WO2017119474A1 - Substrat de régénération du ménisque - Google Patents

Substrat de régénération du ménisque Download PDF

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Publication number
WO2017119474A1
WO2017119474A1 PCT/JP2017/000233 JP2017000233W WO2017119474A1 WO 2017119474 A1 WO2017119474 A1 WO 2017119474A1 JP 2017000233 W JP2017000233 W JP 2017000233W WO 2017119474 A1 WO2017119474 A1 WO 2017119474A1
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layer
meniscus
cell
nonwoven fabric
regeneration
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PCT/JP2017/000233
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English (en)
Japanese (ja)
Inventor
周平 大槻
友彦 村上
悠紀 坂元
佐藤　秀樹
多恵 井上
Original Assignee
学校法人大阪医科薬科大学
グンゼ株式会社
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Application filed by 学校法人大阪医科薬科大学, グンゼ株式会社 filed Critical 学校法人大阪医科薬科大学
Priority to JP2017560425A priority Critical patent/JP6920691B2/ja
Publication of WO2017119474A1 publication Critical patent/WO2017119474A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/38—Joints for elbows or knees
    • 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

Definitions

  • the present invention relates to a meniscal regeneration base material capable of promoting the regeneration of the meniscus by filling the defect portion of the meniscus of the knee joint in the regeneration treatment of the meniscus.
  • FIG. 1 is a schematic cross-sectional view of the right knee joint taken along the sagittal plane
  • FIG. 2 is a schematic cross-sectional view of the right knee joint taken along the transverse plane.
  • the knee joint has a meniscus 1 between a femur 4 and a tibia 5, and cartilage 3 is formed on each side where the femur 4 and the tibia 5 face each other.
  • IPFP Infrapatella Fat Pad
  • the knee joint is wrapped with a joint capsule 7, and the inside of the joint is filled with joint fluid 8.
  • joint fluid 8 As shown in FIG. 2, a pair of meniscuses 1 are formed so as to oppose the inside and outside of the knee joint, and the front side and the back side of the knee joint are thick.
  • Meniscal degeneration or damage is one of the common conditions associated with cartilage degeneration in osteoarthritis (OA).
  • OA osteoarthritis
  • cartilage tissue is reduced and osteoarthritis of the knee progresses by excising the meniscus. Since the meniscus is a tissue containing many avascular regions, the self-regeneration ability is poor and self-repair is difficult. Therefore, in surgery, in order to promote meniscus healing, additional treatments such as growth factor, synovial transplantation, and bone marrow stimulation have been performed in addition to meniscus suture, but meniscus regeneration was insufficient. .
  • a regenerative medical base material for example, it has been proposed to use a nonwoven fabric made of a bioabsorbable material as disclosed in Patent Document 1.
  • a nonwoven fabric made of a bioabsorbable material is used as a base material for regenerative medicine or a suture reinforcing material, cells invade into the voids and proliferate, and the tissue is regenerated at an early stage.
  • tissue regeneration base material for example, it has been proposed to use such a tissue regeneration base material.
  • the present invention is a meniscal regeneration base material that can promote the regeneration of the meniscus by filling the defect portion of the meniscus of the knee joint in the regeneration treatment of the meniscus, and is made of a bioabsorbable material.
  • a film layer, a layer made of a nonwoven fabric having an average pore diameter of 5 to 20 ⁇ m made of a bioabsorbable material, and a layer made of a nonwoven fabric having an average pore diameter of 22 to 50 ⁇ m made of a bioabsorbable material are combined and integrated.
  • It is a meniscus recycled base material which consists of a laminated body whose surface is a film layer which consists of said bioabsorbable material. The present invention is described in detail below.
  • the present inventors examined the reason why regeneration is not sufficiently promoted when the meniscus is regenerated using a conventional tissue regeneration substrate.
  • the nonwoven fabric constituting the conventional tissue regeneration base material preferably has an average pore diameter of about 5 to 30 ⁇ m in order to ensure cell invasion.
  • the present inventor has found that such a conventional tissue regeneration substrate is superior in terms of cell invasiveness, but a part of the invaded cells pass through the tissue regeneration substrate, It has been found that leakage may occur outside the recycled substrate. Since the invading cells leaked out of the tissue regeneration substrate, the concentration of cell components that actually stayed in the affected area was insufficient, and it was considered that tissue regeneration was not promoted as expected.
  • a bioabsorbable material for a layer made of a nonwoven fabric having an average pore diameter of 22 to 50 ⁇ m (hereinafter also referred to as “cell invasion layer”) made of a bioabsorbable material.
  • cell invasion layer a layer made of a non-woven fabric having an average pore diameter of 5 to 20 ⁇ m
  • film layer made of a bioabsorbable material on at least one surface (hereinafter simply referred to as “film”).
  • the layer is also referred to as a “layer”
  • the layer is also referred to as a “layer”
  • the meniscal regeneration base material of the present invention comprises a laminate in which a film layer, a cell invasion layer, and a cell leakage prevention layer are combined and integrated.
  • the cell invasion layer serves as a scaffold for cell proliferation invading from surrounding tissues after transplantation and has a role of promoting meniscal regeneration.
  • the laminate may have only one cell invasion layer or two or more layers.
  • the cell invasion layer is made of a nonwoven fabric made of a bioabsorbable material.
  • the bioabsorbable material constituting the cell invasion layer include polyglycolide, polylactide, poly- ⁇ -caprolactone, lactide-glycolide copolymer, glycolide- ⁇ -caprolactone copolymer, and lactide- ⁇ -caprolactone copolymer.
  • Polymer polydioxanone, polycitric acid, polymalic acid, poly- ⁇ -cyanoacrylate, poly- ⁇ -hydroxy acid, polytrimethylene oxalate, polytetramethylene oxalate, polyorthoester, polyorthocarbonate, polyethylene carbonate, poly- ⁇ -Synthetic polymers such as benzyl-L-glutamate, poly- ⁇ -methyl-L-glutamate, poly-L-alanine, polysaccharides such as starch, alginic acid, hyaluronic acid, chitin, pectinic acid and their derivatives, gelatin , Collagen, al Min, natural polymers, and the like such as a protein of fibrin, and the like.
  • bioabsorbable materials may be used alone or in combination of two or more.
  • polyglycolide is preferable.
  • polyglycolide When polyglycolide is used, it is particularly excellent in cell invasiveness and normal tissue regeneration can be performed.
  • the period until the tensile strength becomes 1 ⁇ 2 before immersion is about 14 days.
  • the base material is gradually decomposed and absorbed when the cells proliferate and the tissue is regenerated, and a tissue regenerated to the inside of the base material is constructed. As a result, high quality regeneration is achieved.
  • An organization is considered to be built. Furthermore, since the inflammatory cells disappear within a few days after implantation in the living body, an excellent effect of hardly causing tissue adhesion can be exhibited.
  • polyglycolide means a polymer of glycolide such as polyglycolic acid, but other bioabsorbables such as lactide, ⁇ -caprolactone, p-dioxanone and the like within the range not inhibiting the effect of the present invention. It is good also as a copolymer with these components. Moreover, it is good also as a mixture with other bioabsorbable materials, such as a polylactide, in the range which does not inhibit the effect of this invention.
  • the preferred lower limit of the blended amount of the glycolide component in the copolymer is 60 mol%. .
  • the preferred lower limit of the blended amount of the glycolide component in the copolymer is 60 mol%. .
  • the preferred lower limit of the blending amount of polyglycolide in the mixture is 50 mol%.
  • the preferred lower limit of the weight average molecular weight of the polyglycolide is 30,000, and the preferred upper limit is 400,000. If the weight average molecular weight of the polyglycolide is less than 30000, the strength may be insufficient and a sufficient tissue reinforcing effect may not be obtained. If the weight average molecular weight exceeds 400000, the degradation rate in the living body becomes slow, causing a foreign body reaction. Sometimes.
  • the minimum with a more preferable weight average molecular weight of the said polyglycolide is 50000, and a more preferable upper limit is 300000.
  • a melt flow rate may be used as an alternative indicator of the molecular weight of the polyglycolide.
  • the preferable lower limit of the melt flow rate of the polyglycolide is 0.1 g / 10 minutes, and the preferable upper limit is 100 g / 10 minutes. Within this range, it becomes easy to produce a nonwoven fabric made of polyglycolide.
  • a more preferable lower limit of the melt flow rate of polyglycolide is 1 g / 10 minutes, and a more preferable upper limit is 50 g / 10 minutes.
  • the measurement condition of the melt flow rate means a value measured under the condition of a load of 4 kgf after the polyglycolide is melted while being held in a cylinder at 240 ° C. for 10 minutes.
  • the nonwoven fabric constituting the cell invasion layer has a lower limit of the average pore diameter of 22 ⁇ m and an upper limit of 50 ⁇ m.
  • a meniscal regeneration base material excellent in cell invasion and suitable for normal meniscal regeneration can be provided.
  • Cells can easily invade into pores having a pore diameter of 22 to 50 ⁇ m in the nonwoven fabric, and can grow and differentiate in the cell invasion layer to form a meniscal tissue.
  • the average pore diameter is less than 22 ⁇ m, the cells cannot efficiently enter, and if the average pore diameter exceeds 50 ⁇ m, the cells can enter but the distance between the cells is too large.
  • the cells adhering to the cell invasion layer and the cells invading from surrounding tissues cannot sufficiently proliferate and differentiate.
  • the preferable lower limit of the average pore diameter of the nonwoven fabric constituting the cell invasion layer is 24 ⁇ m
  • the preferable upper limit is 40 ⁇ m
  • the more preferable lower limit is 25 ⁇ m
  • the more preferable upper limit is 30 ⁇ m.
  • the average hole diameter of a nonwoven fabric means the average hole diameter measured by the bubble point method.
  • the bubble point method a liquid that wets the membrane to be measured well is absorbed in the pores of the membrane in advance and placed in an instrument as shown in FIG.
  • This is a method of measuring the minimum pressure (bubble point) at which bubbles can be observed on the surface and estimating the pore size distribution from the relational expression between the surface tension of the liquid and the bubble point (FIG. 4).
  • a wetting liquid for example, a fluorinated solvent, trade name Porofil (trademark)
  • FIG. 3 for example, Porometer manufactured by Nippon Bell Co., Ltd.
  • ⁇ represents the surface tension of the infiltrating liquid
  • ⁇ represents the contact angle of the infiltrating liquid on the nonwoven fabric material
  • ⁇ P represents the bubble point pressure
  • the average fiber diameter of the nonwoven fabric which comprises the said cell penetration layer is not specifically limited, A preferable minimum is 10 micrometers and a preferable upper limit is 50 micrometers. When the average fiber diameter of the nonwoven fabric is in this range, it becomes easy to adjust the average pore diameter to the specified range.
  • the minimum with a more preferable average fiber diameter of the said nonwoven fabric is 15 micrometers, and a more preferable upper limit is 40 micrometers.
  • the thickness of the said cell penetration layer is not specifically limited, A preferable minimum is 100 micrometers and a preferable upper limit is 3 mm.
  • a preferable minimum is 100 micrometers and a preferable upper limit is 3 mm.
  • the thickness of the cell invasion layer is less than 100 ⁇ m, a meniscus having a sufficient thickness may not be regenerated, and when it exceeds 3 mm, the handling property may be inferior.
  • the more preferable lower limit of the thickness of the cell invasion layer is 150 ⁇ m, and the more preferable upper limit is 2.5 mm.
  • the cell leakage prevention layer has a role of preventing invaded cells from leaking out of the meniscus regeneration substrate.
  • cells that proliferate in the cell invasion layer also enter the cell leakage prevention layer, forming a dense tissue between cells, promoting proliferation and differentiation, and promoting the regeneration of more normal meniscal tissue It also has a role to play.
  • the laminate may have only one cell leakage prevention layer or two or more layers.
  • the cell leakage prevention layer is made of a nonwoven fabric made of a bioabsorbable material.
  • the bioabsorbable material constituting the cell leakage prevention layer the same bioabsorbable material as that used for the cell invasion layer can be used.
  • the bioabsorbable material constituting the cell leakage prevention layer may be the same as or different from the bioabsorbable material constituting the cell invasion layer.
  • the nonwoven fabric constituting the cell leakage prevention layer has a lower limit of the average pore diameter of 5 ⁇ m and an upper limit of 20 ⁇ m.
  • the cell leakage prevention layer satisfies such an average pore size, it is possible to prevent the leakage of cells, and the cells grown in the cell invasion layer can also enter the cell leakage prevention layer. Can form a dense structure.
  • the average pore diameter of the nonwoven fabric constituting the cell leakage prevention layer exceeds 20 ⁇ m, leakage of cells from the meniscal regeneration substrate cannot be sufficiently prevented.
  • the average pore diameter of the nonwoven fabric constituting the cell leakage prevention layer is less than 5 ⁇ m, the invasion of cells into the cell leakage prevention layer may be lowered, and the regeneration of the meniscal tissue may not be sufficiently promoted.
  • the preferable lower limit of the average pore diameter of the nonwoven fabric constituting the cell leakage prevention layer is 6 ⁇ m, the preferable upper limit is 18 ⁇ m, the more preferable lower limit is 7 ⁇ m, and the more preferable upper limit is 16 ⁇ m.
  • the average fiber diameter of the nonwoven fabric which comprises the said cell leakage prevention layer is not specifically limited, A preferable minimum is 0.7 micrometer and a preferable upper limit is 7.0 micrometers. When the average fiber diameter of the nonwoven fabric is in this range, it becomes easy to adjust the average pore diameter to the specified range.
  • the minimum with a more preferable average fiber diameter of the said nonwoven fabric is 0.9 micrometer, and a more preferable upper limit is 5.0 micrometers.
  • the thickness of the cell leakage preventing layer is not particularly limited, but a preferable lower limit is 10 ⁇ m and a preferable upper limit is 150 ⁇ m. If the thickness of the cell leakage prevention layer is less than 10 ⁇ m, leakage of cells from the meniscal regeneration substrate may not be sufficiently prevented. If the thickness exceeds 150 ⁇ m, the area into which cells cannot enter increases and normal Meniscus tissue may not be regenerated. A more preferable lower limit of the thickness of the cell leakage preventing layer is 30 ⁇ m, and a more preferable upper limit is 100 ⁇ m.
  • the film layer is disposed on at least one surface of the laminate, and further prevents cells that have entered the meniscal regeneration substrate of the present invention from leaking and improves slipperiness. Thus, it has a role of preventing the surface of the base material from being worn by friction due to contact with the cartilage after transplantation.
  • the film layer may be disposed on at least one surface of the laminate, but is preferably disposed on both surfaces.
  • the film means a thin film-like body that does not have at least a ⁇ m-order hole that can be observed with an optical microscope.
  • the same bioabsorbable material as that used for the cell invasion layer and the cell leakage prevention layer can be used.
  • the bioabsorbable material constituting the film layer may be the same as or different from the bioabsorbable material constituting the cell invasion layer or the cell leakage preventing layer.
  • lactide- ⁇ -caprolactone copolymer is preferable because it can exhibit high wear resistance.
  • the film layer may contain a lubricant for the purpose of further improving the slipperiness as long as the medical use is not impaired.
  • the thickness of the said film layer is not specifically limited, A preferable minimum is 10 micrometers and a preferable upper limit is 500 micrometers. If the thickness of the film layer is less than 10 ⁇ m, it may not be possible to sufficiently prevent the surface of the base material from being worn by friction due to contact with cartilage after transplantation. May be inferior. The more preferable lower limit of the thickness of the film layer is 25 ⁇ m, and the more preferable upper limit is 250 ⁇ m.
  • the film layer, the cell leakage prevention layer, and the cell invasion layer are combined and integrated. If the above layers are not combined and integrated, when transplanting the meniscal recycled substrate of the present invention, some or all of the above layers may be peeled off. If even a part of each of the above-mentioned layers is peeled off, cell accumulation may occur in the space formed in the peeled portion, and normal tissues or organs may not be regenerated.
  • the above-mentioned layers are combined and integrated means that the layers are not peeled even when folded and transplanted when transplanting the meniscal recycled substrate of the present invention. More quantitatively, the peel strength measured according to the peel strength test method specified in JIS L 1021-9 is preferably 0.1 N or more, and more preferably 0.3 N or more. .
  • the film layer, the cell leakage prevention layer, and the cell invasion layer are combined and integrated, and at least one surface may be the film layer, and each layer may have a plurality of layers.
  • a five-layer structure of film layer / cell invasion layer / cell leakage prevention layer / cell invasion layer / film layer, film layer / cell invasion layer / film layer / cell leakage prevention layer / film layer / cell invasion A 10-layer structure of layer / film layer / cell leakage prevention layer / film layer / cell invasion layer may be used.
  • FIG. 5 The schematic diagram which shows an example of the meniscus reproduction
  • the film layer 11, the cell leakage prevention layer 12, the cell invasion layer 13, and the film layer 11 are laminated and integrated in this order.
  • the film layer 21, the cell intrusion layer 23, the cell leakage prevention layer 22, the cell intrusion layer 23, and the film layer 21 are laminated and integrated in this order.
  • the method for producing the meniscal recycled substrate of the present invention is not particularly limited.
  • the cell leakage prevention layer and the cell invasion layer are separately prepared, they are bonded using a medical adhesive.
  • a method in which a part of the surface of each layer is dissolved with a solvent and then bonded are bonded.
  • the cell leakage preventing layer is formed on the cell invasion layer by discharging a yarn made of a bioabsorbable material by a melt blow method,
  • the cell invasion layer is prepared.
  • the method for preparing the cell invasion layer is not particularly limited. For example, electrospinning deposition method, melt blow method, needle punch method, spun bond method, flash spinning method, hydroentanglement method, airlaid method, thermal bond method, resin bond A conventionally known method such as a method or a wet method can be used.
  • the needle punch method is suitable for the preparation of the cell invasion layer.
  • a feathering treatment may be applied to the surface of the cell invasion layer on the side where the cell leakage prevention layer is laminated.
  • a feathering treatment By performing a feathering treatment on the surface of the cell intrusion layer in advance, the adhesion with the cell leakage preventing layer is further improved.
  • Specific examples of the feathering treatment include a method of raising the surface of the cell entry layer on the side where the cell leakage prevention layer is laminated using a raising machine.
  • the needle punch method is used as the method for producing the cell invasion layer, the surface of the obtained cell invasion layer is already raised, so that the same effect as that obtained by performing the feathering treatment is obtained. It is done.
  • the cell leakage prevention layer is then formed on the cell intrusion layer by discharging a yarn made of a bioabsorbable material by a melt blow method.
  • the melt blow method is a melt spinning method in which a bioabsorbable material as a raw material is made into a nonwoven fabric in one stage. Specifically, the bioabsorbable material melted by the extruder was blown out into a fiber shape from a die having a large number of die in the width direction toward the fiber collecting point at a high temperature and high speed air flow, and stretched into a fiber shape. The resin is accumulated on a conveyor. A nonwoven fabric is formed because entanglement and fusion of fibers occur during ejection and accumulation.
  • the cell intrusion layer is disposed on the conveyor so as to be in front of the fiber collection point by the melt blow method, and the fibers are discharged onto the cell intrusion layer while moving the cell intrusion layer on the conveyor.
  • a cell leakage prevention layer is formed.
  • the fiber diameter, density, thickness and the like of the formed cell leakage prevention layer can be controlled by adjusting the polymer discharge amount of the melt blow method, the air wind speed near the discharge outlet, the speed of the conveyor, and the like.
  • needle punching is performed so that the needle enters from the cell leakage prevention layer side of the obtained laminate of the cell entry layer and the cell leakage prevention layer, and the cell entry layer and the cell Combine the leakage prevention layer with the composite.
  • the needle punch the cell invasion layer and the cell leakage prevention layer can be reliably combined and integrated without blocking the holes of the respective layers on the joint surface.
  • the film layer is then laminated on one or both surfaces of the obtained laminate of the cell intrusion layer and the cell leakage prevention layer.
  • a method of laminating the film layer for example, a method of applying a solvent capable of dissolving the film layer to the surface of the film layer and dissolving a part thereof, and then bonding the film layer to one or both surfaces of the laminate Etc.
  • regeneration of a meniscus can be provided by filling the defect
  • Example 1 Preparation of nonwoven fabric for cell invasion layer A polyglycolide having a weight average molecular weight of 250,000 is used as a bioabsorbable material, and a fabric made of yarn obtained by spinning the same is made into a nonwoven fabric by a needle punch method. A nonwoven fabric for cell invasion layer having a diameter of about 20 ⁇ m and a thickness of about 300 ⁇ m was obtained.
  • the moving speed of the conveyor was set to a speed at which the density of the nonwoven fabric obtained by the melt blowing method was 10 g / m 2 .
  • the nonwoven fabric which consists only of a cell leakage prevention layer on the same conditions separately was manufactured and the average hole diameter of the nonwoven fabric was computed by the bubble point method, it was 12 micrometers.
  • L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50, weight average molecular weight 200,000) was dissolved in dioxane to prepare a 4 wt% dioxane solution.
  • the obtained solution was poured into a glass petri dish, air-dried and heat-treated to obtain a film having a thickness of about 100 ⁇ m.
  • a small amount of dioxane is applied to the surface of one side of the obtained film to partially dissolve it, and the resulting nonwoven fabric for cell intrusion layer is laminated and dried to combine the film and the nonwoven fabric. To obtain a meniscus recycled substrate.
  • Example 2 A Teflon (registered trademark) sheet was placed on the conveyor so as to be in front of the fiber collection point by the melt blow method. While moving the conveyor, a polyglycolide yarn was discharged onto a Teflon (registered trademark) sheet by a melt blow method to obtain a cell leakage prevention layer having an average fiber diameter of about 1 ⁇ m and a thickness of about 380 ⁇ m.
  • the melt blow method was performed using polyglycolide having a weight average molecular weight of 250,000 as a raw material, a polymer discharge rate of 0.2 kg / h, and an air wind speed of 11 m / sec near the discharge outlet.
  • the moving speed of the conveyor was set to a speed at which the density of the nonwoven fabric obtained by the melt blowing method was 10 g / m 2 .
  • the obtained nonwoven fabric for cell leakage prevention layers it was 12 micrometers when the average hole diameter of the nonwoven fabric was computed by the bubble point method.
  • L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50, weight average molecular weight 200,000) was dissolved in dioxane to prepare a 4 wt% dioxane solution.
  • the obtained solution was poured into a glass petri dish, air-dried and heat-treated to obtain a film having a thickness of about 100 ⁇ m.
  • a small amount of dioxane is applied to the surface of one side of the obtained film to partially dissolve it, and the resulting non-woven cell leakage prevention layer is laminated and dried to combine the film and the non-woven fabric. To obtain a meniscus recycled substrate.
  • a rabbit was prepared as an experimental animal, and the anterior segment to middle segment (portion surrounded by a dotted line in FIG. 2) of the medial meniscus of the right knee joint was excised.
  • the meniscus regenerated substrate obtained in the examples and comparative examples was transplanted and sutured to the meniscus removal part. Sacrificing 8 weeks after the operation and observing the right knee joint, in Example 1, it was confirmed that the meniscus-like tissue was regenerated to the extent that the removed portion was completely filled. On the other hand, in Comparative Examples 1 to 3, regeneration of the meniscus-like tissue was not observed.
  • Example 2 Preparation of nonwoven fabric for cell invasion layer A polyglycolide having a weight average molecular weight of 250,000 is used as a bioabsorbable material, and a fabric made of yarn obtained by spinning the same is made into a nonwoven fabric by a needle punch method. A nonwoven fabric for cell invasion layer having a diameter of about 20 ⁇ m and a thickness of about 300 ⁇ m was obtained.
  • L-lactide- ⁇ -caprolactone copolymer (molar ratio 50:50, weight average molecular weight 200,000) was dissolved in dioxane to prepare a 4 wt% dioxane solution. The obtained solution was poured into a glass petri dish, air-dried and heat-treated to obtain a film for a film layer having a thickness of about 100 ⁇ m.
  • nonwoven fabric for cell leakage prevention layer Polyglycolide was used as a bioabsorbable material, and a nonwoven fabric was produced by a melt blow method using a general-purpose small extruder having a screw diameter of 20 mm. The inside of the hopper was purged with nitrogen gas, spinning was performed under hot air, and the nonwoven fabric for cell leakage prevention layer having an average fiber diameter of about 1 ⁇ m and a thickness of about 80 ⁇ m was obtained by adjusting the discharge amount and the speed of the belt conveyor. .
  • the melt blow method was performed using polyglycolide having a weight average molecular weight of 250,000 as a raw material, a polymer discharge rate of 0.2 kg / h, and an air wind speed of 11 m / sec near the discharge outlet. Moreover, the moving speed of the conveyor was set to a speed at which the density of the nonwoven fabric obtained by the melt blowing method was 10 g / m 2 . In addition, when the nonwoven fabric which consists only of a cell leakage prevention layer on the same conditions separately was manufactured and the average hole diameter of the nonwoven fabric was computed by the bubble point method, it was 12 micrometers.
  • a rabbit was prepared as an experimental animal, and a part of the anterior to middle segment (portion surrounded by a dotted line in FIG. 2) of the medial meniscus of the right knee joint was excised.
  • the meniscus regeneration base material obtained in Example 2 was transplanted and sutured to the meniscus removal part. Further, as a comparison object, an experiment in which a meniscus regenerating substrate was sutured without being transplanted to a meniscus removing portion, and an experiment in which a scalpel was inserted and closed without removing the meniscus as a sham control were also performed.
  • FIG. 6 shows a photomicrograph image of the obtained specimen stained with safranin O. From FIG. 6, 12 weeks after the operation, regeneration of the cartilage tissue similar to that of the sham control (a portion stained red in the stained image) was observed in the portion transplanted with the meniscal regeneration base material.
  • regeneration of a meniscus can be provided by filling the defect

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Abstract

L'objet de la présente invention est de pourvoir à un substrat de régénération du ménisque qui, par comblement de la partie défectueuse du ménisque du genou, peut favoriser la régénération du ménisque dans le cadre d'une thérapie régénératrice du ménisque. La présente invention concerne un substrat de régénération du ménisque qui, par comblement de la partie défectueuse du ménisque du genou, peut favoriser la régénération du ménisque dans le cadre d'une thérapie régénératrice du ménisque, le substrat de régénération du ménisque comprenant un stratifié caractérisé en ce qu'une couche formant film constituée d'un matériau bioabsorbable, une couche constituée d'un tissu non tissé qui est à base d'un matériau bioabsorbable et a un diamètre de pore moyen de 5 à 20 µm, et une couche constituée d'un tissu non tissé qui est à base d'un matériau bioabsorbable et a un diamètre moyen de pore de 22 à 50 µm, sont combinées pour former un tout, une surface au moins du stratifié étant la couche formant film constituée du matériau bioabsorbable.
PCT/JP2017/000233 2016-01-08 2017-01-06 Substrat de régénération du ménisque WO2017119474A1 (fr)

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Application Number Priority Date Filing Date Title
JP2017560425A JP6920691B2 (ja) 2016-01-08 2017-01-06 半月板再生基材

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016-002732 2016-01-08
JP2016002732 2016-01-08

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