JP2004049626A - Filling material of osteochondral defect and filling body of osteochondral defect and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To repair defect of cartilage tissues without cutting of healthy cartilage tissues. <P>SOLUTION: A composite film 2 composed of calcium phosphate and a biodegradable material softer than the calcium phosphate is joined to a porous material 3 composed of the calcium phosphate to form a filling material of an osteochondral defect 1. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an osteochondral prosthesis, an osteochondral prosthesis, and a method for producing the same.
[0002]
[Prior art]
For articular cartilage damage that cannot be repaired spontaneously, a method of transplanting articular cartilage tissue of a non-weighted part of a patient and a method of transplanting cultured chondrocytes in a suspension state have been used. Since the cartilage tissue transplantation is a method of cutting out a healthy non-loaded articular cartilage tissue and replenishing the defective part, there is a disadvantage that a new defect is generated.
For transplantation in the form of a suspension of cultured cartilage, a very small amount of cartilage tissue is collected from the non-loading part cartilage tissue of a patient and cultured and propagated in vitro. However, in this method, it has been pointed out that there is a problem that the transplanted cells leak or that the cultured chondrocytes in the monolayer culture cannot sufficiently function as hyaline chondrocytes.
[0003]
Therefore, an approach using a tissue engineering technique combining a chondrocyte and a living tissue has been developed. As a biomaterial, a sponge made of a bioabsorbable polymer material such as polylactic acid, polyglycolic acid, and collagen is used, and cartilage tissue has been successfully regenerated as a scaffold for chondrocytes.
[0004]
[Problems to be solved by the invention]
However, in these conventional techniques, the degree of articular cartilage damage progresses because only chondrocytes are cultured, and application becomes difficult when a large cartilage defect occurs. That is, there is a problem that the adhesion between the subchondral bone and the transplanted cartilage tissue is detached, and the function of the transplanted cartilage tissue cannot be sufficiently exhibited. On the other hand, if the method is to cut out the cartilage tissue of the non-loading part together with the subchondral bone and transplant it to the defect part, the function as the cartilage tissue is secured, but not only the cartilage defect but also the bone defect in the non-loading part There is an inconvenience of causing. In addition, if the transplantation is performed in a small amount, the cartilage tissue and the bone tissue at the sampling site are repaired over time, but it is difficult to repair the transplantation defect with the amount of the transplantation site normally required.
[0005]
The present invention has been made in view of the above circumstances, and has an osteochondral filling material and an osteochondral filling material capable of repairing a defect in cartilage tissue without removing healthy cartilage tissue, and production thereof. It is intended to provide a way.
[0006]
[Means for Solving the Problems]
In order to achieve the above object, the present invention provides the following means.
The invention according to claim 1 provides an osteochondral filling material formed by joining a composite membrane made of calcium phosphate and a biodegradable material softer than the same and a porous body made of calcium phosphate.
According to the present invention, bone tissue is cultured by culturing osteoblast-like cells in a porous body made of calcium phosphate, and culturing chondroblast-like cells in a composite membrane made of calcium phosphate and a softer biodegradable material. An osteochondral prosthesis can be manufactured in which a bone prosthesis for forming cartilage and a cartilage prosthesis for forming cartilage tissue are integrally joined.
[0007]
According to a second aspect of the present invention, there is provided the osteochondral replacement material according to the first aspect, wherein the porous body is impregnated with an antibiotic.
ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to suppress reproduction | regeneration of various bacteria, and to promote healthy osteochondral regeneration by the effect of an antibiotic.
[0008]
The invention according to claim 3 is a composite membrane comprising calcium phosphate and a biodegradable material softer than calcium phosphate, a composite membrane in which chondroblast-like cells are cultured, and a porous body comprising calcium phosphate, in which osteoblast-like cells are cultured. To provide an osteochondral prosthesis, which is joined with
According to the present invention, by filling the osteochondral prosthesis into the defect part generated in the cartilage tissue in the joint, the porous body in which the osteoblast-like cells are cultured can be used as the bone tissue in the portion where the joint is formed. Can be supported. Therefore, the cartilage tissue is regenerated while the composite membrane on which the chondroblast-like cells are cultured is supported by the bone tissue, and the defective portion of the cartilage tissue in the joint is repaired.
[0009]
The invention according to claim 4 is obtained by joining a composite membrane composed of calcium phosphate and a biodegradable material softer than that to a porous body composed of calcium phosphate, and mesenchymal stem cells are formed on the composite membrane and the porous substance. An applied osteochondral prosthesis is provided. According to the present invention, in a composite membrane, mesenchymal stem cells are differentiated into chondroblasts, and in a porous body, mesenchymal stem cells are differentiated into osteoblasts, thereby repairing cartilage tissue defects in joints. It becomes possible.
[0010]
The invention according to claim 5 is characterized in that chondroblast-like cells are cultured in a composite membrane comprising calcium phosphate and a softer biodegradable material, and osteoblast-like cells are cultured in a porous body composed of calcium phosphate. Provided is a method for producing an osteochondral prosthesis, which is cultured for a predetermined period in a state where a composite membrane in which blast-like cells are cultured and a porous body in which osteoblast-like cells are cultured.
According to the present invention, the chondroblast-like cells cultured on the composite membrane and the osteoblast-like cells cultured on the porous body are cultured again for a predetermined period of time. Bud-like cells grow to penetrate each other. Therefore, an osteochondral prosthesis having an increased binding strength is produced by growing the cells in an intertwined manner and being connected to each other.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
An osteochondral filler and an osteochondral filler according to an embodiment of the present invention and a method for producing the same will be described below with reference to the drawings.
As shown in FIG. 1, the osteochondral filler 1 according to the present embodiment includes a bioabsorbable polymer material such as L-type polylactic acid (hereinafter, referred to as PLLA) and β-tricalcium phosphate (hereinafter, β). -TCP), and a composite film 2 made of calcium phosphate, represented by, for example, and a porous body 3 made of calcium phosphate.
[0012]
The porous body 3 made of calcium phosphate (for example, described as a β-TCP porous body) is manufactured by slurrying, foaming, drying, and sintering β-TCP powder. Further, the composite membrane 2 composed of PLLA and β-TCP is manufactured by mixing a bioabsorbable polymer material with a calcium phosphate slurry, followed by foaming and drying.
[0013]
The concentration of β-TCP can be adjusted as needed. (Because it is desirable that the amount of β-TCP is as small as possible as a culture carrier for chondrocytes, it is also possible to add and mix β-TCP powder in a molten state of PLLA, if necessary.)
Bonding of the composite membrane 2 of PLLA and β-TCP to the β-TCP porous body 3 can be performed using a biological adhesive such as fibrin glue. May be welded. The osteochondral prosthesis thus produced may be impregnated with an antibiotic. As the antibiotic, for example, a penicillin antibiotic can be used.
[0014]
The thus configured osteochondral prosthesis 1 according to the present embodiment is effective as a scaffold for a prosthesis for joint tissue.
That is, since the composite membrane 2 is composed of β-TCP and PLLA which is softer than that, if the chondrocytes are cultured here, the cartilage tissue to be regenerated is appropriately soft and has high strength. It can be manufactured. On the other hand, since the porous body 3 is composed of β-TCP, if bone cells are cultured here, it is possible to produce a bone tissue that is harder than cartilage tissue and has sufficiently high strength. .
[0015]
Next, the osteochondral prosthesis 10 according to the present embodiment will be described below. The osteochondral prosthesis 10 according to the present embodiment is manufactured as follows.
As shown in FIG. 2, first, the above-mentioned composite membrane 2 and porous body 3 are separately prepared (steps 1 and 2), and chondroblast-like cells are used in composite membrane 2 and osteoblast-like cells are used in porous body 3. Cells are seeded and cultured separately (steps 3 and 4). The culture is performed, for example, in a suitable medium at 37 ° C. and a 5% CO ₂ concentration for a predetermined period. Chondroblast-like cells and osteoblast-like cells were produced, for example, by primary culture of bone marrow fluid collected from a patient to obtain mesenchymal stem cells, and by causing each of the differentiation-inducing factors to act thereon. Things.
[0016]
The composite membrane 2 carrying the cultured chondroblast-like cells and the porous body 3 carrying the cultured osteoblast-like cells thus formed are bonded to each other by, for example, fibrin glue ( Step 5). Then, in this state, culturing is performed in a further appropriate medium for a predetermined period (step 6).
Thereby, while the chondroblast-like cells cultured on the composite membrane 2 grow on the porous body 3 side, the osteoblast-like cells cultured on the porous body 3 grow on the composite membrane 2 side and are entangled with each other and high. It will be joined with strength. By using this function, a bonding agent such as fibrin glue can be eliminated in step 5.
[0017]
Then, in order to apply the thus configured osteochondral prosthesis 10 to a joint defect, as shown in FIG. 3, first, (a) a defect 5 generated in the cartilage tissue 4 of the joint is removed. (B) The bone tissue 6 joined to the cartilage tissue 4 corresponding to the defect 5 is excised. Next, (c) the osteochondral prosthesis 10 produced as described above is supplemented. The portion of the porous body 3 of β-TCP in which the osteoblast-like cells are cultured in the osteochondral prosthesis 1 is fitted into the concave portion 7 formed in the bone tissue 6 constituting the joint, while the chondroblast-like cells are cultured. The obtained composite membrane 2 is placed so as to be in contact with the healthy cartilage tissue 4 after the removal of the defect 5.
[0018]
As a result, regeneration of the bone tissue is induced in the portion of the porous body 3 where the osteoblast-like cells are cultured by using the porous body 3 as a scaffold, while regeneration of the cartilage tissue is induced in the composite membrane 2 in which the chondrocytes are cultured. Then, with time, the porous body 3 is replaced with autologous bone, and the composite membrane 2 is decomposed and replaced with cartilage. As a result, the defect 5 generated in the cartilage tissue 4 is repaired.
Further, according to the osteochondral prosthesis 10 according to the present embodiment, since the porous body 3 is impregnated with the antibiotic, even during the culturing or after the defective part 5 is supplemented, the action of this antibiotic allows Infection of bacteria and the like is prevented, and healthy cell growth is promoted.
[0019]
As described above, according to the osteochondral prosthesis 1 and the osteochondral prosthesis 10 and the method of manufacturing the osteochondral prosthesis according to the present embodiment, the osteochondral having the bone prosthesis and the cartilage prosthesis artificially joined with a high joining force is provided. Since the prosthesis 10 is provided, it is possible to repair the defective portion 5 in the cartilage tissue 4 without removing the healthy cartilage tissue 4 as in the case of mosaic plasticity. Therefore, the burden on the patient can be reduced by eliminating a major operation. In addition, since the healthy cartilage tissue 4 is not substituted, the healthy cartilage tissue 4 is not lost.
[0020]
In addition, according to the osteochondral prosthesis 10 according to the present embodiment, a predetermined culture period is required until the osteochondral prosthesis 10 is manufactured. Therefore, when urgency is required, the healthy cartilage tissue 4 is temporarily substituted by mosaic plasticity. It is also possible to do. In such a case, the cartilage tissue 4 is regenerated at the resected portion by replenishing the portion from which the healthy cartilage tissue 4 has been resected by mosaic plasticity with the osteochondral prosthesis 10 according to the present embodiment. Can be.
[0021]
In the present embodiment, PLLA is used as a biodegradable material softer than β-TCP, but polylactic acid, polyglycolic acid, collagen, or hyaluronic acid may be used instead.
As calcium phosphate, β-tricalcium phosphate having absorbability is most preferable, but other calcium phosphate having biocompatibility such as apatite may be used instead.
In addition, although penicillin antibiotics are employed as antibiotics, any antibiotics such as cephem, macrolide, tetracycline, fosfomycin, aminoglycoside, and new quinolone can be employed instead.
[0022]
【The invention's effect】
As described above, according to the osteochondral prosthesis, the osteochondral prosthesis, and the method of manufacturing the same according to the present invention, it is possible to firmly fix the defect in the cartilage tissue of the joint and repair the defect. it can. Moreover, since there is no need to remove healthy cartilage tissue, there is also an effect that the burden on the patient can be reduced.
[Brief description of the drawings]
FIG. 1 is a longitudinal sectional view showing an osteochondral substitute according to an embodiment of the present invention.
FIG. 2 is a flowchart showing a method of manufacturing an osteochondral prosthesis according to one embodiment of the present invention.
FIG. 3 is a diagram illustrating a procedure for filling the osteochondral prosthesis of FIG. 2 into a defective portion of cartilage tissue.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Osteochondral substitute 2 Composite membrane 3 Porous body 10 Osteochondral substitute

Claims (5)

An osteochondral filling material formed by joining a composite membrane made of calcium phosphate and a biodegradable material softer than that to a porous body made of calcium phosphate. The osteochondral filling material according to claim 1, wherein the porous body is impregnated with an antibiotic. Osteochondral replenishment consisting of a composite membrane made of calcium phosphate and a softer biodegradable material and cultured with chondroblast-like cells and a porous body made of calcium phosphate and cultured with osteoblast-like cells body. An osteochondral prosthesis in which a composite membrane made of calcium phosphate and a softer biodegradable material is bonded to a porous body made of calcium phosphate, and the composite membrane and the porous body are provided with mesenchymal stem cells. . Culturing chondroblast-like cells in a composite membrane consisting of calcium phosphate and a softer biodegradable material,
Osteoblast-like cells are cultured on a porous body made of calcium phosphate,
A method for producing an osteochondral prosthesis, wherein the composite membrane in which the chondroblast-like cells are cultured and the porous body in which the osteoblast-like cells are cultured are joined and cultured for a predetermined period.

Images