WO2010013717A1 - 血管再生基材 - Google Patents
血管再生基材 Download PDFInfo
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- WO2010013717A1 WO2010013717A1 PCT/JP2009/063438 JP2009063438W WO2010013717A1 WO 2010013717 A1 WO2010013717 A1 WO 2010013717A1 JP 2009063438 W JP2009063438 W JP 2009063438W WO 2010013717 A1 WO2010013717 A1 WO 2010013717A1
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- WIPO (PCT)
- Prior art keywords
- reinforcing
- foam
- blood vessel
- yarn
- base material
- Prior art date
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
Definitions
- the present invention relates to a blood vessel regeneration base material that can regenerate blood vessels with extremely high efficiency by being transplanted into a blood vessel defect.
- non-absorbable polymers such as Gore-Tex are used as artificial blood vessels in clinical practice. Such artificial blood vessels can exhibit physical properties very close to those of blood vessels, and have achieved certain results in short-term blood vessel reconstruction.
- an artificial blood vessel using a non-absorbable polymer has a problem that it is necessary to continuously administer an anticoagulant or the like because a foreign substance remains in the body semipermanently and thrombi easily form. It was. In particular, when used for children, there has been a problem that it is necessary to perform a new operation due to a size mismatch accompanying growth, and that a re-operation is required due to calcification of an artificial blood vessel.
- tissue regeneration methods using so-called regenerative medical techniques have been attempted.
- transplanting an artificial blood vessel with easy cell invasion into a blood vessel defect an attempt is made to regenerate its own tissue by utilizing the mechanism by which the patient's own cells proliferate using the artificial blood vessel as a scaffold. is there.
- a revascularized base material in which a reinforcing material made of a bioabsorbable polymer is incorporated as a core into a foam made of a bioabsorbable polymer.
- Patent Document 1 a vascular regeneration base material
- the foam serves as a scaffold to firmly adhere cells
- the reinforcing material plays a role to withstand blood flow and maintain strength during the period until the blood vessel regenerates after transplantation. It also serves as a tough reinforcement.
- both the foam and the reinforcing material are made of a bioabsorbable polymer, the material is absorbed after the blood vessel regeneration, so that continuous use of an anticoagulant or the like becomes unnecessary in the remote period. Furthermore, since the regenerated blood vessels are self-organized, growth can be expected. In fact, it has been confirmed that the revascularization base material is very significant clinically. However, it goes without saying that for actual clinical application, further revascularization efficiency and certainty should be aimed at.
- the vascular tissue can be regenerated when the artificial blood vessel is transplanted depends on the ease of cell invasion into the artificial blood vessel and the fact that stenosis does not occur until the vascular tissue is regenerated.
- the artificial blood vessel material is required to be flexible and have high water absorption.
- the proliferated cells exert tension in the lumen direction, stenosis occurs, so that the tube shape of the artificial blood vessel has a mechanical strength that does not easily collapse, that is, the tube shape When compressing the body, it is required to exhibit a high compression elastic modulus and maintain the aperture.
- the present invention provides a blood vessel regeneration base material that can regenerate blood vessels with extremely high efficiency by transplanting into a defective portion of a blood vessel while achieving both ease of cell invasion, resistance to crushing, and prevention of calcification. The purpose is to provide.
- the present invention relates to a tubular blood vessel comprising a foam made of a bioabsorbable material, a reinforcing material made of a bioabsorbable material that reinforces the foam, and a reinforcing thread made of a bioabsorbable material that reinforces the foam. It is a recycled substrate, wherein the reinforcing yarn and the reinforcing material are located at the center or outer surface of the foam, the inner surface is the foam, and the reinforcing yarn is spiral, ring-shaped or X-shaped.
- the reinforcing yarn is a vascular regeneration substrate made of glycolide- ⁇ -caprolactone copolymer.
- the blood vessel regeneration substrate of the present invention includes a foam made of a bioabsorbable material (hereinafter also simply referred to as “foam”), and a reinforcing material made of a bioabsorbable material that reinforces the foam (hereinafter simply referred to as “reinforcing material”). And a reinforcing yarn made of a bioabsorbable material that reinforces the foam (hereinafter also simply referred to as “reinforcing yarn”).
- foam made of a bioabsorbable material
- reinforcing material made of a bioabsorbable material that reinforces the foam
- reinforcing yarn made of a bioabsorbable material that reinforces the foam
- the foam serves as a scaffold for the invading cells to adhere and proliferate and the tissue to regenerate.
- the pore size of the foam needs to be such that cells easily invade and proliferate and hardly leak when blood is transplanted into a blood vessel defect.
- the preferred lower limit is 5 ⁇ m
- the preferred upper limit Is 100 ⁇ m. If the pore size of the foam is less than 5 ⁇ m, cells may not be able to enter the pores of the foam, and if it exceeds 100 ⁇ m, blood leakage may occur when transplanted.
- the more preferable lower limit of the pore diameter of the foam is 10 ⁇ m, and the more preferable upper limit is 50 ⁇ m.
- the average pore diameter of the foam can be measured by a conventionally known method such as a mercury intrusion method or an image analysis method.
- a preferable minimum is 0.3 mm and a preferable upper limit is 1.5 mm.
- the thickness of the foam is less than 0.3 mm, the compression elastic modulus when compressing the tube-like body may be low and may easily cause constriction.
- the thickness exceeds 1.5 mm the foam lacks flexibility and has a water absorption rate. It may be low and cells may be difficult to enter.
- the minimum with more preferable thickness of the said foam is 0.4 mm, and a more preferable upper limit is 1.2 mm.
- bioabsorbable material constituting the foam examples include polyglycolide, polylactide (D, L, DL form), polycaprolactone, glycolide-lactide (D, L, DL form) copolymer, glycolide- ⁇ - Examples include caprolactone copolymer, lactide (D, L, DL form) - ⁇ -caprolactone copolymer and polydioxanone, glycolide-lactide (D, L, DL form) - ⁇ -caprolactone copolymer. Among these, lactide (D, L, DL form) - ⁇ -caprolactone copolymer is preferable. These bioabsorbable materials may be used alone or in combination of two or more.
- the foam may be subjected to a hydrophilic treatment.
- a hydrophilic treatment By performing the hydrophilic treatment, the invasion of cells can be facilitated.
- the hydrophilization treatment is not particularly limited, and examples thereof include plasma treatment, glow discharge treatment, corona discharge treatment, ozone treatment, surface graft treatment, and ultraviolet irradiation treatment. Among these, plasma treatment is preferable because the water absorption can be dramatically improved without changing the appearance of the blood vessel regeneration substrate.
- the reinforcing material reinforces the foam and plays a role in resisting blood flow and intravascular pressure (blood pressure) during the period until the blood vessel is regenerated after transplantation, and threading property at the time of suturing with the blood vessel It plays a role of improving stitchability.
- the reinforcing material is not particularly limited as long as it has higher strength than the foamed material, and examples thereof include a fibrous material, a nonwoven fabric material, and a film material. Of these, fibrous bodies such as flat knitted fabrics, warp knitted fabrics, braids, and woven fabrics formed by weaving fibers made of bioabsorbable materials are preferable.
- bioabsorbable material constituting the reinforcing material examples include polyglycolide, polylactic acid (D, L, DL form), polycaprolactone, glycolide-lactide (D, L, DL form) copolymer, glycolide- ⁇ . -Caprolactone copolymer, lactide (D, L, DL form) - ⁇ -caprolactone copolymer and polydioxanone, glycolide-lactide (D, L, DL form) - ⁇ -caprolactone copolymer, and the like. These bioabsorbable materials may be used alone or in combination of two or more. Further, the bioabsorbable material constituting the reinforcing material may be the same as or different from the bioabsorbable material constituting the foam.
- a preferable minimum is 15 denier and a preferable upper limit is 500 denier. If the thickness of the fiber constituting the reinforcing material is less than 15 denier, the anastomosis may not be possible at the time of anastomosis with a living blood vessel, and if it exceeds 500 denier, the reinforcing material may not be produced. A more preferable lower limit of the thickness of the reinforcing material is 20 denier, and a more preferable upper limit is 450 denier.
- the reinforcing thread reinforces the foam and maintains the strength by resisting blood flow, lungs, compression from surrounding organs, and tension in the lumen direction until the blood vessel is regenerated after transplantation. It plays a role.
- the reinforcing yarn may be a monofilament yarn or a multifilament yarn, but a monofilament yarn is preferable because it has higher bending elasticity and can withstand a pressing force.
- the thickness of the reinforcing yarn is not particularly limited, but a preferable lower limit is 0.2 mm and a preferable upper limit is 0.7 mm. If the thickness of the reinforcing yarn is less than 0.2 mm, the compression elastic modulus when compressing the tube-like body may be low, and stenosis may occur easily. If the thickness exceeds 0.7 mm, the vascular regeneration group lacks flexibility. It may be difficult to use as a material. A more preferable lower limit of the thickness of the reinforcing yarn is 0.25 mm, and a more preferable upper limit is 0.5 mm.
- the bioabsorbable material constituting the reinforcing yarn is glycolide- ⁇ -caprolactone copolymer.
- Glycolide- ⁇ -caprolactone copolymer is a relatively “hard” resin with an elastic modulus of about 630 MPa, while the strength half-life degrades in a relatively short time of 1 to 2 weeks and rapidly decreases in strength.
- a reinforcing thread made of a glycolide- ⁇ -caprolactone copolymer sufficient strength can be maintained for a while from the time of transplantation, and the blood vessel regeneration base material can be prevented from being crushed and the blood vessels being narrowed. When it is regenerated, it decomposes and absorbs to lose its strength. Further, since no material remains, it is possible to prevent mineral deposition, thereby effectively preventing “calcification”.
- glycolide- ⁇ -caprolactone copolymer has a low affinity for the foam, and it is considered that the glycolide- ⁇ -caprolactone copolymer peels from the foam in a short period of time after transplantation in combination with decomposition in a relatively short time.
- a reinforcing thread made of a glycolide- ⁇ -caprolactone copolymer sufficient strength can be maintained for a while from the time of transplantation, and the vascular regeneration base material can be prevented from being crushed and the blood vessels narrowing, while the blood vessels are somewhat When it is recycled, it peels off from the foam.
- the reinforcing yarn Since the foam from which the reinforcing yarn has been peeled can expand and contract as the cells grow, the regeneration of blood vessels is not hindered. This also seems to have led to efficient prevention of “calcification”. The cause is unknown, but if the reinforcing yarn is coated to improve the affinity for the foam, it may cause stenosis. Therefore, it is preferable that the reinforcing yarn is composed only of glycolide- ⁇ -caprolactone copolymer without coating or the like.
- the glycolide: ⁇ -caprolactone ratio is preferably 90:10 to 45:55.
- the ratio of glycolide exceeds 90, the reinforcing yarn becomes hard and brittle, and the decomposition becomes too fast, which is not preferable for the regeneration of vascular tissue.
- the ratio of ⁇ -caprolactone exceeds 55, the reinforcing yarn becomes too soft and the effect of reinforcement becomes small, and the decomposition rate becomes slow, causing “calcification”.
- the positional relationship between the foam and the reinforcing material is such that the reinforcing material is located at the center or the outer surface of the tubular body that is the blood vessel regeneration substrate of the present invention, and the inner surface of the tubular body is the foam.
- the reinforcing material can sufficiently exert the role of maintaining the strength, and regeneration from the inside of the blood vessel can be promoted to perform early blood vessel regeneration.
- the reinforcing yarn is wound around the composite of the foam and the reinforcing material in a spiral shape, a ring shape, or an X shape. By arranging the reinforcing yarn in such a manner, the obtained blood vessel regeneration base material is more difficult to be crushed.
- the reinforcing yarn may be located at the center of the foam or at the outermost surface.
- the preferable lower limit of the winding pitch is 1 mm, and the preferable upper limit is 10 mm. If the winding pitch of the reinforcing yarn is less than 1 mm, it may cause "calcification" or cause delay in vascular regeneration. If it exceeds 10 mm, a sufficient reinforcing effect cannot be obtained. Sometimes. A more preferable lower limit of the winding pitch of the reinforcing yarn is 2 mm, and a more preferable upper limit is 8 mm.
- the preferable lower limit of the thickness of the vascular regeneration substrate according to the present invention is 0.3 mm, and the preferable upper limit is 1.5 mm. If the thickness of the blood vessel regeneration base material is less than 0.3 mm, sufficient strength that can withstand blood flow may not be obtained, or suturing may become difficult. The period may be longer and may cause calcification.
- the method for producing the blood vessel regeneration base material of the present invention is not particularly limited.
- a bioabsorbable material solution in which the previously prepared reinforcing material is placed in a mold and the foam is formed in the mold is used.
- a method of freeze-drying after pouring and then freeze-drying (freeze-drying method), adhering a mixed solution of a water-soluble substance and a bioabsorbable material forming the foam to the reinforcing material prepared in advance, and drying examples include a method (elution method) of washing out the water-soluble substance by washing with water.
- foams having various pore sizes can be prepared depending on the freezing temperature, the concentration of the polymer, and the like.
- the pore diameter of the foam can be controlled by adjusting the water-soluble substance particles.
- the blood vessel regeneration base material of the present invention is obtained by reinforcing a foam made of a bioabsorbable material against a force in the outward direction with a reinforcing material made of a bioabsorbable material, and further using a reinforcing yarn made of a bioabsorbable material.
- the foam becomes a scaffold to which cells can invade and adhere, and withstands blood flow for a period until the blood vessel regenerates after the reinforcing material and the reinforcing thread are transplanted. Plays a role in maintaining strength.
- the bioabsorbable material constituting the reinforcing yarn is a glycolide- ⁇ -caprolactone copolymer, it does not cause “calcification” due to rapid degradation.
- the blood vessel regeneration substrate of the present invention can regenerate blood vessels with extremely high efficiency by being transplanted into a blood vessel defect.
- the blood vessel regeneration substrate of the present invention may be transplanted as it is. Even when the vascular regeneration substrate of the present invention is transplanted as it is without seeding cells, the foam of the vascular regeneration substrate of the present invention becomes a good scaffold and cells easily invade to regenerate blood vessels. be able to.
- cells such as vascular endothelial cells, bone marrow cells, vascular smooth muscle cells, and fibroblasts are seeded in advance and then transplanted, blood vessel regeneration at an earlier stage can be expected.
- regeneration base material which can reproduce
- Example 1 A flat knitted fabric knitted into a cylindrical shape with 140 denier polyglycolide yarn was attached to a fluororesin rod having an outer diameter of 10 mm.
- a rod equipped with a flat knitted fabric was immersed in a 4% by weight dioxane solution of L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50), frozen at ⁇ 80 ° C., and then ⁇ 40 ° C. to 40 ° C.
- the foam was obtained by lyophilization at 12 ° C. for 12 hours. Next, it was removed from the fluororesin rod while being inverted, and mounted again on the fluororesin rod.
- a monofilament yarn (thickness 1-0) of glycolide- ⁇ -caprolactone copolymer (glycolide: ⁇ -caprolactone ratio (molar ratio) 75:25) as a reinforcing yarn is spiraled at a pitch of 3 mm. Wrapped in a shape.
- the foam wound with the monofilament yarn was immersed in a 4% by weight dioxane solution of L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50) for 30 seconds, frozen at ⁇ 80 ° C., and then ⁇ 40 Lyophilized at -40 ° C to 12 ° C for 12 hours.
- a vascular regeneration substrate having a sandwich structure having a foam layer having a thickness of 0.9 mm was obtained.
- Example 1 A vascular regeneration substrate was obtained in the same manner as in Example 1 except that a monofilament yarn (thickness 0.4 mm, USP size 1-0) of L-lactide- ⁇ -caprolactone copolymer was used as the reinforcing yarn. It was.
- a monofilament yarn (thickness 0.4 mm, USP size 1-0) of glycolide- ⁇ -caprolactone copolymer coated with L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50) is used.
- a blood vessel regeneration substrate was obtained in the same manner as in Example 1 except that. The coating was performed by dipping the monofilament yarn of glycolide- ⁇ -caprolactone copolymer in a 4% by weight dioxane solution of L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50) and then drying. went.
- the blood vessel regeneration base materials obtained in Examples, Comparative Examples and Reference Examples were evaluated by animal experiments by the following method.
- a part of the inferior vena cava of a beagle dog weighing approximately 10 kg was excised and replaced with the vascular regeneration substrate obtained in Examples, Comparative Examples, and Reference Examples.
- Tests were performed on 11 samples for Example 1, 4 samples for Comparative Example 1, and 8 samples for Reference Example 1, and the number of survivors was measured 6 months after the operation.
- Six months after the operation the blood vessel morphology was recorded by angiography, and then sacrificed, and the presence or absence of ascites was visually observed.
- transplanted part (regenerated blood vessel part) was touched with a finger to evaluate the presence or absence of sclerotic lesions and macroscopically the presence or absence of calcification. Furthermore, tissue sections were prepared, and histological evaluation was evaluated with a microscope, and the presence or absence of calcification was also evaluated with the Nishiyama method or the Von Kossa method. The results are shown in Table 2.
- Example 2 From Table 2, when the vascular regeneration base material of Example 1 and Comparative Example 1 was transplanted, the survival rate 6 months after the operation was 100%, and neither stenosis nor ascites was observed. However, calcification was not observed when the blood vessel regeneration base material of Example 1 was used, whereas when the blood vessel regeneration base material of Comparative Example 1 was used, lime that was evident in all specimens was observed.
- a tissue image of the transplanted part of the vascular regeneration substrate obtained in Comparative Example 1 was prepared, and a stained image stained by the Nishiyama method is shown in FIG. In Example 1, good patency of the blood vessel and histological creation of a tissue very similar to the venous blood vessel were observed, and no calcification was observed.
- FIG. 2 shows an incision image of the transplant site
- FIG. 3 shows a stained image of the transplant site when the vascular regeneration substrate of Example 1 was transplanted and sacrificed 13 months after the operation.
- the thickness of monofilament yarn of glycolide- ⁇ -caprolactone copolymer used as a reinforcing yarn is 1-0 (0.4 to 0.5 mm), 2-0 (0.35 to 0.4 mm), 3-0 ( A blood vessel regeneration base material was obtained in the same manner as in Example 1 except that the thickness was 0.25 to 0.3 mm), and the compression elasticity was evaluated. The results are shown in Table 3.
- regeneration base material which can reproduce
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
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Abstract
Description
本発明は、細胞の侵入のし易さと、つぶれにくさ、石灰化の防止を両立して、血管の欠損部に移植することにより、極めて高い効率で血管を再生することができる血管再生基材を提供することを目的とする。
以下に本発明を詳述する。
上記発泡体の孔径は、細胞が侵入し易く増殖し易いとともに、血管の欠損部に移植した際にほとんど血液漏れしない程度であることが必要であり、具体的には好ましい下限は5μm、好ましい上限は100μmである。上記発泡体の孔径が5μm未満であると、細胞が発泡体の孔内に侵入できないことがあり、100μmを超えると、移植したときに血液漏れを起こすことがある。上記発泡体の孔径のより好ましい下限は10μm、より好ましい上限は50μmである。
なお、上記発泡体の平均孔径は、例えば、水銀圧入法や画像解析法等の従来公知の方法により測定することができる。
上記親水化処理としては特に限定されず、例えば、プラズマ処理、グロー放電処理、コロナ放電処理、オゾン処理、表面グラフト処理又は紫外線照射処理等が挙げられる。なかでも、血管再生基材の外観を変化させることなく吸水率を飛躍的に向上できることからプラズマ処理が好適である。
上記補強材としては、上記発泡体より高強度であるものであれば特に限定されず、例えば、繊維状体、不織布状体又はフィルム状体等が挙げられる。なかでも、生体吸収性材料からなる繊維を編織成した横編地、縦編地、組紐、織地等の繊維状体が好適である。
上記補強糸は、モノフィラメント糸であってもよく、マルチフィラメント糸であってもよいが、より高い曲げ弾性を有し、圧迫力に耐えることができることから、モノフィラメント糸が好適である。
なお、原因は不明であるが、補強糸にコーティング等を施して上記発泡体に対する親和性を向上させると、かえって狭窄等の原因となることがある。従って、上記補強糸は、コーティング等を施さない、グリコリド-ε-カプロラクトン共重合体のみからなるものであることが好ましい。
上記補強糸は、このような上記発泡体と補強材との複合物に、スパイラル状、リング状又はX字状で巻回されている。このような態様にて補強糸が配置されることにより、得られる血管再生基材はよりつぶれにくいものとなる。上記補強糸は、発泡体の中心に位置しても、最外面に位置してもよい。
本発明に係る血管再生基材の厚みの好ましい下限は0.3mm、好ましい上限は1.5mmである。血管再生基材の厚みが0.3mm未満であると、血流に耐え得る充分な強度が得られなかったり、縫合が困難になったりすることがあり、1.5mmを超えると、吸収にかかる期間が徒に長くなり、石灰化の原因となることがある。
移植にあたっては、本発明の血管再生基材をそのまま移植してもよい。細胞を播種することなく本発明の血管再生基材をそのまま移植した場合であっても、本発明の血管再生基材の上記発泡体が良好な足場となり細胞が容易に侵入して血管を再生することができる。
また、予め血管内皮細胞、骨髄細胞、血管平滑筋細胞、線維芽細胞等の細胞を播種してから移植する場合には、より早期での血管再生を期待できる。
外径10mmのフッ素樹脂製の棒に140デニールのポリグリコリド糸にて筒状に編成した平編地を装着した。平編地を装着した棒を、L-ラクチド-ε-カプロラクトン共重合体(モル比50:50)の4重量%ジオキサン溶液中に浸漬し、-80℃で凍結した後、-40℃~40℃で12時間凍結乾燥して発泡体を得た。次いで、これを反転させながらフッ素樹脂製の棒から外し、再度、フッ素樹脂製の棒に装着した。発泡体の表面に、補強糸としてグリコリド-ε-カプロラクトン共重合体(グリコリド:ε-カプロラクトンの比率(モル比)が75:25)のモノフィラメント糸(太さ1-0)を3mmのピッチでスパイラル状に巻きつけた。モノフィラメント糸を巻きつけた発泡体を、L-ラクチド-ε-カプロラクトン共重合体(モル比50:50)の4重量%ジオキサン溶液中に30秒間浸漬し、-80℃で凍結した後、-40℃~40℃で12時間凍結乾燥した。このような方法により、0.9mmの厚さの発泡層を有するサンドイッチ構造の血管再生基材を得た。
補強糸として、L-ラクチド-ε-カプロラクトン共重合体のモノフィラメント糸(太さ0.4mm、USPサイズ1-0)を用いた以外は、実施例1と同様の方法により血管再生基材を得た。
補強糸として、L-ラクチド-ε-カプロラクトン共重合体(モル比50:50)でコーティングしたグリコリド-ε-カプロラクトン共重合体のモノフィラメント糸(太さ0.4mm、USPサイズ1-0)を用いた以外は実施例1と同様の方法により血管再生基材を得た。
なお、コーティングは、L-ラクチド-ε-カプロラクトン共重合体(モル比50:50)の4重量%ジオキサン溶液にグリコリド-ε-カプロラクトン共重合体のモノフィラメント糸を浸漬した後、乾燥させる方法にて行った。
得られたチューブ状の血管再生基材について、直径を1/2になるまで圧縮するときに必要な強度を求めた。この値が大きければ、狭窄に対し、高い口径維持力を有することを意味する。
また、直径を圧縮する方向に200gの力を繰り返し加え、横に潰れて形状が保てなくなるまでの回数を測定した。
結果を表1に示した。
実施例、比較例及び参考例で得られた血管再生基材について、以下の方法にて動物実験による評価を行った。
体重10Kg前後のビーグル犬の下大静脈を一部切除し、実施例、比較例及び参考例で得られた血管再生基材に置換した。実施例1については11検体、比較例1については4検体、参考例1については8検体の試験を行い、術後6ヵ月後の生存数を測定した。
術後6ヵ月後に血管造影検査にて血管の形態を記録し、その後犠牲死させ、腹水の有無を目視にて観察した。更に、移植部(再生血管部)を指で触り、硬化病変の有無、また、巨視的に石灰化の有無を評価した。更に、組織切片を作成し、組織学的評価を顕微鏡にて評価し、また西山法やVon Kossa法にて石灰化の有無も評価した。
結果を表2に示した。
実施例1の血管再生基材を移植し、術後13ヶ月後に犠牲死させたときの、移植部位の切開像を図2に、移植部位の染色像を図3に示した。
補強糸として用いる、グリコリド-ε-カプロラクトン共重合体のモノフィラメント糸の太さを1-0(0.4~0.5mm)、2-0(0.35~0.4mm)、3-0(0.25~0.3mm)とした以外は実施例1と同様の方法により血管再生基材を得て、圧縮弾性を評価した。
結果を表3に示した。
Claims (4)
- 生体吸収性材料からなる発泡体、前記発泡体を補強する生体吸収性材料からなる補強材、及び、前記発泡体を補強する生体吸収性材料からなる補強糸からなるチューブ状の血管再生基材であって、
前記補強糸と前記補強材とは、前記発泡体の中心又は外面に位置し、内面は前記発泡体であり、
前記補強糸は、スパイラル状、リング状又はX字状で巻回されており、かつ、
前記補強糸は、グリコリド-ε-カプロラクトン共重合体からなる
ことを特徴とする血管再生基材。 - 発泡体は、ラクチド(D、L、DL体)-ε-カプロラクトン共重合体からなることを特徴とする請求項1記載の血管再生基材。
- 補強糸は、スパイラル状で巻回されていることを特徴とする請求項1記載の血管再生基材。
- 補強糸と補強材とは、発泡体の中心に位置していることを特徴とする請求項1記載の血管再生基材。
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US13/056,239 US8496714B2 (en) | 2008-07-29 | 2009-07-28 | Base material for revascularization |
JP2010522728A JPWO2010013717A1 (ja) | 2008-07-29 | 2009-07-28 | 血管再生基材 |
EP09802960.6A EP2311506A4 (en) | 2008-07-29 | 2009-07-28 | BASIC MATERIAL FOR REVASCULARIZATION |
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JP2018089370A (ja) * | 2016-12-05 | 2018-06-14 | グンゼ株式会社 | 神経癒着防止ラッピング材 |
US10391068B2 (en) | 2012-08-06 | 2019-08-27 | Trustees Of Boston University | Prion protein ligands as therapeutic agents for neurodegenerative disorders |
JP7461133B2 (ja) | 2019-12-03 | 2024-04-03 | グンゼ株式会社 | 医療用充填基材 |
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JP2018089370A (ja) * | 2016-12-05 | 2018-06-14 | グンゼ株式会社 | 神経癒着防止ラッピング材 |
JP7461133B2 (ja) | 2019-12-03 | 2024-04-03 | グンゼ株式会社 | 医療用充填基材 |
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EP2311506A4 (en) | 2014-01-29 |
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