JP2011078710A - Implantation material for cartilage - Google Patents

Implantation material for cartilage Download PDF

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JP2011078710A
JP2011078710A JP2009236264A JP2009236264A JP2011078710A JP 2011078710 A JP2011078710 A JP 2011078710A JP 2009236264 A JP2009236264 A JP 2009236264A JP 2009236264 A JP2009236264 A JP 2009236264A JP 2011078710 A JP2011078710 A JP 2011078710A
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cartilage
biodegradable polymer
layer
porous
porous film
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JP5545563B2 (en
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Rie Tsuchiya
利江 土屋
Shigeyuki Wakitani
滋之 脇谷
Takashi Shigematsu
貴 重松
Ayako Iwata
綾子 岩田
Koji Hakamazuka
康治 袴塚
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Olympus Corp
Olympus Terumo Biomaterials Corp
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Olympus Terumo Biomaterials Corp
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an implantation material for cartilage which simply restores a defective part of the cartilage. <P>SOLUTION: The implantation material 1 for the cartilage includes a block-shaped porous body 5 composed of biodegradable polymer porous material and a porous film 4 composed of a biodegradable polymer porous material covering a part of the surface, and in the implantation material 1 for the cartilage, the air hole diameter of the porous film 4 has a size to prohibit passing of a cartilage cell and a mesenchymal stem cell and to allow passing of a bodily liquid. Thus, the defective part C of the cartilage is easily restored without sampling/cultivating the cartilage cell. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

本発明は、軟骨用移植材に関するものである。   The present invention relates to a cartilage transplant.

従来、軟骨組織の修復を目的として、軟骨組織から得られる軟骨細胞を特定の担体にて培養し、移植材を形成する方法が知られている（例えば、特許文献１参照。）。   Conventionally, for the purpose of repairing cartilage tissue, a method is known in which chondrocytes obtained from cartilage tissue are cultured on a specific carrier to form a transplant (see, for example, Patent Document 1).

特開２００２−２３３５６７号公報JP 2002-233567 A

しかし、軟骨細胞の採取は正常な軟骨組織への侵襲を伴い、また細胞の分離や担体を用いた培養には特定の技術や時間を要するという不都合がある。
本発明は、軟骨細胞の採取・培養を行うことなく、簡易に軟骨の欠損部を修復することができる軟骨用移植材を提供することを目的としている。 However, the collection of chondrocytes involves the invasion of normal cartilage tissue, and there is a disadvantage that a specific technique and time are required for cell separation and culture using a carrier.
An object of the present invention is to provide a cartilage transplant material that can easily repair a cartilage defect without collecting and culturing chondrocytes.

上記目的を達成するために、本発明は以下の手段を提供する。
本発明は、生分解性高分子多孔質材料からなるブロック状の多孔質体と、その一表面を被覆する生分解性高分子多孔質材料からなる多孔質フィルムとを備え、該多孔質フィルムの気孔径が、軟骨細胞および間葉系幹細胞の通過を禁止し、体液を通過可能な大きさを有する軟骨用移植材を提供する。 In order to achieve the above object, the present invention provides the following means.
The present invention comprises a block-like porous body made of a biodegradable polymer porous material and a porous film made of a biodegradable polymer porous material covering one surface of the porous film. Provided is a cartilage transplant having a pore size that inhibits the passage of chondrocytes and mesenchymal stem cells and has a size that allows passage of bodily fluids.

本発明によれば、軟骨用移植材を、軟骨下骨の表面に配される軟骨層または軟骨下骨まで到達するように形成された欠損部に移植する場合に、多孔質フィルムが軟骨層の表面側に配されるように移植することにより、多孔質体が欠損部内に挿入され、多孔質体の一面を被覆している多孔質フィルムが欠損部に蓋をするように配置される。多孔質体内には軟骨層に存在している軟骨細胞や骨髄液に含まれる骨髄由来の間葉系幹細胞が侵入し、軟骨組織が形成される。この際に、多孔質体内に侵入した軟骨細胞や骨髄由来間葉系幹細胞は多孔質体の一面を被覆する多孔質フィルムによって軟骨層の表面側に漏出することが阻止され、多孔質体内に留まって軟骨組織の再生が促進される。さらに、多孔質フィルムの気孔を介して体液が多孔質体側に流入し、簡易に軟骨の欠損部を修復することができる。   According to the present invention, when a graft material for cartilage is transplanted into a cartilage layer disposed on the surface of the subchondral bone or a defect formed so as to reach the subchondral bone, the porous film is formed of the cartilage layer. By transplanting so as to be arranged on the surface side, the porous body is inserted into the defect portion, and the porous film covering one surface of the porous body is arranged so as to cover the defect portion. Chondrocytes existing in the cartilage layer and bone marrow-derived mesenchymal stem cells contained in the bone marrow fluid enter the porous body, and cartilage tissue is formed. At this time, chondrocytes and bone marrow-derived mesenchymal stem cells that have entered the porous body are prevented from leaking to the surface side of the cartilage layer by the porous film covering one surface of the porous body, and remain in the porous body. Thus, regeneration of cartilage tissue is promoted. Furthermore, the body fluid flows into the porous body through the pores of the porous film, and the cartilage defect can be easily repaired.

上記発明においては、前記多孔質フィルムの気孔径が、５μｍ未満、好ましくは１μｍ未満、より好ましくは０．５μｍ未満であることが好ましい。このようにすることで、多孔質体内に侵入した軟骨細胞や間葉系幹細胞の漏出をより確実に防止することができるとともに、多孔質フィルムを介した体液の多孔質体内への侵入を許容して、軟骨組織の再生を促進することができる。   In the said invention, it is preferable that the pore diameter of the said porous film is less than 5 micrometers, Preferably it is less than 1 micrometer, More preferably, it is less than 0.5 micrometer. In this way, it is possible to more reliably prevent the leakage of chondrocytes and mesenchymal stem cells that have entered the porous body, and to allow intrusion of body fluid into the porous body through the porous film. Thus, regeneration of cartilage tissue can be promoted.

また、上記発明においては、前記多孔質体が、前記多孔質フィルムにより被覆された表面とは反対の表面側に、リン酸カルシウム顆粒が混合されたリン酸カルシウム含有層を備えることとしてもよい。
このようにすることで、軟骨用移植材を、軟骨下骨の表面に配される軟骨層に軟骨下骨まで到達するように形成された欠損部に移植する場合に、リン酸カルシウム含有層を軟骨下骨側に向けて移植することにより、リン酸カルシウム含有層において軟骨下骨の再生促進を図ることができる。 Moreover, in the said invention, the said porous body is good also as providing the calcium-phosphate content layer by which the calcium-phosphate granule was mixed in the surface side opposite to the surface coat | covered with the said porous film.
In this way, when the graft material for cartilage is transplanted to a defect portion formed so as to reach the subchondral bone to the cartilage layer arranged on the surface of the subchondral bone, the calcium phosphate-containing layer is placed under the cartilage By transplanting toward the bone side, regeneration of subchondral bone can be promoted in the calcium phosphate-containing layer.

また、上記発明においては、前記多孔質体を構成する生分解性高分子多孔質材料が、アテロコラーゲンを再線維化させた再線維化コラーゲンと、アテロコラーゲンを熱変性させた熱変性コラーゲンとを混合し架橋させたものであることが好ましい。
このようにすることで、抗原性のあるテロペプチドが除かれた材料を使用して、軟骨細胞や間葉系幹細胞の侵入性を向上し、軟骨組織の再生をさらに容易にすることができる。 In the above invention, the biodegradable polymer porous material constituting the porous body is a mixture of refibrinated collagen obtained by refibrating atelocollagen and heat-denatured collagen obtained by heat-denaturing atelocollagen. It is preferable that it is what was bridge | crosslinked.
In this way, by using the material from which the antigenic telopeptide is removed, the invasion property of chondrocytes and mesenchymal stem cells can be improved, and the regeneration of the cartilage tissue can be further facilitated.

また、本発明は、生分解性高分子多孔質材料からなる生分解性高分子層と、該生分解性高分子層の一面側に配置され、リン酸カルシウム顆粒を含有する生分解性高分子多孔質材料からなるリン酸カルシウム含有層と、前記生分解性高分子層の他面側に配置され、該生分解性高分子層より気孔率の小さい生分解性高分子多孔質材料からなる多孔質フィルムとを積層してなる軟骨用移植材を提供する。   The present invention also relates to a biodegradable polymer layer comprising a biodegradable polymer porous material and a biodegradable polymer porous material disposed on one side of the biodegradable polymer layer and containing calcium phosphate granules. A calcium phosphate-containing layer made of a material, and a porous film made of a biodegradable polymer porous material disposed on the other side of the biodegradable polymer layer and having a lower porosity than the biodegradable polymer layer. Provided is a cartilage graft material that is laminated.

本発明によれば、軟骨用移植材を、軟骨下骨の表面に配される軟骨層または軟骨下骨まで到達するように形成された欠損部に移植する場合に、多孔質フィルムが軟骨層の表面側に配されるように移植することにより、多孔質体が欠損部内に挿入され、多孔質体の一面を被覆している多孔質フィルムが欠損部に蓋をするように配置される。多孔質体内には軟骨層に存在している軟骨細胞や骨髄液に含まれる骨髄由来の間葉系幹細胞が侵入し、軟骨組織が形成される。この際に、多孔質体内に侵入した軟骨細胞や骨髄由来間葉系幹細胞は多孔質体の一面を被覆する多孔質フィルムによって軟骨層の表面側に漏出することが抑制され、多孔質体内に留まって軟骨組織の再生が促進される。さらに、多孔質フィルムの気孔を介して体液が多孔質体側に流入し、簡易に軟骨の欠損部を修復することができる。   According to the present invention, when a graft material for cartilage is transplanted into a cartilage layer disposed on the surface of the subchondral bone or a defect formed so as to reach the subchondral bone, the porous film is formed of the cartilage layer. By transplanting so as to be arranged on the surface side, the porous body is inserted into the defect portion, and the porous film covering one surface of the porous body is arranged so as to cover the defect portion. Chondrocytes existing in the cartilage layer and bone marrow-derived mesenchymal stem cells contained in the bone marrow fluid enter the porous body, and cartilage tissue is formed. At this time, chondrocytes and bone marrow-derived mesenchymal stem cells that have entered the porous body are prevented from leaking to the surface side of the cartilage layer by the porous film covering one surface of the porous body, and remain in the porous body. Thus, regeneration of cartilage tissue is promoted. Furthermore, the body fluid flows into the porous body through the pores of the porous film, and the cartilage defect can be easily repaired.

また、上記発明においては、前記生分解性高分子層および前記リン酸カルシウム含有層を構成する生分解性高分子多孔質材料が、アテロコラーゲンを再線維化させた再線維化コラーゲンと、アテロコラーゲンを熱変性させた熱変性コラーゲンとを混合し架橋させたものであってもよい。
このようにすることで、抗原性のあるテロペプチドが除かれた材料を使用して、軟骨細胞や間葉系幹細胞の侵入性を向上し、軟骨組織の再生をさらに容易にすることができる。 Further, in the above invention, the biodegradable polymer porous material constituting the biodegradable polymer layer and the calcium phosphate-containing layer comprises refibrinated collagen obtained by refibrating atelocollagen and heat-denatured atelocollagen. It is also possible to mix and crosslink with heat-denatured collagen.
In this way, by using the material from which the antigenic telopeptide is removed, the invasion property of chondrocytes and mesenchymal stem cells can be improved, and the regeneration of the cartilage tissue can be further facilitated.

本発明によれば、軟骨細胞の採取・培養を行うことなく、簡易に軟骨の欠損部を修復することができるという効果を奏する。   According to the present invention, it is possible to easily repair a cartilage defect without collecting and culturing chondrocytes.

本発明の一実施形態に係る軟骨用移植材を示す模式的な縦断面図である。It is a typical longitudinal section showing the transplant material for cartilage concerning one embodiment of the present invention. 図１の軟骨用移植材を欠損部に移植する場合を説明する図であり、（ａ）欠損部への軟骨用移植材の挿入、（ｂ）欠損部に移植された状態の軟骨用移植材をそれぞれ示す縦断面図である。It is a figure explaining the case where the transplant material for cartilage of FIG. 1 is transplanted to a defect part, (a) Insertion of the transplant material for cartilage to a defect part, (b) The transplant material for cartilage of the state transplanted to the defect part FIG. 図２（ｂ）により欠損部に移植された軟骨用移植材に作用する軟骨細胞、骨髄液および体液をそれぞれ示す縦断面図である。It is a longitudinal cross-sectional view which each shows the chondrocyte, bone marrow fluid, and bodily fluid which act on the transplant material for cartilage transplanted by the defect part by FIG.2 (b). 図１の軟骨用移植材の変形例を示す縦断面図である。It is a longitudinal cross-sectional view which shows the modification of the transplant material for cartilage of FIG. 図４の軟骨用移植材を欠損部に移植する場合を説明する図であり、（ａ）欠損部への軟骨用移植材の挿入、（ｂ）欠損部に移植された状態の軟骨用移植材をそれぞれ示す縦断面図である。It is a figure explaining the case where the transplant material for cartilage of FIG. 4 is transplanted to a defect part, (a) Insertion of the transplant material for cartilage to a defect part, (b) The transplant material for cartilage of the state transplanted to the defect part FIG.

本発明の一実施形態に係る軟骨用移植材１について、図面を参照して以下に説明する。
本実施形態に係る軟骨用移植材１は、図１に示されるように、生分解性高分子多孔質材料からなる第１の層２と、該第１の層２の一面に配置され同じく生分解性高分子多孔質材料にリン酸カルシウム顆粒を含有してなる第２の層（リン酸カルシウム含有層）３と、第１の層２の他面を被覆するように配置された生分解性高分子多孔質材料からなる多孔質フィルム４とを備えた３層構造を有している。 A cartilage implant 1 according to an embodiment of the present invention will be described below with reference to the drawings.
As shown in FIG. 1, a cartilage implant 1 according to the present embodiment is disposed on a first layer 2 made of a biodegradable polymer porous material and on one surface of the first layer 2 and Biodegradable polymer porous material disposed so as to cover a second layer (calcium phosphate-containing layer) 3 containing calcium phosphate granules in a degradable polymer porous material and the other surface of the first layer 2 It has a three-layer structure including a porous film 4 made of a material.

第１の層２および第２の層３を構成する生分解性高分子多孔質材料は、例えば、以下のようにして製造される。
まず、コラーゲンからテロペプチドを除去したアテロコラーゲンの塩酸溶液を２つ用意し、一方のアテロコラーゲン塩酸溶液は中和した後に３７℃で４．５時間程度静置することにより、再線維化コラーゲン溶液を生成し、この再線維化コラーゲン溶液を濃縮および洗浄することにより、再線維化コラーゲンを得る。他方のアテロコラーゲン塩酸溶液は、凍結乾燥後に溶解したものを６０℃で３０分程度静置することにより熱変性コラーゲンを得て、ここに緩衝溶液を添加することにより中和する。得られた再線維化コラーゲンと熱変性コラーゲンとを混合したものに、架橋剤を混合することにより、材料となる生分解性高分子多孔質材料を得る。架橋剤としては、エポキシ基を両末端に備える化合物、例えば、デナコール（登録商標：ナガセケムテックス株式会社製）である。 The biodegradable polymer porous material constituting the first layer 2 and the second layer 3 is produced, for example, as follows.
First, prepare two atelocollagen hydrochloric acid solutions from which telopeptide has been removed from collagen, and neutralize one atelocollagen hydrochloric acid solution, and leave it at 37 ° C for about 4.5 hours to produce a refibrotic collagen solution. Then, the refibrinated collagen solution is obtained by concentrating and washing the refibrinated collagen solution. The other atelocollagen hydrochloric acid solution is freeze-dried and left at 60 ° C. for about 30 minutes to obtain heat-denatured collagen, and neutralized by adding a buffer solution thereto. A biodegradable polymer porous material to be a material is obtained by mixing a cross-linking agent with the obtained mixture of refibrinated collagen and heat-denatured collagen. The crosslinking agent is a compound having an epoxy group at both ends, for example, Denacol (registered trademark: manufactured by Nagase ChemteX Corporation).

生分解性高分子材料とリン酸カルシウム顆粒とを混合し、任意の容器内に流入させることにより第２の層３を得る。その後、第２の層３の上層に材料である生分解性高分子多孔質材料を流入させることにより、第２の層３の一面側に積層状態に形成された第１の層２を得る。そして、これを凍結乾燥することにより２層構造のブロック状の多孔質体５を得ることができる。   The second layer 3 is obtained by mixing the biodegradable polymer material and the calcium phosphate granules and allowing them to flow into an arbitrary container. Thereafter, a biodegradable polymer porous material, which is a material, is allowed to flow into the upper layer of the second layer 3 to obtain the first layer 2 formed in a laminated state on one surface side of the second layer 3. And the block-shaped porous body 5 of 2 layer structure can be obtained by freeze-drying this.

一方、多孔質フィルム４は以下のようにして製造する。
容器に、ゼラチン、グリセロールおよび架橋剤の混合溶液を収容し、３７℃で乾燥させることによりフィルム状に構成する。
このようにして構成された多孔質フィルム４は、１μｍ以下の気孔径を有している。したがって、５〜５０μｍ程度の大きさを有する軟骨細胞や骨髄由来間葉系幹細胞は多孔質フィルム４の気孔を通過することができない。一方、体液については多孔質フィルム４の気孔を通過することができる。 On the other hand, the porous film 4 is manufactured as follows.
The container contains a mixed solution of gelatin, glycerol and a crosslinking agent, and is formed into a film by drying at 37 ° C.
The porous film 4 thus configured has a pore diameter of 1 μm or less. Therefore, chondrocytes and bone marrow-derived mesenchymal stem cells having a size of about 5 to 50 μm cannot pass through the pores of the porous film 4. On the other hand, the body fluid can pass through the pores of the porous film 4.

このようにして構成された多孔質フィルム４は、例えば、一面に架橋剤を混合したゼラチン溶液を塗布し、その表面に、上記により構成された２層構造の多孔質体５の第１の層２の表面を密着させることにより、両者を接着する。これにより、多孔質フィルム４、第１の層２および第２の層３の３層構造からなる軟骨用移植材１を得ることができる。また、得られた軟骨用移植材を大量の温水で洗浄することにより、余分な架橋剤を除去することができる。   For example, the porous film 4 thus configured is coated with a gelatin solution mixed with a crosslinking agent on one surface, and the first layer of the porous body 5 having the two-layer structure configured as described above is applied to the surface thereof. The two surfaces are adhered to each other by bringing them into close contact with each other. As a result, the cartilage implant 1 having a three-layer structure of the porous film 4, the first layer 2 and the second layer 3 can be obtained. Further, the excess cross-linking agent can be removed by washing the obtained cartilage transplant with a large amount of warm water.

次に、このようにして構成された本実施形態に係る軟骨用移植材１の作用について説明する。
本実施形態に係る軟骨用移植材１は、図２に示されるように、軟骨層Ａから軟骨下骨Ｂまで達する欠損部Ｃに移植するためのものである。 Next, the operation of the cartilage transplant material 1 according to this embodiment configured as described above will be described.
The cartilage transplant 1 according to the present embodiment is for transplantation into a defect C reaching from the cartilage layer A to the subchondral bone B as shown in FIG.

図２（ａ）に示されるように、第２の層３が、欠損部Ｃの底部Ｃ１に向かうようにして、欠損部Ｃ内に軟骨用移植材１を挿入する。これにより、図２（ｂ）に示されるように、第２の層３が欠損部Ｃの軟骨下骨Ｂ部分に挿入され、第１の層２が、欠損部Ｃの軟骨層Ａ部分に配置される。 As shown in FIG. 2A, the cartilage implant 1 is inserted into the defect C such that the second layer 3 faces the bottom C 1 of the defect C. Thereby, as shown in FIG. 2B, the second layer 3 is inserted into the subchondral bone B portion of the defect portion C, and the first layer 2 is disposed in the cartilage layer A portion of the defect portion C. Is done.

欠損部Ｃ内の軟骨層Ａ部分においては、図３に示されるように、軟骨層Ａから染み出した軟骨細胞Ｄが第１の層２内に浸透する。また、軟骨下骨Ｂから染み出してきた骨髄液Ｆが第２の層３を通り第１の層２内に浸透する。第１の層２の表面には多孔質フィルム４によって覆われているので、該多孔質フィルム４が蓋として機能し、第１の層２内に浸透した軟骨細胞Ｄおよび骨髄液Ｆに含有されている間葉系幹細胞は多孔質フィルム４を通過することができずに第１の層２内に留められる。一方、多孔質フィルム４には体液Ｅを通過させることができる大きさの気孔が設けられているので、多孔質フィルム４を貫通して体液Ｅが第１の層２内に浸透する。   In the cartilage layer A portion in the defect C, the chondrocytes D that have exuded from the cartilage layer A penetrate into the first layer 2 as shown in FIG. Further, the bone marrow fluid F that has exuded from the subchondral bone B passes through the second layer 3 and penetrates into the first layer 2. Since the surface of the first layer 2 is covered with the porous film 4, the porous film 4 functions as a lid and is contained in the chondrocytes D and bone marrow fluid F that have penetrated into the first layer 2. Mesenchymal stem cells that are present cannot pass through the porous film 4 and remain in the first layer 2. On the other hand, since the porous film 4 is provided with pores having a size that allows the body fluid E to pass therethrough, the body fluid E penetrates into the first layer 2 through the porous film 4.

軟骨細胞Ｄおよび骨髄液Ｆが第１の層２内に浸透することで、第１の層２内においては軟骨組織の再生が行われ、多孔質フィルム４によって第１の層２からの軟骨細胞Ｄおよび骨髄液Ｆに含有されている間葉系幹細胞の漏出が防止されることで、第１の層２内に留められた軟骨細胞Ｄおよび間葉系幹細胞による軟骨組織の再生が維持される。さらに、多孔質フィルム４を介して第１の層２内に浸透した体液Ｅ内に含有されている成長因子、また骨髄液Ｆ内に含有されている成長因子等の作用によって軟骨組織の再生が促進される。   As the chondrocytes D and bone marrow fluid F penetrate into the first layer 2, the cartilage tissue is regenerated in the first layer 2, and the chondrocytes from the first layer 2 are formed by the porous film 4. By preventing leakage of mesenchymal stem cells contained in D and bone marrow fluid F, regeneration of cartilage tissue by chondrocytes D and mesenchymal stem cells retained in the first layer 2 is maintained. . Furthermore, the regeneration of the cartilage tissue is caused by the action of the growth factor contained in the body fluid E that has penetrated into the first layer 2 through the porous film 4 and the growth factor contained in the bone marrow fluid F. Promoted.

また、欠損部Ｃ内の軟骨下骨Ｂ部分においては、図３に示されるように、軟骨下骨Ｂから染み出してきた骨髄液Ｆが第２の層３内に浸透する。第２の層３内にはリン酸カルシウム顆粒が含有されているので、骨髄液Ｆ内に含有されている間葉系幹細胞がリン酸カルシウム顆粒を足場として成長し、軟骨下骨Ｂ組織が再生される。これにより、軟骨下骨Ｂまで達する欠損部Ｃを簡易に修復することができる。   Further, in the subchondral bone B portion in the defect C, the bone marrow fluid F that has exuded from the subchondral bone B penetrates into the second layer 3 as shown in FIG. Since the calcium phosphate granules are contained in the second layer 3, the mesenchymal stem cells contained in the bone marrow fluid F grow using the calcium phosphate granules as a scaffold, and the subchondral bone B tissue is regenerated. Thereby, the defect portion C reaching the subchondral bone B can be easily repaired.

なお、本実施形態においては、３層構造からなる軟骨用移植材１を例示したが、これに代えて、図４に示されるように、生分解性高分子多孔質材料からなるブロック状の多孔質体５の一面に、上述した多孔質フィルム４が貼り付けられた２層構造の軟骨用移植材１を採用してもよい。   In the present embodiment, the cartilage transplant material 1 having a three-layer structure is illustrated, but instead of this, as shown in FIG. 4, a block-shaped porous material made of a biodegradable polymer porous material is used. The cartilage transplant material 1 having a two-layer structure in which the porous film 4 described above is attached to one surface of the mass 5 may be employed.

このような２層構造の軟骨用移植材１は、軟骨下骨まで到達するように形成された欠損部にも適用可能であるが、図５（ａ）に示されるように、軟骨層Ａのみに欠損部Ｃが形成されているような場合に好適である。上記軟骨用移植材１と同様に、図５（ｂ）に示されるように、軟骨層Ａから染み出してきた軟骨細胞Ｄが多孔質体５内に取り込まれるとともに、多孔質フィルム４によってその漏出が防止される。そして、多孔質フィルム４を介して多孔質体５内へ浸透してきた体液Ｅによって、軟骨組織の再生が促進される。   The cartilage graft material 1 having such a two-layer structure can be applied to a defect formed so as to reach the subchondral bone, but only the cartilage layer A is shown in FIG. 5 (a). This is suitable for the case where the defect portion C is formed on the surface. Similar to the cartilage graft material 1, as shown in FIG. 5 (b), the chondrocytes D oozing out from the cartilage layer A are taken into the porous body 5 and leaked out by the porous film 4. Is prevented. Then, regeneration of the cartilage tissue is promoted by the body fluid E that has permeated into the porous body 5 through the porous film 4.

また、本実施形態においては、再線維化コラーゲンと熱変性コラーゲンとを混合した生分解性高分子多孔質材料により多孔質体５を製造することとしたが、これに代えて、純水で膨潤させたゼラチンを５０℃で溶解し、架橋剤を投入してミキサーにて攪拌し発泡させたものを用いて多孔質体５を製造することにしてもよい。
また、第１の層２と第２の層３を同一の生分解性高分子多孔質材料により製造することとしたが、これに代えて、異なる材料により構成してもよい。さらに、架橋剤により架橋させることで多孔質体５を構成することとしたが、これに代えて、架橋剤を加えることなく熱架橋により多孔質体５を製造することにしてもよい。 In the present embodiment, the porous body 5 is manufactured from a biodegradable polymer porous material in which refibrinated collagen and heat-denatured collagen are mixed. Instead, the porous body 5 is swollen with pure water. The porous body 5 may be manufactured using a solution obtained by dissolving the gelatin at 50 ° C., adding a crosslinking agent, stirring the mixture with a mixer and foaming.
Although the first layer 2 and the second layer 3 are made of the same biodegradable polymer porous material, they may be made of different materials instead. Further, the porous body 5 is configured by crosslinking with a crosslinking agent. Alternatively, the porous body 5 may be manufactured by thermal crosslinking without adding a crosslinking agent.

Ａ 軟骨層
Ｂ 軟骨下骨
Ｃ 欠損部
Ｃ１ 底部
Ｄ 軟骨細胞
Ｅ 体液
Ｆ 骨髄液
１ 軟骨用移植材
２ 第１の層（生分解性高分子層）
３ 第２の層（リン酸カルシウム含有層）
４ 多孔質フィルム
５ 多孔質体 A Cartilage layer B Subchondral bone C Deficient part C 1 Bottom part D Chondrocytes E Body fluid F Bone marrow fluid 1 Cartilage graft material 2 First layer (biodegradable polymer layer)
3 Second layer (calcium phosphate-containing layer)
4 Porous film 5 Porous body

Claims (6)

生分解性高分子多孔質材料からなるブロック状の多孔質体と、その一表面を被覆する生分解性高分子多孔質材料からなる多孔質フィルムとを備え、
該多孔質フィルムの気孔径が、軟骨細胞および間葉系幹細胞の通過を禁止し、体液を通過可能な大きさを有する軟骨用移植材。 A block-like porous body made of a biodegradable polymer porous material, and a porous film made of a biodegradable polymer porous material covering one surface thereof,
A graft material for cartilage, wherein the pore size of the porous film prohibits the passage of chondrocytes and mesenchymal stem cells, and has a size that allows passage of bodily fluids. 前記多孔質フィルムの気孔径が、１μｍ未満である請求項１に記載の軟骨用移植材。   The transplant material for cartilage according to claim 1, wherein a pore diameter of the porous film is less than 1 μm. 前記多孔質体が、前記多孔質フィルムにより被覆された表面とは反対の表面側に、リン酸カルシウム顆粒が混合されたリン酸カルシウム含有層を備える請求項１または請求項２に記載の軟骨用移植材。   The transplant material for cartilage according to claim 1 or 2, wherein the porous body includes a calcium phosphate-containing layer in which calcium phosphate granules are mixed on the surface opposite to the surface covered with the porous film. 前記多孔質体を構成する生分解性高分子多孔質材料が、アテロコラーゲンを再線維化させた再線維化コラーゲンと、アテロコラーゲンを熱変性させた熱変性コラーゲンとを混合し架橋させたものである請求項１に記載の軟骨用移植材。   The biodegradable polymer porous material constituting the porous body is obtained by mixing and cross-linking refibrinated collagen obtained by refibrating atelocollagen and heat-denatured collagen obtained by heat-denaturing atelocollagen. Item 2. The cartilage transplant material according to Item 1. 生分解性高分子多孔質材料からなる生分解性高分子層と、
該生分解性高分子層の一面側に配置され、リン酸カルシウム顆粒を含有する生分解性高分子多孔質材料からなるリン酸カルシウム含有層と、
前記生分解性高分子層の他面側に配置され、該生分解性高分子層より気孔率の小さい生分解性高分子多孔質材料からなる多孔質フィルムとを積層してなる軟骨用移植材。 A biodegradable polymer layer made of a biodegradable polymer porous material;
A calcium phosphate-containing layer that is disposed on one side of the biodegradable polymer layer and is made of a biodegradable polymer porous material containing calcium phosphate granules;
A graft material for cartilage, which is disposed on the other surface side of the biodegradable polymer layer and laminated with a porous film made of a biodegradable polymer porous material having a lower porosity than the biodegradable polymer layer. . 前記生分解性高分子層および前記リン酸カルシウム含有層を構成する生分解性高分子多孔質材料が、アテロコラーゲンを再線維化させた再線維化コラーゲンと、アテロコラーゲンを熱変性させた熱変性コラーゲンとを混合し架橋させたものである請求項５に記載の軟骨用移植材。   The biodegradable polymer porous material constituting the biodegradable polymer layer and the calcium phosphate-containing layer is a mixture of refibrinated collagen obtained by refibrating atelocollagen and heat-denatured collagen obtained by heat-denaturing atelocollagen. The cartilage transplant material according to claim 5, which is then cross-linked.
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