores capable of capturing desired cells, unnecessary components such as tissue fluid in the bone marrow fluid 17 are passed through the bone filling material 11 and eliminated to the bottom portion 15A side. It is possible to allow only the cells to remain in a state of permeating the inside of the bone prosthetic material 11. At this time, in addition to forming the receiving portion 18 by bending the manufacturing container 12 itself as shown in FIG. 4, a cylindrical shape is formed on the inner peripheral surface of the manufacturing container 12 having a straight shape as shown in FIG. The receiving portion 18 is formed by joining the receiving members 19 in the shape of a circle.
May be formed.

Further, as shown in FIG. 6, a bottomed cylindrical manufacturing container 12 may be used, and a bone prosthesis material 11 and a bone marrow fluid 17 are put in a chamber inside the manufacturing container 12 and not shown. As shown in FIG. 7, the lid is put on the rotating portion 105 of a centrifugal separator (centrifugal force applying means) 107 having a rotating portion 105 and a motor 106 for rotating the rotating portion 105.
When the rotating part 105 of the centrifugal separator 107 is rotated,
The manufacturing container 12 is rotated about its central axis. As a result, desired cells having a higher specific gravity than the tissue fluid are extracted from the bone marrow fluid 17 by the centrifugal force to the inner wall 1 of the container 12 for production.
It is possible to forcibly permeate the inside of the porous bone prosthetic material 11 which is moved to the side of 2a and is also moved to the side of the inner wall 12a of the manufacturing container 12 by centrifugal force. Note that, as shown in FIG. 6, a plurality of bone prosthesis materials 11 may be arranged in advance along the inner wall 12a before centrifugation.

Next, the second embodiment of the present invention will be described below mainly with reference to FIGS. 8 and 9 focusing on the differences from the first embodiment. The same parts as those in the first embodiment are designated by the same reference numerals, and the description thereof will be omitted.

The manufacturing container of the second embodiment is a syringe main body of a collection syringe 26 having a cylindrical syringe main body 24 having an injection needle 23 shown in FIG. 8 and a piston 25 inserted into the syringe main body 24. As shown in FIG. 9, the syringe body 24 has a syringe body 24 and a lid body 27 detachably joined to the opposite side of the injection needle 23 of the syringe body 24, that is, the opening side. . The syringe body 24 and the lid 27 are detachably joined to each other by screwing. In addition, the syringe body 2
4 is a main part 24A detachably joined by screw connection
And a tip portion 24B to which the injection needle 23 is attached.

The lid 27 has the same β-type as in the first embodiment.
For example, a mesh-shaped holding member 28 capable of holding a cylindrical bone prosthetic material 11 made of a porous body of TCP and allowing desired cells to pass therethrough is provided inside. In addition, before starting the surgery, the bone filling material 11 is attached to the lid 27 in advance.
Are held by the holding member 28.

Then, during the operation, after the bone marrow fluid 17 is extracted from the patient by the sampling syringe 26, the piston 25 is removed from the sampling syringe 26 while the injection needle 23 is on the lower side, and the injection needle 23 of the syringe body 24 is removed. On the opposite side, the holding member 2
The lid 27 in which the bone filling material 11 is held inside by 8
Attach. Then, turn it upside down to remove the syringe body 24.
From the injection needle 23 or, if necessary, the tip portion 24B together with the tip portion 24B to remove the manufacturing container 12, and the manufacturing container 12 is set in the centrifuge with the lid 27 at the bottom side, and the center of rotation provided on the outside thereof is set. Centrifugal force is applied so that the bottom part revolves outward with the center as the center. Then, among the bone marrow fluid 17, desired cells mainly composed of hematopoietic stem cells, mesenchymal stem cells, and blood cells, which have a higher specific gravity than the tissue fluid, move to the bottom side by centrifugal force and move to the bottom side of the porous cells. Bone filling material 1
As a result of being forcibly permeated into the inside of No. 1, the same effect as the first embodiment is obtained. Moreover, since the syringe body 24 of the sampling syringe 26 is shared with the manufacturing container 12, the number of devices used can be reduced.

Also in the second embodiment, it is also possible to use, as the bone filling material 11, a granular material instead of a block material. Since the surface area can be increased by forming the granules in this manner, desired cells can be efficiently permeated into the bone prosthetic material, and the contact of stem cells with each other on the bone prosthetic material surface can be increased. At this time, the first
As in the embodiment, it is preferable to mix the granular bone filling material in the production container 12 so that the bone filling material has substantially the same density as the desired cells.

Here, in the first and second embodiments, the case where the bone marrow fluid 17 extracted from the patient during the operation is directly injected into the manufacturing container 12 has been described as an example. By injecting only cells consisting mainly of hematopoietic stem cells and mesenchymal stem cells and blood cells in which tissue fluid and the like have been removed by centrifuging the bone marrow fluid in advance, or extracted by further filtering or centrifugation, It is also possible to inject only the mesenchymal stem cells, which are the most important for increasing the repair speed of the postoperative bone defect. In addition to bone marrow fluid, peripheral blood or body fluid such as cord blood that has been stored in advance may be used. The means for obtaining the desired cells may be an immunomagnetic cell separation device or flow cytometry. In addition, erythrocytes in blood are bound to unnecessary cells through an antibody complex to form a rosette, and unnecessary cells that have become rosettes are removed by centrifugation. The desired cells to be concentrated may not be precipitated, but desired cells may be recovered from the upper layer of the medium for specific gravity separation, and may be further injected into the container 12 to give a centrifugal force together with the biological tissue filling material.

In addition, in the case of injecting any desired cells such as bone marrow fluid and mesenchymal stem cells into the manufacturing container 12 in the first and second embodiments, cytokine, concentrated platelets, BMP, FGF are obtained. , IGF, TGF-β, VEG
If necessary, a substance that contributes to growth such as F, PDGF, and HGF may be added, and by doing so, the rate of repair of the bone defect portion after surgery can be further increased. here,
The platelet concentrate is applied after the cells have penetrated into the bone prosthetic material 11.

Next, the third embodiment of the present invention will be mainly described with reference to FIG.
The following description will be centered on the difference from the first embodiment with reference to FIG. The same parts as those in the first embodiment are designated by the same reference numerals, and the description thereof will be omitted.

In the third embodiment, the bone filling material 11
However, the main body 3 is formed of a porous body of β-TCP similar to that of the first embodiment, but is formed in a cylindrical shape, specifically, a bottomed cylindrical shape.
0 and a lid 31 fitted into the opening 30a of the main body 30.

Then, as in the first embodiment, the bone marrow fluid 17 extracted from the patient during the operation is injected into the inside of the main body 30, the opening 30a of the main body 30 is closed with the lid 31, and the centrifuge is used. Then, the bone prosthetic material 11 is rotated about the central axis of the bone prosthetic material 11 to apply centrifugal force. Then, from bone marrow fluid 17, desired cells mainly composed of hematopoietic stem cells, mesenchymal stem cells, and blood cells, which have a higher specific gravity than the tissue fluid, are centrifugally applied to the bone prosthetic material 1
The first main body 30 moves to the inner wall 30b side and is forcibly permeated inside, and the same effect as the first embodiment is achieved.

Moreover, since the bone substitute material 11 is formed in a container shape and the bone marrow fluid 17 is directly injected, the container is not required. Of course, this bone filling material 11 may be put in a container.

In the third embodiment, a granular bone filling material (not shown) is introduced into the main body 30 of the tubular bone filling material 11 together with the bone marrow fluid 17, the lid 31 is fitted, and centrifugal force is applied. May be added. With this configuration, the space inside the tubular bone filling material 11 can be reduced by the granular bone filling material.

In the third embodiment, the case where the bone marrow fluid 17 extracted from the patient during the operation is directly injected into the container-shaped bone prosthesis 11 has been described as an example. Unnecessary components including tissue fluid have been removed by centrifuging the liquid, and only desired cells consisting of hematopoietic stem cells, mesenchymal stem cells, and blood cells are injected, or extracted by filtering or centrifugation. It is also possible to inject only mesenchymal stem cells, which are the most important for increasing the speed of repair of bone defects after surgery.

Further, in the third embodiment, even when bone marrow fluid or desired cells such as mesenchymal stem cells are injected into the container-shaped bone filling material 11, growth of cytokines, concentrated platelets and the like occurs. If necessary, a substance that contributes to the bone defect may be added. By doing so, the rate of repair of the bone defect portion after surgery can be further increased. Here, the concentrated platelets are applied after the cells have penetrated into the bone prosthetic material 11 by centrifugal force.

In addition, in the first to third embodiments, if the bone filling material is a porous biocompatible material, β-
In addition to TCP, HAP (hydroxyapatite)
PLA (polylactic acid), PGA (polyglycolic acid), PLGA (polylactic acid polyglycolic acid copolymer)
It is possible to use those made of other various materials such as. In addition, the living tissue that is the filling destination is cartilage other than bone,
It may be epidermis, dermis, nerve, cornea, muscle or the like. Further, the target or desired cells to be the source of centrifugation may be cells contained in bone marrow fluid, mesenchymal stem cells, or differentiated osteocytes, osteoblasts, or osteoclasts in addition to bone marrow fluid. good. The mesenchymal stem cells may be stem cells collected from peripheral blood or cord blood. Furthermore, ES cells may be used. Substances that contribute to growth are BMP, FGF, TGF-β, IGF, PD
It may be GF, VEGF, HGF or a combination thereof.

[0055]

As described above in detail, according to the invention of claim 1, when the living tissue filling material and the cells are introduced into the manufacturing container and a centrifugal force is applied, the living tissue filling material is centrifugally applied. The cells are forced to penetrate inside. Therefore, it is possible to obtain a body tissue filling body in which cells are sufficiently added to the inside of the body tissue filling material even within a limited time, and as a result, the repair speed of the body tissue defect portion after surgery can be increased. You can

According to the second aspect of the present invention, since the living tissue filling material is in the form of granules, the surface area is increased, cells can be efficiently permeated into the living tissue filling material, and the living tissue filling material surface It is possible to increase contact between cells in.

According to the third aspect of the present invention, since the granular living tissue filling material is blended so as to have substantially the same density as the cells, the living tissue filling material and the cells are evenly mixed by centrifugal force. The cells can be combined with each other, and the cells can be more efficiently permeated into the biological tissue filling material.

According to the fourth aspect of the present invention, when cells are introduced into the tubular tissue filling material and a centrifugal force is applied to the tissue filling material, the cells are placed inside the tissue filling material by the centrifugal force. Is forced to penetrate. Therefore, even within a limited time, it is possible to obtain a body tissue filling body in which cells are sufficiently provided to the inside of the body tissue filling material,
As a result, it is possible to increase the speed of repair of the biological tissue defect portion after surgery. Moreover, since the living tissue filling material is formed in a container shape and cells are directly injected, the container is not required.

According to the fifth aspect of the invention, when the cells and the granular living tissue filling material are introduced inside the tubular living tissue filling material to impart a centrifugal force to the living tissue filling material, the centrifugal force is applied. Thus, the cells are forcibly permeated into the tubular tissue filling material, and the cells are forcibly permeated into the granular tissue filling material by centrifugal force. Moreover, since the granular living tissue filling material is put into the tubular living tissue filling material, the space inside the tubular living tissue filling material can be reduced.

According to the sixth aspect of the present invention, when the living tissue filling material and the cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. . Therefore, it is possible to obtain a body tissue filling body in which cells are sufficiently added to the inside of the body tissue filling material even within a limited time, and as a result, the repair speed of the body tissue defect portion after surgery can be increased. You can Moreover, since the bottom part is removable, the body tissue filling body can be easily taken out. Therefore, the workability of the take-out work is improved.

According to the invention of claim 7, when the living tissue filling material and the cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. . Moreover, since the bottom portion has a complementary shape to the living tissue filling material, it is possible to prevent cells from passing through the living tissue filling material by centrifugal force. Therefore, even within a limited time, it is possible to obtain a body tissue filling body in which cells are sufficiently provided to the inside of the body tissue filling material,
As a result, it is possible to increase the speed of repair of the biological tissue defect portion after surgery.

According to the invention of claim 9, when the living tissue filling material and the cells are introduced and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. . Moreover, since the living tissue filling material is held at a position separated from the bottom by the receiving portion, when the living tissue filling material has pores capable of capturing cells, unnecessary components such as interstitial fluid pass through the living tissue filling material. By allowing the cells to reach the bottom side, only the cells can be allowed to remain in a state of permeating the inside of the tissue filling material. Therefore, it becomes possible to efficiently obtain a living tissue filling material in which cells have been sufficiently added to the inside of the living tissue filling material even within a limited time, and as a result, the repair speed of the living tissue defective portion after surgery can be improved. Can be increased.

According to the tenth aspect of the invention, after the cells are extracted with the sampling syringe, the piston is removed, the lid body holding the biological tissue filling material inside is attached to the syringe body, and the lid body is attached to the bottom portion. When the centrifugal force is applied to the side, the cells are forcibly permeated into the biological tissue filling material by the centrifugal force. Therefore, it is possible to obtain a body tissue filling body in which cells are sufficiently added to the inside of the body tissue filling material even within a limited time, and as a result, the repair speed of the body tissue defect portion after surgery can be increased. You can Moreover, since the syringe main body of the sampling syringe is shared, the number of devices used can be reduced.

According to the eleventh aspect of the invention, when the living tissue filling material and the cells are introduced into the chamber and a centrifugal force is applied, the cells are forcibly permeated into the living tissue filling material by the centrifugal force. . Therefore, it is possible to obtain a body tissue filling body in which cells are sufficiently added to the inside of the body tissue filling material even within a limited time, and as a result, the repair speed of the body tissue defect portion after surgery can be increased. You can

[Brief description of drawings]

FIG. 1 is a front cross-sectional view showing a container for manufacturing a biological tissue filling body according to a first embodiment of the present invention.

FIG. 2 is a front cross-sectional view showing a container and a centrifuge for producing a biological tissue filling body according to the first embodiment of the present invention.

FIG. 3 is a front cross-sectional view showing a modified example 1 of the container for manufacturing a biological tissue filling body according to the first embodiment of the present invention.

FIG. 4 is a front cross-sectional view showing a modified example 2 of the container for manufacturing a biological tissue filling body according to the first embodiment of the present invention.

FIG. 5 is a front cross-sectional view showing a modified example 3 of the container for manufacturing a biological tissue filling body according to the first embodiment of the present invention.

FIG. 6 is a plan sectional view showing a modified example 4 of the container for manufacturing a biological tissue filling body according to the first embodiment of the present invention.

FIG. 7 is a side sectional view showing a modified example 4 of the container for producing a biological tissue filler according to the first embodiment of the present invention and a centrifuge.

FIG. 8 is a front cross-sectional view showing a container for production of a biological tissue filler according to a second embodiment of the present invention and a sampling syringe partially used.

FIG. 9 is a cross-sectional view showing a container for manufacturing a biological tissue filling body according to a second embodiment of the present invention.

FIG. 10 is a perspective view showing a container for manufacturing a biological tissue filling body according to a third embodiment of the present invention.

[Explanation of symbols]

10 Bone filling material (living tissue filling material) 11 Bone filling material (living tissue filling material) 12 Manufacturing container 15A bottom 17 bone marrow fluid 18 Receiver 24 Syringe body 25 pistons 26 Syringe 27 Lid 28 Holder

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Hiroki Hibino             2-43 Hatagaya, Shibuya-ku, Tokyo Ori             Inside Npus Optical Industry Co., Ltd. (72) Inventor Ryoji Saito             2-43 Hatagaya, Shibuya-ku, Tokyo Ori             Inside Npus Optical Industry Co., Ltd. (72) Inventor Hideki Koyanagi             2-43 Hatagaya, Shibuya-ku, Tokyo Ori             Inside Npus Optical Industry Co., Ltd. F-term (reference) 4C081 AB04 BA12 DA03 DA11 DB03                       EA06                 4C097 AA01 BB01 CC01 DD07 DD15                       EE08 FF01 MM03 MM04 MM08

Claims (11)

[Claims] 1. A method for producing a biological tissue filling body, which comprises forming a living tissue filling body to be filled in a living tissue defective portion by permeating cells into a porous living tissue filling material, the method comprising: A method for producing a biological tissue filling body, which comprises introducing the biological tissue filling material and the cells and applying centrifugal force thereto. 2. The method for producing a body tissue filling body according to claim 1, wherein a granular material is used as the body tissue filling material. 3. The method for producing a biological tissue filling material according to claim 2, wherein the granular biological tissue filling material is blended so as to have substantially the same density as the cells. 4. A method for producing a living tissue filling body, which comprises forming a living tissue filling body to be filled in a living tissue defective portion by infiltrating cells into a porous living tissue filling material, the living tissue filling body comprising: A method for producing a biological tissue filling body, which comprises forming a material into a tubular shape and introducing the cells into the tubular biological tissue filling material to apply a centrifugal force to the biological tissue filling material. 5. The method for introducing a centrifugal force to the tubular biological tissue filling material by introducing a granular biological tissue filling material into the tubular biological tissue filling material together with the cells inside the tubular biological tissue filling material. Item 5. A method for producing a biological tissue filling body according to item 4. 6. A biological tissue filling material is introduced by introducing a porous living tissue filling material and cells and applying a centrifugal force with the bottom portion to the outside so that the living tissue filling material is permeated with the cells. A container for manufacturing a biological tissue filling body to be manufactured, wherein the bottom side is detachable. 7. A biological tissue filling material is introduced by introducing a porous living tissue filling material and cells and applying a centrifugal force with the bottom portion to the outside so that the living tissue filling material is permeated with the cells. A container for producing a biological tissue filling body to be produced, wherein the bottom portion has a complementary shape to the biological tissue filling material. 8. A biological tissue filling material is introduced by introducing a porous living tissue filling material and cells and applying a centrifugal force with the bottom portion to the outside so that the living tissue filling material is permeated with the cells. A container for producing a biological tissue filling body to be produced, wherein the cross-sectional shape of the installation portion inner surface for installing the biological tissue filling material is the same as the cross-sectional shape of the living tissue filling material, and the inner diameter of the installation portion inner surface is A container for producing a biological tissue filling body, wherein the container has a larger outer diameter than the biological tissue filling material. 9. A porous tissue filling material and cells are introduced, and a centrifugal force is applied with the bottom portion outside so that the cells penetrate into the living tissue filling material to form a living tissue filling body. A container for producing a living tissue filling body to be manufactured, wherein a receiving portion for restricting movement of the living tissue filling material to the bottom portion side is provided at a position separated from the bottom portion. Tissue filling container for manufacturing. 10. A biological tissue filling material is introduced by introducing a porous living tissue filling material and cells and applying a centrifugal force with the bottom portion to the outside so that the living tissue filling material is permeated with the cells. A container for producing a biological tissue filler to be produced, the syringe body of a collection syringe having a cylindrical syringe body and a piston inserted into the syringe body,
For manufacturing a biological tissue filling body, which is detachably joined to the syringe body and has a lid capable of holding the biological tissue filling material inside and forming the bottom portion when centrifugal force is applied. container. 11. An apparatus for producing a biological tissue filling body, comprising: a chamber into which a porous biological tissue filling material and cells are put together; and a centrifugal force applying means for applying a centrifugal force to the chamber.