JP2012187186A - Base material sheet for regenerative medicine - Google Patents
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本発明は再生医療用基材シートに関する。より詳細には、表面及び／又は内部にコラーゲンの層を形成してなる生体内分解吸収性材料からなるメッシュ織物であって、人工皮膚、人工器官、人工臓器などに利用される再生医療用基材シートに関する。 The present invention relates to a regenerative medical base sheet. More specifically, it is a mesh fabric made of a biodegradable and absorbable material having a collagen layer formed on the surface and / or inside thereof, and is a regenerative medical substrate used for artificial skin, artificial organs, artificial organs, etc. The material sheet.
生体組織などに異常が生じたり、機能不全となった場合に、人工物をもってそれを代替することは古くから考えられていた。このような医用材料においては、生体親和性のあること、血液などの体液や組織に対する適合性があること、毒性や抗原性のないこと、移植部位によっては所定の機械的強度のあることなどの種々の条件が要求される。一般に、移植後、所期の目的を達成したのちには、生体に吸収されるか又は生体と同化するものが好ましいとされている。 For a long time, it has been considered to substitute an artificial object when an abnormality or a malfunction occurs in a living tissue. In such medical materials, there are biocompatibility, compatibility with body fluids and tissues such as blood, non-toxicity and antigenicity, and certain mechanical strength depending on the implantation site. Various conditions are required. In general, after achieving the intended purpose after transplantation, those that are absorbed into the body or assimilated with the body are preferred.
生体由来材料であるコラーゲンは生体親和性及び組織適合性に優れ、抗原性が低く、更に生体内で安全に吸収されることから、理想的な医用材料素材と考えられており、これを用いた医用材料がさまざま研究されている。コラーゲンは上記の特性のほか、細胞培養の培地として利用されているように宿主細胞の伸展・増殖を促進させる作用を有し、この点からも好ましい素材と考えられている。更に、コラーゲンを多孔質状としたコラーゲンスポンジはコラーゲンの層内に細胞が侵入し、活発に増殖して組織の再生を図ることができるので有用な材料であり、既に創傷治癒などに利用できることが明らかになっている。 Collagen, a bio-derived material, is considered to be an ideal medical material material because it has excellent biocompatibility and tissue compatibility, has low antigenicity, and is safely absorbed in vivo. Various medical materials have been studied. In addition to the above properties, collagen has an action of promoting the growth and proliferation of host cells as used as a cell culture medium, and is considered to be a preferable material from this point. Furthermore, collagen sponge made of collagen is a useful material because cells can penetrate into the collagen layer and actively proliferate to regenerate the tissue, and can be used for wound healing and the like. It has become clear.
しかし、コラーゲンスポンジは機械的強度が低く、コラーゲン単独では、細胞侵入性や増殖性が高く且つある程度の機械的強度を有する材料に成形することが困難である。そのため、従来は、シリコーンなどの合成高分子材料との複合材料として使用されていたが、このような材料を生体内に移植すると、合成高分子材料が異物として生体内に残存し、組織反応を起すなどの障害をもたらすことが多かった。 However, collagen sponge has low mechanical strength, and collagen alone is difficult to be molded into a material having high cell penetration and proliferation properties and a certain level of mechanical strength. Therefore, conventionally, it was used as a composite material with a synthetic polymer material such as silicone. However, when such a material is transplanted into a living body, the synthetic polymer material remains in the living body as a foreign substance and causes tissue reaction. It often caused obstacles such as waking up.
この様な問題を解決するものとして、例えば特許文献１には、生体内分解吸収性材料の表面にコラーゲンの層が形成されてなる医用材料が開示されており、実施例では、生体内分解吸収性材料からなる不織布の表面に多孔質状のコラーゲンを被覆している。しかし、この場合、複合化されるコラーゲンの厚みや細孔分布にバラツキが生じやすく、その結果、播種された細胞の増殖等にもバラツキが生じるおそれがある。
As a solution to such a problem, for example,
本発明の目的は上記の問題を解決することにある。
本発明者らは上記問題点を解決すべく鋭意検討した結果、選択された寸法特性をもつ生体内分解吸収性基材を用いることによって、複合化されるコラーゲンの層の厚みなどのバラツキを抑え、播種される細胞の増殖性等にも優れた再生医療用基材シートが得られることを知見し、本発明に到達した。
An object of the present invention is to solve the above problems.
As a result of intensive studies to solve the above problems, the present inventors have suppressed the variation such as the thickness of the collagen layer to be combined by using a biodegradable absorbent base material having a selected dimensional characteristic. The present inventors have found that a regenerative medical base sheet excellent in the proliferation property of cells to be seeded can be obtained, and reached the present invention.
本発明は、第１に、開孔率が１５〜５０％である生体内分解吸収性材料からなるメッシュ織物と、前記メッシュ織物の表面及び／又は内部に形成されたコラーゲンの層とからなる再生医療用基材シートである。 The present invention, firstly, is a regeneration comprising a mesh fabric made of a biodegradable absorbent material having a porosity of 15 to 50%, and a collagen layer formed on and / or inside the mesh fabric. It is a medical base material sheet.
本発明は、第２に、メッシュ織物の開口幅がタテ方向、ヨコ方向とも２００〜５００μｍである上記第１に記載の再生医療用基材シートである。 2ndly, this invention is a base sheet for regenerative medicine as described in said 1st whose opening width of a mesh fabric is 200-500 micrometers in a length direction and a horizontal direction.
本発明は、第３に、メッシュ織物開口幅のタテ方向とヨコ方向の比が０．６０〜１．４０である上記第２に記載の再生医療用基材シートである。 3rdly, this invention is a base material sheet | seat for regenerative medicine as described in said 2 whose ratio of the length direction of a mesh textile fabric opening width and a horizontal direction is 0.60-1.40.
本発明は、第４に、生体内分解吸収性材料が、ポリ−Ｌ−乳酸、ポリ−Ｄ−乳酸、ポリグリコール酸、グリコール酸と乳酸との共重合体、又は、ポリグリコール酸とポリ乳酸の混合物から選ばれる一種以上である上記第１乃至上記第３のいずれかに記載の再生医療用基材シートである。 In the present invention, fourthly, the biodegradable absorbent material is poly-L-lactic acid, poly-D-lactic acid, polyglycolic acid, a copolymer of glycolic acid and lactic acid, or polyglycolic acid and polylactic acid. The base sheet for regenerative medicine according to any one of the first to third aspects, wherein the base sheet is one or more selected from the above mixture.
本発明は、第５に、コラーゲンの層が、多孔質状である上記第１乃至第４のいずれかに記載の再生医療用基材シートである。 Fifthly, the present invention provides the base sheet for regenerative medicine according to any one of the first to fourth aspects, wherein the collagen layer is porous.
本発明の再生医療用基材シートは、開孔率が１５〜５０％である生体内分解吸収性材料からなるメッシュ織物と、前記メッシュ織物の表面及び／又は内部に形成されたコラーゲンの層とからなり、この基材シートは細胞を生体外で培養する際において、コラーゲンの層との複合化性がよく、また、コラーゲンの層が均一に形成されるため、播種された細胞が均一に定着・増殖しやすく、また、培養した組織を生体内に移植した際にも効率よく自己修復が行われる。その間、生体内分解吸収性材料は機械的強度を維持し、自己修復を支持する。そして、移植の目的が達成された後には、コラーゲン及び生体内分解吸収性材料は吸収され、生体内に異物として残存することがないので、従来の合成高分子材料のように肉芽形成、炎症などの障害を生ずるおそれがない。従って、本発明によれば、極めて安全性が高く且つ利用範囲の広い医用材料を得ることができるという効果を奏する。 The base sheet for regenerative medicine of the present invention comprises a mesh fabric made of a biodegradable and absorbable material having a porosity of 15 to 50%, and a collagen layer formed on the surface and / or inside of the mesh fabric. This base sheet has a good complexability with the collagen layer when cells are cultured in vitro, and the collagen layer is uniformly formed, so that the seeded cells are uniformly fixed. -It is easy to proliferate, and self-repair is performed efficiently when the cultured tissue is transplanted in vivo. Meanwhile, the biodegradable absorbable material maintains mechanical strength and supports self-healing. After the purpose of transplantation is achieved, collagen and biodegradable and absorbable materials are absorbed and do not remain as foreign substances in the living body, so granulation, inflammation, etc., as with conventional synthetic polymer materials There is no risk of causing trouble. Therefore, according to the present invention, it is possible to obtain a medical material that is extremely safe and has a wide range of use.
本発明の再生医療用シート基材は、開孔率が１５〜５０％である生体内分解吸収性材料からなるメッシュ織物と、前記メッシュ織物の表面及び／又は内部に形成されたコラーゲンの層とからなるものである。積層するコラーゲンの層は多孔質状に形成されているものが好ましく、またコラーゲンとしては抗原性が低減されたアルカリ可溶化コラーゲン又は酵素可溶化コラーゲンが好ましい。 The sheet base material for regenerative medicine of the present invention comprises a mesh fabric made of a biodegradable absorbent material having a porosity of 15 to 50%, and a collagen layer formed on the surface and / or inside of the mesh fabric. It consists of The collagen layer to be laminated is preferably formed in a porous shape, and the collagen is preferably alkali-solubilized collagen or enzyme-solubilized collagen with reduced antigenicity.
本発明において、用いられる生体内分解吸収性材料としては、生体内で加水分解、酵素分解などにより分解し吸収され、所望の機械的強度を有するものであれば種々の材料を用いることができるが、好適にはポリ−Ｌ−乳酸、ポリ−Ｄ−乳酸、ポリグリコール酸、グリコール酸と乳酸との共重合体、又は、ポリグリコール酸とポリ乳酸の混合物などが挙げられる。 In the present invention, as the biodegradable and absorbable material used in the present invention, various materials can be used as long as they are decomposed and absorbed in vivo by hydrolysis, enzymatic degradation, etc. and have a desired mechanical strength. Preferable examples include poly-L-lactic acid, poly-D-lactic acid, polyglycolic acid, a copolymer of glycolic acid and lactic acid, or a mixture of polyglycolic acid and polylactic acid.
本発明では、組織の安定性、強度やコラーゲンの層との密着性の点から、上記した生体内分解性材料からなる組織を用いたメッシュ織物が用いられる。
その開口率は１５〜５０％であることが必要である。この場合、開口率は、（タテ糸間の間隔×ヨコ糸間の間隔）／（（タテ糸間の間隔＋糸径）＊（ヨコ糸間の間隔＋糸径））で算出される。開口率が１５％未満であると、メッシュ織物とコラーゲンの層と十分な複合化がなされないおそれがあり、５０％より大きいと、支持体として十分な強度を保持できなくなるおそれがある。
In the present invention, a mesh fabric using a tissue composed of the above-described biodegradable material is used from the viewpoint of tissue stability, strength, and adhesion to a collagen layer.
The aperture ratio needs to be 15 to 50%. In this case, the aperture ratio is calculated by (interval between warp yarns × interval between weft yarns) / ((interval between warp yarns + thread diameter) * (interval between weft yarns + thread diameter)). If the opening ratio is less than 15%, the mesh fabric and the collagen layer may not be sufficiently combined, and if it exceeds 50%, sufficient strength as a support may not be maintained.
また、そのメッシュ織物の開口幅はタテ方向、ヨコ方向とも２００〜５００μｍであることが好ましい。開口幅が２００μｍ未満であるとコラーゲンの層と十分な複合化が不可能なおそれがあり、５００μｍより大きいと支持体として十分な強度を保持できなくなるおそれや、ホツレのおそれがある。 The opening width of the mesh fabric is preferably 200 to 500 μm in both the vertical and horizontal directions. If the opening width is less than 200 μm, there is a possibility that sufficient complexation with the collagen layer may not be possible. If the opening width is more than 500 μm, sufficient strength as a support may not be maintained, and there is a risk of fraying.
また、メッシュ織物の開口幅のタテ方向とヨコ方向の比は０．６０〜１．４０であることが好ましい。メッシュ織物開口幅のタテ方向とヨコ方向の比が範囲外であると、開口部形状が不均一な形状になり、コラーゲンの層との複合化が不均一になるおそれがある。 Moreover, it is preferable that the ratio of the opening width of the mesh fabric in the vertical direction and the horizontal direction is 0.60 to 1.40. If the ratio of the mesh fabric opening width between the vertical direction and the horizontal direction is out of the range, the shape of the opening becomes non-uniform, and the composite with the collagen layer may be non-uniform.
尚、本発明において、上記した開口率、開口幅及び開口幅のタテ方向とヨコ方向の比と幅をもって記載したが、個々のメッシュ織物においては、それぞれの値は実質上単一の値を示すものである。 In the present invention, the aperture ratio, the aperture width, and the ratio of the width and the width of the aperture width and the width and the width are described, but in each mesh fabric, each value is substantially a single value. Is.
また、本発明のメッシュ織物は、生体組織やコラーゲン溶液との親和性を高めるため、親水化処理を行うことができる。親水化処理としてはプラズマ照射などが挙げられる。 In addition, the mesh fabric of the present invention can be subjected to a hydrophilization treatment in order to increase the affinity with a living tissue or a collagen solution. Examples of the hydrophilic treatment include plasma irradiation.
また、本発明のメッシュ織物は、保水性を有することが好ましい。コラーゲンの層は、後述するように、その製造過程においてコラーゲン水溶液を使用するため、前記メッシュ織物が保水性を有することにより、メッシュ織物とコラーゲンの層が安定的に複合化されると考えられる。保水性は一般に水との接触角で判断され、接触角が大きいほど保水性に優れると言える。そのためメッシュ織物と水との接触角は１００°以上であることが好ましい。なお、理由は定かではないが、保水性は、開口率、開口幅に関係すると思われる。 Moreover, it is preferable that the mesh fabric of this invention has water retention. As will be described later, since the collagen layer uses a collagen aqueous solution in the production process, it is considered that the mesh fabric and the collagen layer are stably combined when the mesh fabric has water retention. The water retention is generally determined by the contact angle with water, and it can be said that the greater the contact angle, the better the water retention. Therefore, the contact angle between the mesh fabric and water is preferably 100 ° or more. Although the reason is not clear, water retention is considered to be related to the aperture ratio and the aperture width.
本発明の再生医療用基材シートは、上述のように生体内分解吸収性材料からなるメッシュ織物の表面及び／又は内部にコラーゲンの層が形成される。コラーゲンの層は、メッシュ織物の一面のみに形成してもよく、また両面に形成してもよい。コラーゲンの層の原料となるコラーゲンとしては、従来用いられている各種コラーゲンを用いることができ、例えば、中性塩可溶性コラーゲン、酸可溶性コラーゲン、アルカリ可溶化コラーゲン、酵素可溶化コラーゲンなどが挙げられる。これらのうち、アルカリ可溶化コラーゲン及び酵素可溶化コラーゲンは、不溶性コラーゲンを、それぞれアルカリ処理又は酵素（例えば、ペプシン、トリプシン、キモトリプシン、パパイン、プロナーゼ等）処理したもので、抗原性が低減されているので、好適に使用される。上記のコラーゲンの由来は特に限定されず、一般に哺乳動物（例えば、ウシ、ブタ、ウサギ、ヒツジ、ネズミ等）の皮膚、骨、軟骨、腱、臓器などから得られるコラーゲンが用いられる。また、魚類、鳥類などから得られるコラーゲン様蛋白も用いることができる。 The base sheet for regenerative medicine of the present invention has a collagen layer formed on the surface and / or inside of a mesh fabric made of a biodegradable absorbent material as described above. The collagen layer may be formed on only one side of the mesh fabric or on both sides. As the collagen used as the raw material for the collagen layer, various conventionally used collagens can be used. Examples thereof include neutral salt-soluble collagen, acid-soluble collagen, alkali-solubilized collagen, and enzyme-solubilized collagen. Among these, alkali-solubilized collagen and enzyme-solubilized collagen are obtained by treating insoluble collagen with alkali or enzyme (for example, pepsin, trypsin, chymotrypsin, papain, pronase, etc.), respectively, and have reduced antigenicity. Therefore, it is preferably used. The origin of the collagen is not particularly limited, and generally collagen obtained from the skin, bone, cartilage, tendon, organ, etc. of mammals (eg, cows, pigs, rabbits, sheep, mice, etc.) is used. In addition, collagen-like proteins obtained from fish, birds and the like can also be used.
本発明の再生医療用基材シートにおいて、メッシュ織物とコラーゲンの層の複合化は、コラーゲン溶液の塗布、流し込みなどの従来公知の方法にて、メッシュ織物の表面及び／又は内部にコラーゲン溶液による層を形成し、次いで凍結乾燥などの手段によりコラーゲン溶液層を固層化させることにより形成することができる。凍結乾燥は常法に準じて行うことができる。この際、コラーゲンの層の強度を高めるため、凍結乾燥に先立ち、コラーゲンを線維化しておくのが好ましく、この線維化は、コラーゲン溶液のｐＨの変化（例えば、酸性溶液の中和等）、温度上昇などにより行うことができる。 In the base sheet for regenerative medicine of the present invention, the mesh fabric and the collagen layer are combined by a conventionally known method such as coating or pouring of a collagen solution, and the layer of the collagen fabric on the surface and / or inside of the mesh fabric. And then solidifying the collagen solution layer by means such as freeze-drying. Freeze-drying can be performed according to a conventional method. At this time, in order to increase the strength of the collagen layer, it is preferable that the collagen is fibrillated prior to freeze-drying. This fibrillation is caused by changes in the pH of the collagen solution (for example, neutralization of an acidic solution), temperature, etc. This can be done by ascending.
コラーゲン溶液層の厚さは、最終的に固層化したコラーゲンの層の厚さが０．５μｍ〜２０ｍｍ程度、好ましくは１〜１０ｍｍとなるように調整されることが好ましい。コラーゲンの層の厚さが０．５μｍ未満であると、生体内でのコラーゲンの吸収が速く、十分な効果が得られず、また２０ｍｍを超えても効果的には格別の問題はないが、作業性などの点で問題を生ずるおそれがある。ここで使用されるコラーゲン溶液の濃度は、所望するコラーゲンの層の厚さ、密度などにより適宜調整することができるが、１×１０−２〜３×１０２ｍｇ／ｍＬが好ましい。 The thickness of the collagen solution layer is preferably adjusted so that the finally solidified collagen layer has a thickness of about 0.5 μm to 20 mm, preferably 1 to 10 mm. When the thickness of the collagen layer is less than 0.5 μm, the absorption of collagen in the living body is fast, and a sufficient effect cannot be obtained, and even if it exceeds 20 mm, there is no particular problem effectively. There is a risk of problems in terms of workability. Although the density | concentration of the collagen solution used here can be suitably adjusted with the thickness of the layer of desired collagen, a density, etc., 1 * 10 <-2 > -3 * 10 < 2 > mg / mL is preferable.
コラーゲンの層は、生体内に移植したときに細胞の侵入・伸展・増殖が容易になるように、多孔質状に形成するのが好ましい。この際、コラーゲンの層を多孔質状（スポンジ状）とする場合には、コラーゲン溶液は撹拌して起泡させたものも用いることができる。 The collagen layer is preferably formed in a porous shape so that cells can be easily invaded, spread and proliferated when transplanted into a living body. At this time, when the collagen layer is made porous (sponge), the collagen solution that has been agitated and foamed can also be used.
前記コラーゲンの層は、生体に移植した際のコラーゲンの吸収が早すぎないように、必要に応じてコラーゲンを架橋処理するのが好ましい。コラーゲンの架橋処理は、架橋剤を用いる方法、γ線照射による方法、紫外線照射による方法や加熱処理による方法などが挙げられる。 The collagen layer is preferably subjected to a crosslinking treatment as necessary so that the collagen is not absorbed too quickly when transplanted into a living body. Examples of the collagen crosslinking treatment include a method using a crosslinking agent, a method using γ-ray irradiation, a method using ultraviolet irradiation, and a method using heat treatment.
本発明の再生医療用基材シートは、従来から検討されている各種の皮膚、靱帯、血管、臓器などに応用することができ、生体内で分解吸収されるので、特に生体内に埋設される人工器官、人工臓器などに好適に用いられる。また、縫合面の補強などにも利用することができる。 The base sheet for regenerative medicine of the present invention can be applied to various types of skin, ligaments, blood vessels, organs, and the like that have been studied in the past, and is especially embedded in the living body because it is decomposed and absorbed in the living body. It is suitably used for artificial organs, artificial organs and the like. It can also be used to reinforce the stitching surface.
〔実施例〕
以下実施例に基づいて詳細に説明する。ただし、本発明は以下の実施例に限定されるものではない。また、評価方法は以下の通りである。
〔開口幅、開口率〕
メッシュ織物をマイクロスコープにて１００倍に拡大し、タテ糸間の間隔（タテ方向開口幅）、ヨコ糸間の間隔（ヨコ方向開口幅）及び糸径を測定し、
（タテ糸間の間隔×ヨコ糸間の間隔）／（（タテ糸間の間隔＋糸径）＊（ヨコ糸間の間隔＋糸径））×１００ にて算出した。
〔メッシュ織物の開孔幅の（タテ方向・ヨコ方向）の比〕
上記で測定したタテ糸間の間隔とヨコ糸間の間隔から、
（タテ糸間の間隔）／（ヨコ糸間の間隔）で算出した。
〔メッシュ織物の保水性〕
動的接触性測定システム（共和界面化学（株）製 ＤＣＡ−ＷＺ）にメッシュ織物をセットし、３μｌの水を滴下し、水滴とメッシュ織物の接触角θを測定し、下記のように判断した。
保水性良 θ≧１００°
保水性不良 θ＜１００°
〔コラーゲンの層の状態〕
作成した再生医療基材シートの表面及び側面を走査型電子顕微鏡で１０００倍で撮影し、コラーゲンの層表面の細孔のバラツキと厚みを確認した。
○ 無孔部分も認められず、細孔部分は均一に分布しおり、厚みもそろっていた。
× 無孔部分が認められる、或いは、細孔分布に多少のバラツキが見られる、或いは、厚みにバラツキが見られる。
〔Example〕
Hereinafter, it demonstrates in detail based on an Example. However, the present invention is not limited to the following examples. The evaluation method is as follows.
[Aperture width, aperture ratio]
Magnify the mesh fabric 100 times with a microscope, measure the spacing between the warp yarns (vertical direction opening width), the spacing between the horizontal yarns (horizontal direction opening width) and the yarn diameter,
(Spacing between warp yarns × Spacing between weft yarns) / ((Spacing between warp yarns + Thread diameter) * (Spacing between weft yarns + Thread diameter)) × 100
[Ratio of mesh fabric opening width (vertical / horizontal)]
From the spacing between the warp and the weft measured above,
It was calculated by (interval between warp yarns) / (interval between weft yarns).
[Water retention of mesh fabric]
A mesh fabric was set on a dynamic contact measurement system (DCA-WZ, manufactured by Kyowa Interface Chemical Co., Ltd.), 3 μl of water was dropped, the contact angle θ between the water droplet and the mesh fabric was measured, and judged as follows. .
Good water retention θ ≧ 100 °
Poor water retention θ <100 °
[Collagen layer state]
The surface and side surfaces of the prepared regenerative medical base sheet were photographed with a scanning electron microscope at a magnification of 1000 to confirm the variation and thickness of the pores on the surface of the collagen layer.
○ No pores were observed, the pores were uniformly distributed, and the thickness was uniform.
X Non-porous portions are observed, or there is some variation in pore distribution, or there is variation in thickness.
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）をＺ５６０Ｔ／Ｍで追撚したものを経糸及び緯糸に用いて、経密度４５本／インチ、緯密度４５本／インチの平組織からなるメッシュ織物を製織した。この織物の開口率は４４％で、タテ方向のメッシュ開口幅が４３０μｍ、ヨコ方向のメッシュ開口幅が４３０μｍ、線径２１４μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は１．００であった。
次に、メッシュ織物とコラーゲンの層（コラーゲンスポンジ）との複合化の方法を示す。まず、銅板をパラフルオロアルコキシ（ＰＦＡ）フィルムで包み、その表面に純水を２０回噴霧し、これを−３０℃で凍結することにより、平均粒径４００μｍの氷微粒子を作製した。次に、作製した氷微粒子の鋳型を−３℃の低温チャンバー内に1時間静置し、氷微粒子の温度を−３℃に保持した。一方、１．０（ｗ／ｖ）％ブタタイプＩコラーゲン水溶液を−１℃で２４時間静置した。コラーゲンスポンジの厚みを制御するために、厚さが１．０ｍｍのシリコーンフレームを用いた。−３℃の低温チャンバー内で、氷微粒子の鋳型の上にシリコーンフレームを載せ、フレームの中に上記のコラーゲン水溶液を流し込み、メッシュ織物とポリ塩化ビニリデンラップで覆ったガラスプレートを順にコラーゲン水溶液の上に載せて−３℃で1時間凍結した。さらに−８０℃で５時間凍結した後、ポリ塩化ビニリデンラップで覆ったガラスプレートを除いて凍結物を銅板から外し、これを２４時間凍結乾燥し、メッシュ織物とコラーゲンの層との複合体を得た。該複合体を２５％グルタルアルデヒド水溶液で飽和した蒸気中で４時間処理しコラーゲンを架橋させた。その後、該複合体を純水で３回洗浄し、０．１Ｍグリシン水溶液に１２時間浸漬することにより、未反応のアルデヒド基をブロッキングした。その後、純水で６回洗浄した。洗浄した複合体を凍結乾燥し、再生医療用基材シートを作成した。評価結果を表１に示す。
A mesh woven fabric having a warp density of 45 yarns / inch and a weft density of 45 yarns / inch was woven using polylactic acid fibers 150 dtex30f (manufactured by Concordia Medical Co., Ltd.) twisted at Z560 T / M as warps and wefts. . The opening ratio of this woven fabric was 44%, the mesh opening width in the vertical direction was 430 μm, the mesh opening width in the horizontal direction was 430 μm, the wire diameter was 214 μm, and the ratio of the vertical and horizontal directions of the mesh opening width was 1.00. .
Next, a method of combining the mesh fabric and the collagen layer (collagen sponge) will be described. First, a copper plate was wrapped with a parafluoroalkoxy (PFA) film, and the surface was sprayed with pure water 20 times, and frozen at −30 ° C., thereby producing ice fine particles having an average particle diameter of 400 μm. Next, the produced ice fine particle mold was allowed to stand in a low temperature chamber at -3 ° C for 1 hour, and the temperature of the ice fine particles was maintained at -3 ° C. On the other hand, 1.0 (w / v)% porcine type I collagen aqueous solution was allowed to stand at -1 ° C for 24 hours. In order to control the thickness of the collagen sponge, a silicone frame having a thickness of 1.0 mm was used. In a low temperature chamber at -3 ° C, place a silicone frame on a mold of ice particles, pour the collagen aqueous solution into the frame, and sequentially place the glass plate covered with mesh fabric and polyvinylidene chloride wrap on the collagen aqueous solution. And frozen at -3 ° C for 1 hour. After further freezing at −80 ° C. for 5 hours, the frozen material was removed from the copper plate except for the glass plate covered with polyvinylidene chloride wrap, and this was freeze-dried for 24 hours to obtain a composite of mesh fabric and collagen layer. It was. The complex was treated in steam saturated with 25% aqueous glutaraldehyde solution for 4 hours to crosslink the collagen. Thereafter, the complex was washed with pure water three times and immersed in a 0.1 M glycine aqueous solution for 12 hours to block unreacted aldehyde groups. Thereafter, it was washed 6 times with pure water. The washed composite was lyophilized to prepare a regenerative medical base sheet. The evaluation results are shown in Table 1.
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（追撚無し）（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）を用いて経密度４５本／インチ、緯密度４２本／インチの平組織からなるメッシュ織物を製織した。この織物の開口率は１８％で、タテ方向のメッシュ開口幅が２１０μｍ、ヨコ方向のメッシュ開口幅が３２０μｍ、線径３４７μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は０．６６であった。次に、実施例１と同様にして、メッシュ織物とコラーゲンスポンジを積層し再生医療用基材シートを作成した。評価結果を表１に示す。 Using a polylactic acid fiber 150 dtex30f (without twist) (manufactured by Concordia Medical), a mesh fabric composed of a plain structure having a warp density of 45 / inch and a weft density of 42 / inch was woven. The opening ratio of this fabric was 18%, the mesh opening width in the vertical direction was 210 μm, the mesh opening width in the horizontal direction was 320 μm, the wire diameter was 347 μm, and the ratio of the vertical and horizontal directions of the mesh opening width was 0.66. . Next, in the same manner as in Example 1, a mesh fabric and a collagen sponge were laminated to prepare a regenerative medical base sheet. The evaluation results are shown in Table 1.
〔比較例１〕
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（追撚無し）（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）を用いて経密度６０本／インチ、緯密度６４本／インチの平組織からなるメッシュ織物を製織した。この織物の開口率は１．５％で、タテ方向のメッシュ開口幅が６５μｍ、ヨコ方向のメッシュ開口幅が１２０μｍ、線径６２７μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は０．５４であった。次に、実施例１と同様にしてメッシュ織物とコラーゲンスポンジを積層し再生医療用基材シートを作成した。評価結果を表１に示す。
[Comparative Example 1]
Using a polylactic acid fiber 150dtex30f (without twist) (manufactured by Concordia Medical), a mesh fabric having a plain structure with a warp density of 60 / inch and a weft density of 64 / inch was woven. The opening ratio of this fabric is 1.5%, the mesh opening width in the vertical direction is 65 μm, the mesh opening width in the horizontal direction is 120 μm, the wire diameter is 627 μm, and the ratio of the vertical and horizontal directions of the mesh opening width is 0.54. there were. Next, in the same manner as in Example 1, a mesh fabric and a collagen sponge were laminated to prepare a regenerative medical base sheet. The evaluation results are shown in Table 1.
〔比較例２〕
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（追撚無し）（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）を用いて経密度６０本／インチ、緯密度３１本／インチの平組織からなるメッシュ織物を製織した。この織物の開口率は１４％で、タテ方向のメッシュ開口幅が４３０μｍ、ヨコ方向のメッシュ開口幅が１２０μｍ、線径３２９μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は３．５８であった。次に、実施例１と同様にして、メッシュ織物とコラーゲンスポンジを積層し再生医療用基材シートを作成した。評価結果を表１に示す。
[Comparative Example 2]
Using a polylactic acid fiber 150 dtex30f (without twist) (manufactured by Concordia Medical), a mesh fabric composed of a plain structure with a warp density of 60 / inch and a weft density of 31 / inch was woven. The opening ratio of this fabric was 14%, the mesh opening width in the vertical direction was 430 μm, the mesh opening width in the horizontal direction was 120 μm, the wire diameter was 329 μm, and the ratio of the vertical and horizontal directions of the mesh opening width was 3.58. . Next, in the same manner as in Example 1, a mesh fabric and a collagen sponge were laminated to prepare a regenerative medical base sheet. The evaluation results are shown in Table 1.
〔比較例３〕
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（追撚無し）（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）を用いて経密度４５本／インチ、緯密度６４本／インチの平組織からなるメッシュ織物を製織した。この織物の開口率は７％で、タテ方向のメッシュ開口幅が６５μｍ、ヨコ方向のメッシュ開口幅が３００μｍ、線径３４１μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は０．２１であった。次に、実施例１と同様にして、メッシュ織物とコラーゲンスポンジを積層し再生医療用基材シートを作成した。評価結果を表１に示す。
[Comparative Example 3]
Using a polylactic acid fiber 150 dtex30f (without twist) (manufactured by Concordia Medical), a mesh fabric composed of a plain structure having a warp density of 45 / inch and a weft density of 64 / inch was woven. The opening ratio of this woven fabric was 7%, the mesh opening width in the vertical direction was 65 μm, the mesh opening width in the horizontal direction was 300 μm, the wire diameter was 341 μm, and the ratio of the vertical direction to the horizontal direction in the mesh opening width was 0.21. . Next, in the same manner as in Example 1, a mesh fabric and a collagen sponge were laminated to prepare a regenerative medical base sheet. The evaluation results are shown in Table 1.
〔比較例４〕
ポリ乳酸繊維１５０ｄｔｅｘ３０ｆ（追撚無し）（Ｃｏｎｃｏｒｄｉａ Ｍｅｄｉｃａｌ社製）を用いて経密度１２０本／インチ、緯密度８０本／インチの平組織からなる織物を製織した。この織物の開口率は０％で、タテ方向のメッシュ開口幅が０μｍ、ヨコ方向のメッシュ開口幅が０μｍ、線径２３７μｍ、メッシュ開口幅のタテ方向とヨコ方向の比は０であった。次に、実施例１と同様にして、平組織織物とコラーゲンスポンジを積層し再生医療用基材シートを作成した。評価結果を表１に示す。
[Comparative Example 4]
Using a polylactic acid fiber 150 dtex30f (without twist) (manufactured by Concordia Medical), a woven fabric having a plain structure with a warp density of 120 / inch and a weft density of 80 / inch was woven. The opening ratio of this woven fabric was 0%, the mesh opening width in the vertical direction was 0 μm, the mesh opening width in the horizontal direction was 0 μm, the wire diameter was 237 μm, and the ratio of the vertical direction to the horizontal direction in the mesh opening width was 0. Next, in the same manner as in Example 1, a plain tissue fabric and a collagen sponge were laminated to produce a regenerative medical base sheet. The evaluation results are shown in Table 1.
１．再生医療用基材シート
２．コラーゲンの層
３．メッシュ織物
1. 1. Regenerative
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