JP2005124709A - Biomaterial and its manufacturing method thereof - Google Patents

Biomaterial and its manufacturing method thereof Download PDF

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JP2005124709A
JP2005124709A JP2003361783A JP2003361783A JP2005124709A JP 2005124709 A JP2005124709 A JP 2005124709A JP 2003361783 A JP2003361783 A JP 2003361783A JP 2003361783 A JP2003361783 A JP 2003361783A JP 2005124709 A JP2005124709 A JP 2005124709A
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bone
strength
hole
filling material
calcium phosphate
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Koji Hakamazuka
康治 袴塚
Katsuya Sadamori
克也 貞森
Masahiro Kurosaka
昌弘 黒坂
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Olympus Corp
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Olympus Corp
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<P>PROBLEM TO BE SOLVED: To provide a biomaterial and a manufacturing method thereof capable of improving cell adhesion, ensuring a necessary strength for a region to be transplanted, and relieving strain on a patient. <P>SOLUTION: This bone replacement material (biomaterial) 1 is a scaffold material composed of porous calcium phosphate (for example, β-TCP) material, which includes a honeycomb-shaped main body 5 having a plurality of piercing holes 2 obtained by mutually partitioned by a partition 3 of about the same thickness. The piercing hole 2 is provided so as to be stuffed with a powder material (porous member) 6 containing calcium phosphate (for example, β-TCP). <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明は、生体組織補填材及びその製造方法に関する。   The present invention relates to a biological tissue filling material and a method for producing the same.

近年、骨腫瘍摘出や外傷等により生じた骨等の生体組織の欠損部に、骨補填材等の生体組織補填材を補填することにより、骨を再生させて欠損部を修復することが可能になってきている。骨補填材としては、ハイドロキシアパタイト（ＨＡＰ）やリン酸三カルシウム（ＴＣＰ）が知られているが、体内に異物を残さないとする考え方から、例えば、β−ＴＣＰのようなリン酸カルシウム多孔体からなる足場材が使用される。β−ＴＣＰを骨欠損部の骨細胞に接触させておくと、破骨細胞がβ−ＴＣＰを食べ、骨芽細胞が新しい骨を形成する、いわゆるリモデリングが行われる。すなわち、骨欠損部に補填された骨補填材は、経時的に自家骨に置換されていくことになる。   In recent years, it is possible to regenerate bone and repair the defect by repairing bone tissue or other biological tissue defect caused by bone tumor removal or trauma, etc. It has become to. Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are known as bone prosthetic materials, but from the idea that no foreign matter remains in the body, for example, it is made of a calcium phosphate porous material such as β-TCP. Scaffolding material is used. When β-TCP is kept in contact with bone cells in the bone defect portion, so-called remodeling is performed in which osteoclasts eat β-TCP and osteoblasts form new bone. That is, the bone prosthetic material supplemented in the bone defect portion is replaced with autologous bone over time.

一方、術後の骨欠損部の修復速度を高めるために、患者から採取した骨髄液に骨補填材を浸し、骨髄液に含まれる骨髄間葉系幹細胞を骨補填材とともに培養することにより製造される培養骨等の生体組織補填体を使用することが提案されている。培養されることにより骨補填材を足場にして増殖した多くの骨髄間葉系幹細胞を含む骨補填体を骨欠損部に補填するので、手術後に体内で細胞を増殖させる方法と比較すると、自家骨に置換されるまでの日数を大幅に短縮することができる（例えば、非特許文献１参照。）。
植村他２名，「生分解性β−ＴＣＰ多孔材料を用いた骨におけるティッシュエンジニアリング−生体内で強度を増す新しい材料オスフェリオン−」，メディカル朝日，朝日新聞社，２００１年１０月１日，第三０巻，第１０号，ｐ．４６−４９ On the other hand, it is manufactured by immersing a bone grafting material in bone marrow fluid collected from a patient and cultivating bone marrow mesenchymal stem cells contained in the bone marrow fluid together with the bone grafting material in order to increase the repair speed of the bone defect after surgery. It has been proposed to use a body tissue complement such as cultured bone. Since bone substitutes containing bone marrow mesenchymal stem cells that have been proliferated by using bone filler as a scaffold by culturing are filled in the bone defect, compared to the method of growing cells in the body after surgery, autologous bone The number of days until the replacement can be greatly reduced (see, for example, Non-Patent Document 1).
Uemura et al., “Tissue engineering in bone using biodegradable β-TCP porous material -Osferion, a new material that increases in vivo strength”, Medical Asahi, Asahi Shimbun, October 1, 2001, 3rd 0, No. 10, p. 46-49

しかしながら、骨補填材として多孔体を用いても骨髄間葉系幹細胞は骨補填材表面に留まるのみとなってしまい、骨補填材内部まで骨髄間葉系幹細胞を十分に付着させることが困難であった。また、骨補填材内部に上記細胞を付着させるために骨補填材の内部を貫通する貫通孔を形成させた場合、骨補填材の強度が低下してしまうため、患者に移植しても部位によっては強度不足となって十分な補填効果が得られない可能性があった。
本発明は上記事情に鑑みて成されたものであり、細胞の付着性を高めるとともに移植する部位に必要な強度を確保でき、患者の負担を軽減できる生体組織補填材及びその製造方法を提供することを目的とする。 However, even if a porous material is used as the bone grafting material, the bone marrow mesenchymal stem cells remain only on the surface of the bone grafting material, and it is difficult to sufficiently attach the bone marrow mesenchymal stem cells to the inside of the bone grafting material. It was. In addition, if a through-hole that penetrates the inside of the bone grafting material is formed in order to attach the cells to the inside of the bone grafting material, the strength of the bone grafting material is reduced. There was a possibility that sufficient strength could not be obtained due to insufficient strength.
The present invention has been made in view of the above circumstances, and provides a biological tissue filling material that can increase the adherence of cells, ensure the necessary strength for the site to be transplanted, and reduce the burden on the patient, and a method for producing the same. For the purpose.

本発明は、上記課題を解決するため、以下の手段を採用する。
本発明に係る生体組織補填材は、複数の貫通孔がリン酸カルシウムを含む隔壁によって相互に区画されたハニカム形状の本体を備え、少なくとも一つの前記貫通孔にリン酸カルシウムを含む多孔質部材が詰められていることを特徴とする。
この生体組織補填材は、表面積を大きく確保するために貫通孔を形成したことによって本体の強度が低下しても、貫通孔内の多孔質部材によって隔壁の変形を抑えてその強度を補なうことができ、多孔質部材がない貫通孔周辺よりも多孔質部材が詰められた貫通孔周辺の強度を高くすることができる。したがって、多孔質部材を詰める貫通孔の位置や数によって、一つの補填材内で補填すべき部位が必要とする強度に合わせて補填材の強度を調整することができる。 The present invention employs the following means in order to solve the above problems.
The biological tissue filling material according to the present invention includes a honeycomb-shaped main body in which a plurality of through holes are partitioned by partition walls containing calcium phosphate, and at least one of the through holes is packed with a porous member containing calcium phosphate. It is characterized by that.
Even if the strength of the main body is reduced due to the formation of the through hole in order to secure a large surface area, this biological tissue filling material compensates for the strength by suppressing the deformation of the partition wall by the porous member in the through hole. The strength around the through hole filled with the porous member can be made higher than that around the through hole without the porous member. Therefore, the strength of the filling material can be adjusted according to the strength required by the portion to be filled in one filling material, depending on the position and the number of through holes in which the porous member is filled.

また、本発明に係る生体組織補填材は、前記生体組織補填材であって、前記本体が生分解性高分子材料を含むことが好ましい。
この生体組織補填材は、生分解性高分子材料が弾性を有するので、本体に弾性を付加させることができる。したがって、変形させる力が負荷されても高分子材料を含まない場合よりも強度を高めることができる。 Moreover, the biological tissue filling material according to the present invention is the biological tissue filling material, and the main body preferably contains a biodegradable polymer material.
In this biological tissue filling material, the biodegradable polymer material has elasticity, so that elasticity can be added to the main body. Therefore, even when a force for deforming is applied, the strength can be increased as compared with the case where the polymer material is not included.

また、本発明に係る生体組織補填材は、前記生体組織補填材であって、少なくとも一部の前記隔壁の厚さが他の前記隔壁の厚さと異なっていることが好ましい。
この生体組織補填材は、強度の必要な部位には隔壁の壁厚を厚くし、強度が要らない部位では壁厚を薄くすることによって、一つの補填材内で強度の差異を備えることができ、補填すべき部位が必要とする強度に応じた構造とすることができる。 Moreover, the biological tissue filling material according to the present invention is the biological tissue filling material, wherein at least a part of the partition walls is preferably different in thickness from the other partition walls.
This biological tissue filling material can be provided with a difference in strength within a single filling material by increasing the wall thickness of the partition wall in areas where strength is required and decreasing the wall thickness in areas where strength is not required. The structure according to the strength required by the portion to be compensated can be obtained.

本発明に係る生体組織補填材の製造方法は、リン酸カルシウムを含む粉末にバインダを混入して原料を製造する工程と、前記原料から複数の貫通孔が隔壁によって相互に区画されたハニカム成形体を製造する工程と、前記ハニカム成形体を乾燥する工程と、前記貫通孔に多孔質部材を詰める工程と、前記ハニカム成形体を焼結する工程とを備えていることを特徴とする。   The method for manufacturing a tissue filling material according to the present invention includes a step of manufacturing a raw material by mixing a binder with powder containing calcium phosphate, and a honeycomb formed body in which a plurality of through holes are partitioned from each other by partition walls. A step of drying the honeycomb formed body, a step of filling the through hole with a porous member, and a step of sintering the honeycomb formed body.

この生体組織補填材の製造方法は、ハニカム成形体の貫通孔に多孔質部材を詰める工程を備えているので、多孔質部材がないものよりも貫通孔周辺の強度が高いものを製造することができる。この際、焼結前の隔壁に弾力性がまだある状態で多孔質部材を貫通孔に詰めるので、壁面を崩さずに押し込むことができる。また、焼結によって貫通孔が収縮するので多孔質部材を貫通孔内に閉じ込めることができる。
これによって、多孔質部材を詰める貫通孔の位置や数を変えて、一つの補填材内で補填すべき部位が必要とする強度に合わせて補填材の強度を調整することができる生体組織補填材を製造することができる。 Since this method for producing a tissue filling material includes a step of filling a porous member into the through hole of a honeycomb formed body, it is possible to manufacture a material having a higher strength around the through hole than that without a porous member. it can. At this time, since the porous member is packed in the through hole in a state where the partition wall before the sintering is still elastic, it can be pushed in without breaking the wall surface. Moreover, since the through hole contracts by sintering, the porous member can be confined in the through hole.
By this, the position and number of through-holes in which the porous member is packed can be changed to adjust the strength of the filling material according to the strength required by the site to be filled in one filling material. Can be manufactured.

本発明によれば、多孔性部材によって貫通孔近傍の強度を高めることができる。また、多孔性部材を詰める貫通孔を選択することによって、一つの補填材でも場所によって強度を変化させることができるので、手術時に必要な強度に合わせて補填材を選択する必要をなくすことができる。したがって、手技を確実に行うことができ、手技時間を短縮することができ、患者への負担を減らすことができる。   According to the present invention, the strength in the vicinity of the through hole can be increased by the porous member. In addition, by selecting the through-hole in which the porous member is packed, the strength can be changed depending on the location even with one filling material, so that it is not necessary to select the filling material according to the strength required at the time of surgery. . Therefore, the procedure can be performed reliably, the procedure time can be shortened, and the burden on the patient can be reduced.

本発明に係る第１の実施形態について、図１から図５を参照しながら説明する。
本実施形態に係る骨補填材（生体組織補填材）１は、図１に示すように、リン酸カルシウム（例えば、β−ＴＣＰ）多孔体からなる足場材であって、図２に示すように複数の貫通孔２が略同一厚さの隔壁３によって相互に区画されたハニカム形状の本体５を備え、貫通孔２にリン酸カルシウム（例えば、β−ＴＣＰ）を含む顆粒体（多孔質部材）６が詰められている。
本体５は、外形が円柱形状に形成されており、隔壁３によって貫通孔２が四角形状に区画されている。 A first embodiment according to the present invention will be described with reference to FIGS.
As shown in FIG. 1, a bone grafting material (biological tissue filling material) 1 according to the present embodiment is a scaffold made of a calcium phosphate (for example, β-TCP) porous body, and includes a plurality of scaffolding materials as shown in FIG. 2. The through-holes 2 are provided with honeycomb-shaped main bodies 5 that are partitioned by partition walls 3 having substantially the same thickness, and the through-holes 2 are packed with granules (porous members) 6 containing calcium phosphate (for example, β-TCP). ing.
The main body 5 has an outer shape formed in a cylindrical shape, and the through holes 2 are partitioned into quadrangular shapes by the partition walls 3.

次に、以上の構成からなる本実施形態に係る骨補填材１の製造方法について説明する。
骨補填材１は、図３に示すように、リン酸カルシウムを含む粉末にバインダを混入して原料を製造する工程（Ｓ０１）と、原料から複数の貫通孔２を備え本体５の基となるハニカム成形体を製造する工程（Ｓ０２）と、ハニカム成形体を乾燥する工程（Ｓ０３）と、貫通孔２に顆粒体６を詰める工程（Ｓ０４）と、ハニカム成形体を焼結する工程（Ｓ０５）とを備えている。
まず、原料の製造工程（Ｓ０１）にて、β−ＴＣＰを含む粉末にバインダ及び水を混ぜて混合発泡させた水性の発泡スラリを調整して数回混練してスラリ状に形成した原料を作製する。 Next, the manufacturing method of the bone grafting material 1 which concerns on this embodiment which consists of the above structure is demonstrated.
As shown in FIG. 3, the bone filling material 1 includes a step of manufacturing a raw material by mixing a binder with a powder containing calcium phosphate (S01), and a honeycomb molding that includes a plurality of through holes 2 from the raw material and serves as a base of a main body 5 A step of manufacturing the body (S02), a step of drying the honeycomb formed body (S03), a step of packing the granules 6 in the through holes 2 (S04), and a step of sintering the honeycomb formed body (S05). I have.
First, in the raw material manufacturing process (S01), an aqueous foamed slurry obtained by mixing and foaming a powder containing β-TCP with a binder and water is prepared and kneaded several times to produce a raw material formed into a slurry. To do.

続いて、ハニカム成形体を製造する工程（Ｓ０２）に移る。ここでは、例えば、特許第３４０５５３６号公報や特開平１０−５９７８４号公報に開示されている方法によって金型に原料を挿入して押出し成形してハニカム形状の成形体を成形する。
そして、脱バインダ処理としてハニカム成形体を乾燥する工程（Ｓ０３）に移り、ハニカム成形体を乾燥させる。 Then, it moves to the process (S02) which manufactures a honeycomb molded object. Here, for example, a raw material is inserted into a mold and extruded by a method disclosed in Japanese Patent No. 3405536 or Japanese Patent Laid-Open No. 10-59784 to form a honeycomb-shaped formed body.
And it moves to the process (S03) of drying a honeycomb molded object as a binder removal process, and dries a honeycomb molded object.

乾燥後、貫通孔２に顆粒体６を詰める工程（Ｓ０４）に移る。
ここでは、例えば、原料の製造工程（Ｓ０１）にて製造して粉末にする前のβ−ＴＣＰを含む複数の顆粒体６を貫通孔２に押し込む。
そして、ハニカム成形体を焼結する工程（Ｓ０５）では、焼結炉を用いて１０５０℃の温度で１時間、ハニカム成形体を加熱してβ−ＴＣＰを焼結する。この際、体積が全体的に２０〜３０％収縮する際に顆粒体６が貫通孔２内に閉じ込められる。
こうして得られた骨補填材１を補填する部位に適した大きさ・形状に最終的に加工する。 After drying, the process proceeds to the step of packing the granules 6 in the through holes 2 (S04).
Here, for example, a plurality of granules 6 including β-TCP before being made into a powder by being manufactured in the raw material manufacturing process (S01) are pushed into the through holes 2.
In the step of sintering the honeycomb formed body (S05), the honeycomb formed body is heated at a temperature of 1050 ° C. for 1 hour using a sintering furnace to sinter β-TCP. At this time, the granule 6 is confined in the through-hole 2 when the volume shrinks as a whole by 20 to 30%.
The bone prosthetic material 1 thus obtained is finally processed into a size and shape suitable for the site to be supplemented.

この骨補填材１によれば、骨補填材１の表面積を確保するために貫通孔２を内部に形成したことによって本体５の強度が低下しても、貫通孔２内の顆粒体６によって隔壁３を内側から外側へ加圧する力が生じているため、外力が負荷されてもこれに対抗して変形を抑えて強度を補なうことができ、顆粒体６が詰められた貫通孔２周辺の強度を高くすることができる。
この際、顆粒体６の密度を変えることによって内側からの加圧力を調整できる。したがって、貫通孔２全部でなく、図４及び図５に示すように、一つの補填材内で補填すべき部位が必要とする強度に合わせて選択した貫通孔２のみに顆粒体６を詰めることによって、場所によって補填材の強度に差異を設けて適当な強度に調整することができる。
また、顆粒体６もβ−ＴＣＰを備えて骨形成作用を有するので、顆粒体の数によって骨形成速度が異なることとなるため、顆粒体６の密度を変化させることで強度のみならず骨形成速度にも差異を持たせることができる。 According to this bone grafting material 1, even if the strength of the main body 5 is reduced due to the formation of the through hole 2 in order to ensure the surface area of the bone grafting material 1, the partition wall is formed by the granules 6 in the through hole 2. Since the force which presses 3 from the inside to the outside is generated, even if an external force is applied, the strength can be compensated by suppressing deformation against this, and the periphery of the through-hole 2 filled with the granules 6 The strength of can be increased.
At this time, the pressure from the inside can be adjusted by changing the density of the granules 6. Therefore, as shown in FIG. 4 and FIG. 5, the granules 6 are packed not only in the entire through-hole 2 but only in the through-hole 2 selected according to the strength required by the portion to be compensated in one filling material. Thus, the strength of the filling material can be varied depending on the location and adjusted to an appropriate strength.
In addition, since the granule 6 also has β-TCP and has an osteogenesis action, the bone formation speed varies depending on the number of granules. Therefore, by changing the density of the granule 6, not only the strength but also the bone formation. There can also be differences in speed.

次に、第２の実施形態について図６を参照しながら説明する。
なお、上述した第１の実施形態と同様の構成要素には同一符号を付すとともに説明を省略する。
第２の実施形態と第１の実施形態との異なる点は、第２の実施形態に係る骨補填材７の一部の隔壁８Ａの厚さが他の隔壁８Ｂの厚さと異なっているとした点である。 Next, a second embodiment will be described with reference to FIG.
In addition, the same code | symbol is attached | subjected to the component similar to 1st Embodiment mentioned above, and description is abbreviate | omitted.
The difference between the second embodiment and the first embodiment is that the thickness of some partition walls 8A of the bone grafting material 7 according to the second embodiment is different from the thickness of other partition walls 8B. Is a point.

本実施形態に係る骨補填材７の製造方法も上記第１の製造方法と同様であるが、ハニカム成形体を製造する工程（Ｓ０２）にて、隔壁厚が異なる金型を使用する。
この骨補填材７によれば、強度の必要な部位には一部の隔壁８Ａの壁厚を厚くし、強度が要らない部位では他の隔壁８Ｂの壁厚を薄くすることによって、一つの補填材内で強度に差異を備えることができ、補填すべき部位が必要とする強度に応じた構造とすることができる。 The manufacturing method of the bone grafting material 7 according to the present embodiment is the same as the first manufacturing method, but in the step (S02) of manufacturing the honeycomb formed body, dies having different partition wall thicknesses are used.
According to this bone grafting material 7, the wall thickness of some partition walls 8A is increased at a portion where strength is required, and the wall thickness of other partition walls 8B is decreased at a portion where strength is not required. A difference in strength can be provided in the material, and a structure corresponding to the strength required by the portion to be compensated can be obtained.

なお、本発明の技術範囲は上記実施の形態に限定されるものではなく、本発明の趣旨を逸脱しない範囲において種々の変更を加えることが可能である。
例えば、上記実施形態では、顆粒体６を貫通孔２に詰めるとしているが、貫通孔２に嵌合可能な多孔体を詰めてもよい。
また、貫通孔２の形状は四角形に限らず、図７に示すように、貫通孔１０が六角形の形状の骨補填材１１でもよく、図８に示すように、貫通孔１２が三角形の形状の骨補填材１３でも、他の多角形形状でも円形でも構わない。 The technical scope of the present invention is not limited to the above embodiment, and various modifications can be made without departing from the spirit of the present invention.
For example, in the above embodiment, the granules 6 are packed in the through holes 2, but a porous body that can be fitted into the through holes 2 may be packed.
Further, the shape of the through hole 2 is not limited to a quadrangle, and the through hole 10 may be a hexagonal bone filling material 11 as shown in FIG. 7, and the through hole 12 has a triangular shape as shown in FIG. The bone filling material 13 may be other polygonal shapes or circular shapes.

さらに、本体が生分解性高分子材料を含むものでも構わない。この場合、生分解性高分子材料が弾性を有するので、本体に弾性を付加させることができる。したがって、外部から本体を変形させる力が負荷されても弾性変形することによって緩和でき、高分子材料を含まない場合よりも強度を高めることができる。
この生分解性高分子材料としては、ゼラチン、ヒアルロン酸、フィブリン、アルギン酸、キチン−キトサン等の天然高分子材料、ポリグリコール酸、ポリ乳酸、ポリロイシン等の合成高分子材料であればよい。 Furthermore, the main body may contain a biodegradable polymer material. In this case, since the biodegradable polymer material has elasticity, elasticity can be added to the main body. Therefore, even if a force for deforming the main body is applied from the outside, it can be relaxed by elastic deformation, and the strength can be increased as compared with the case where no polymer material is included.
The biodegradable polymer material may be a natural polymer material such as gelatin, hyaluronic acid, fibrin, alginic acid, or chitin-chitosan, or a synthetic polymer material such as polyglycolic acid, polylactic acid, or polyleucine.

本体５を製造する際、原料の製造工程（Ｓ０１）では、直径１μｍ未満のβ−ＴＣＰを含む粉末にバインダとして非イオン性の水溶性セルロースエーテル系であるメチルセルロースやヒドロキシプロピルメチルセルロースを水と混ぜて原料を作製した。
成形工程（Ｓ０２）では、焼結後の貫通孔２の大きさが、直径１．５ｍｍ又は一辺１．５ｍｍから１０ｍｍとなるような金型を使用した。
乾燥工程（Ｓ０３）では、５００℃で１時間、還元焼成を数回行うとともに、水分を多く含むため、電子線などを利用した装置を用いて２００℃程度で乾燥させた。
顆粒体６を詰める工程（Ｓ０４）では、気孔径１００〜４００μｍを確保するために１．０ｍｍ以上１０ｍｍ以下となる顆粒体６を使用して貫通孔２内に詰めた。
焼結工程（Ｓ０５）では、１０５０℃の温度で１時間加熱して焼結した。
こうして得られた骨補填材１の圧縮強度は、図９に示すように顆粒体６を詰めない場合の１０〜１５ＭＰａに比べて、３０〜５０ＭＰａとなって３倍程度強度を高めることができた。 When manufacturing the main body 5, in the raw material manufacturing step (S01), nonionic water-soluble cellulose ether-based methylcellulose or hydroxypropylmethylcellulose is mixed with water as a binder in a powder containing β-TCP having a diameter of less than 1 μm. The raw material was produced.
In the molding step (S02), a mold was used in which the size of the through-hole 2 after sintering was 1.5 mm in diameter or 1.5 mm to 10 mm on a side.
In the drying step (S03), reduction firing was performed several times at 500 ° C. for 1 hour, and since it contained a lot of moisture, it was dried at about 200 ° C. using an apparatus using an electron beam or the like.
In the step of packing the granules 6 (S04), the granules 6 having a diameter of 1.0 mm or more and 10 mm or less were used to fill the through holes 2 in order to secure a pore diameter of 100 to 400 μm.
In the sintering step (S05), sintering was performed by heating at a temperature of 1050 ° C. for 1 hour.
The compressive strength of the bone filling material 1 obtained in this way was 30-50 MPa compared to 10-15 MPa when the granules 6 were not filled as shown in FIG. .

こうして得られた骨補填材１を用いて、骨補填体としてラットの培養骨を作製した。
まず、ラットから骨髄細胞を採取し、Ｔ型フラスコで１０日間初期培養を行うことによって不要成分を除去して十分な数の骨髄間葉系幹細胞を含む培養細胞を生成し、骨補填材１に播種した。骨芽細胞への分化誘導因子デキサメタゾンを加えて幹細胞の分化を開始しさらに２週間程度培養した。
こうして、骨髄間葉系幹細胞から分化した骨芽細胞を備える骨補填体を得た。
この骨補填体をラットの皮下に移植し、４週間後に再び取り出したところ、新しい骨組織の形成を確認することができた。 Using the bone grafting material 1 thus obtained, cultured bones of rats were produced as bone grafts.
First, bone marrow cells are collected from rats, and initial culture is performed in a T-shaped flask for 10 days to remove unnecessary components to generate cultured cells containing a sufficient number of bone marrow mesenchymal stem cells. Sowing. Differentiation-inducing factor dexamethasone into osteoblasts was added to initiate stem cell differentiation, and further cultured for about 2 weeks.
Thus, a bone complement comprising osteoblasts differentiated from bone marrow mesenchymal stem cells was obtained.
When this bone substitute was transplanted subcutaneously into a rat and removed again after 4 weeks, formation of new bone tissue could be confirmed.

本発明に係る第１の実施形態における骨補填材を示す一部断面を含む斜視図である。It is a perspective view including the partial cross section which shows the bone grafting material in 1st Embodiment which concerns on this invention. 本発明に係る第１の実施形態における骨補填材の本体を示す斜視図である。It is a perspective view which shows the main body of the bone grafting material in 1st Embodiment which concerns on this invention. 本発明に係る第１の実施形態における骨補填材の製造方法を示すフローチャートである。It is a flowchart which shows the manufacturing method of the bone grafting material in 1st Embodiment based on this invention. 本発明に係る第１の実施形態における骨補填材の他の例を示す一部断面を含む斜視図である。It is a perspective view including the partial cross section which shows the other example of the bone grafting material in 1st Embodiment which concerns on this invention. 本発明に係る第１の実施形態における骨補填材の他の例を示す一部断面を含む斜視図である。It is a perspective view including the partial cross section which shows the other example of the bone grafting material in 1st Embodiment which concerns on this invention. 本発明に係る第２の実施形態における骨補填材の本体を示す斜視図である。It is a perspective view which shows the main body of the bone grafting material in 2nd Embodiment which concerns on this invention. 本発明に係る他の実施形態における骨補填材の本体を示す斜視図である。It is a perspective view which shows the main body of the bone grafting material in other embodiment which concerns on this invention. 本発明に係る他の実施形態における骨補填材の本体を示す斜視図である。It is a perspective view which shows the main body of the bone grafting material in other embodiment which concerns on this invention. 本発明に係る第１の実施形態における骨補填材の実施例として圧縮強度を示すグラフである。It is a graph which shows compressive strength as an Example of the bone grafting material in 1st Embodiment which concerns on this invention.

符号の説明Explanation of symbols

１、７、１１、１３ 骨補填材（生体組織補填材）
２、１０、１２ 貫通孔
３ 隔壁
６ 顆粒体（多孔質部材）
８Ａ 一部の隔壁（隔壁）
８Ｂ 他の隔壁（隔壁）
1, 7, 11, 13 Bone filling material (living tissue filling material)
2, 10, 12 Through hole 3 Partition 6 Granule (porous member)
8A Some partitions (partitions)
8B Other partition walls (partition walls)

Claims (4)

複数の貫通孔がリン酸カルシウムを含む隔壁によって相互に区画されたハニカム形状の本体を備え、
少なくとも一つの前記貫通孔にリン酸カルシウムを含む多孔質部材が詰められていることを特徴とする生体組織補填材。 A plurality of through-holes are provided with a honeycomb-shaped main body partitioned from each other by partition walls containing calcium phosphate,
A biological tissue filling material, wherein at least one through-hole is filled with a porous member containing calcium phosphate. 前記本体が生分解性高分子材料を含むことを特徴とする請求項１に記載の生体組織補填材。   The biological tissue filling material according to claim 1, wherein the main body includes a biodegradable polymer material. 少なくとも一部の前記隔壁の厚さが他の前記隔壁の厚さと異なっていることを特徴とする請求項１又は２に記載の生体組織補填材。   The biological tissue filling material according to claim 1 or 2, wherein the thickness of at least a part of the partition walls is different from the thickness of the other partition walls. リン酸カルシウムを含む粉末にバインダを混入して原料を製造する工程と、
前記原料から複数の貫通孔が隔壁によって相互に区画されたハニカム成形体を製造する工程と、
前記ハニカム成形体を乾燥する工程と、
前記貫通孔に多孔質部材を詰める工程と、
前記ハニカム成形体を焼結する工程とを備えていることを特徴とする生体組織補填材の製造方法。

A step of manufacturing a raw material by mixing a binder with powder containing calcium phosphate;
Producing a honeycomb molded body in which a plurality of through holes are partitioned from each other by partition walls from the raw material;
Drying the honeycomb formed body,
Filling the through hole with a porous member;
And a step of sintering the honeycomb formed body.

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007105186A (en) * 2005-10-12 2007-04-26 Univ Nagoya Tissue-engineered bone composition
JP2010173906A (en) * 2009-01-30 2010-08-12 Pilot Corporation Ceramic structure

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JPH04303450A (en) * 1990-12-19 1992-10-27 Anton Haerle Bone substitute and its production
JPH07303692A (en) * 1991-08-27 1995-11-21 Torao Otsuka Tube net fabric composition weaved and knitted with biosoluble fiber and filled with hydroxyapatite
US5769897A (en) * 1991-12-13 1998-06-23 Haerle; Anton Synthetic bone
JP2002282285A (en) * 2001-03-23 2002-10-02 Olympus Optical Co Ltd Artificial bone material
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Publication number Priority date Publication date Assignee Title
JPH0280361A (en) * 1988-09-15 1990-03-20 Asahi Optical Co Ltd Orientable calcium phosphate compound molding and sintered body and their production
JPH04303450A (en) * 1990-12-19 1992-10-27 Anton Haerle Bone substitute and its production
JPH07303692A (en) * 1991-08-27 1995-11-21 Torao Otsuka Tube net fabric composition weaved and knitted with biosoluble fiber and filled with hydroxyapatite
US5769897A (en) * 1991-12-13 1998-06-23 Haerle; Anton Synthetic bone
JP2002282285A (en) * 2001-03-23 2002-10-02 Olympus Optical Co Ltd Artificial bone material
WO2003082160A1 (en) * 2002-03-30 2003-10-09 Mathys Medizinaltechnik Ag Surgical implant

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007105186A (en) * 2005-10-12 2007-04-26 Univ Nagoya Tissue-engineered bone composition
JP2010173906A (en) * 2009-01-30 2010-08-12 Pilot Corporation Ceramic structure

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