WO2017010299A1 - Procédé pour produire un modèle vasculaire d'un organisme et procédé pour produire un modèle d'un organe d'un organisme - Google Patents

Procédé pour produire un modèle vasculaire d'un organisme et procédé pour produire un modèle d'un organe d'un organisme Download PDF

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Publication number
WO2017010299A1
WO2017010299A1 PCT/JP2016/069403 JP2016069403W WO2017010299A1 WO 2017010299 A1 WO2017010299 A1 WO 2017010299A1 JP 2016069403 W JP2016069403 W JP 2016069403W WO 2017010299 A1 WO2017010299 A1 WO 2017010299A1
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Prior art keywords
model
biological
biological tube
male mold
water
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PCT/JP2016/069403
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English (en)
Japanese (ja)
Inventor
裕久 外園
岩戸　薫
若田　裕一
潤 桝本
早 大住
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富士フイルム株式会社
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Priority to JP2017528376A priority Critical patent/JP6621824B2/ja
Publication of WO2017010299A1 publication Critical patent/WO2017010299A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09B—EDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28—Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine

Definitions

  • the present invention relates to a method for manufacturing a biological tube model and a method for manufacturing a biological organ model.
  • Patent Document 1 includes “an aqueous gel composed of polyvinyl alcohol having an average polymerization degree of 300 to 3500 and a saponification degree of 90 mol% or more, and silica particles.
  • a molding material for organ model is disclosed.
  • an object of the present invention is to provide a method of manufacturing a biological tube model from which a biological tube model can be easily obtained, and a method of manufacturing a biological organ model using the biological tube model obtained by the above method.
  • the present invention provides the following [1] to [6].
  • [1] A male composition having a shape corresponding to the shape of a biological tube is brought into contact with a precursor composition containing a water-soluble polymer and water, and the male mold is formed by a gel film containing the water-soluble polymer and water.
  • a method of manufacturing a biological tube model comprising: a step of covering the surface of the tube; and a step of releasing the male mold from the gel film to obtain a hollow biological tube model made of the gel film.
  • the step of coating the surface of the male mold with the gel coating is a step of depositing the gel coating on the surface of the male mold by immersing the male mold cooled in advance in the precursor composition.
  • a biological tube model obtained by the method for manufacturing a biological tube model according to any one of [1] to [5] is disposed in a female internal space having an inner surface shape corresponding to the shape of a biological organ. Injecting a precursor composition containing a water-soluble polymer and water into the internal space to produce a gel body containing the water-soluble polymer and water, and separating the female mold from the gel body. And obtaining a living organ model made of the gel body containing a part or all of the living body tube model.
  • the present invention it is possible to provide a method of manufacturing a biological tube model in which a biological tube model can be easily obtained, and a method of manufacturing a biological organ model using the biological tube model obtained by the above method.
  • FIG. 1A is a cross-sectional view showing an example of a preferred embodiment of the method for producing a biological tube model of the present invention, showing a state in which a male mold and a precursor composition are prepared.
  • FIG. 1B is a cross-sectional view showing an example of a preferred embodiment of the method for producing a biological tube model of the present invention, and shows a state in which a precursor composition is brought into contact with a male mold.
  • FIG. 1C is a cross-sectional view showing an example of a preferred embodiment of the method for manufacturing a biological tube model of the present invention, and shows a state in which a male surface is covered with a gel film.
  • FIG. 1A is a cross-sectional view showing an example of a preferred embodiment of the method for producing a biological tube model of the present invention, showing a state in which a male mold and a precursor composition are prepared.
  • FIG. 1B is a cross-sectional view showing an example of a preferred embodiment of the method for producing a biological tube model
  • FIG. 1D is a cross-sectional view showing an example of a preferred embodiment of the method for manufacturing a biological tube model of the present invention, and shows a state where the male mold is released from the gel film.
  • FIG. 2 is a cross-sectional view showing an example of a preferred embodiment of a biological tube model into which a simulated body fluid has been injected.
  • FIG. 3A is a cross-sectional view showing an example of a preferred embodiment of the method for manufacturing a biological organ model of the present invention, and shows a state in which the biological tube model is arranged in a female internal space.
  • FIG. 3B is a cross-sectional view showing an example of a preferred embodiment of the method for producing a living organ model of the present invention, and shows a state in which a precursor composition is injected into the female internal space.
  • FIG. 3C is a cross-sectional view showing an example of a preferred embodiment of the method for producing a living organ model of the present invention, and shows a state where the female mold is released from the gel body.
  • a numerical range expressed using “ ⁇ ” in this specification means a range including numerical values described before and after “ ⁇ ” as a lower limit value and an upper limit value.
  • a water-soluble polymer and water are brought into contact with a male composition surface having a shape corresponding to the shape of the biological tube by bringing a precursor composition containing the water-soluble polymer and water into contact therewith.
  • FIGS. 1A to 1D and FIG. 1A to 1D are cross-sectional views showing an example of a preferred embodiment of the method for manufacturing a biological tube model of the present invention.
  • 1A shows a state in which a male mold and a precursor composition are prepared
  • FIG. 1B shows a state in which the precursor composition is brought into contact with the male mold
  • FIG. 1C shows that the surface of the male mold is coated with a gel film
  • FIG. 1D shows a state in which the male mold is released from the gel film.
  • a male mold 11 is prepared.
  • the male mold 11 is a mold (core) for obtaining a biological tube model simulating a biological tube.
  • the biological duct is not particularly limited as long as it is an organ having a tubular structure in a living body, and examples thereof include a bile duct and a ureter in addition to blood vessels such as veins, arteries, and portal veins.
  • FIG. 1A shows a male mold 11 having a shape corresponding to a dendritic hepatic vein form as an example.
  • the material of the male mold 11 is not particularly limited, but for reasons described later, a material having flexibility such as a soft rubbery polymer substance is preferable.
  • the manufacturing method of the male mold 11 is not particularly limited, but it is preferable to manufacture the male mold 11 using a 3D (three-dimensional) printer because a shape conforming to the actual product can be obtained.
  • the 3D printer uses 3D data of a biological tube such as a blood vessel. At this time, a more precise biological tube model can be obtained by using patient-specific data (after being appropriately processed).
  • the precursor composition 21 is also prepared.
  • the precursor composition 21 contains at least a water-soluble polymer and water.
  • the water-soluble polymer include polyvinyl alcohol (PVA).
  • PVA polyvinyl alcohol
  • Polyvinyl alcohol (PVA) is generally obtained by saponifying polyvinyl acetate obtained by polymerizing vinyl acetate monomers. It does not specifically limit as polyvinyl alcohol used for this invention, A conventionally well-known polyvinyl alcohol can be used suitably.
  • the average degree of polymerization (viscosity average degree of polymerization) determined by the viscosity method of polyvinyl alcohol is preferably 300 to 3,500, more preferably 500 to 3000, and even more preferably 1000 to 2500.
  • the saponification degree of polyvinyl alcohol is preferably 90 mol% or more, more preferably 95 mol% or more, and still more preferably 98 mol% or more.
  • the upper limit of the saponification degree is not limited, and it is preferably as high as possible. Particularly preferred is completely saponified polyvinyl alcohol.
  • Polyvinyl alcohol may be used alone or in combination of two or more.
  • the concentration of the water-soluble polymer such as polyvinyl alcohol is, for example, 4 to 20% by mass with respect to the total mass of the precursor composition 21, preferably 5 to 20% by mass, and more preferably 5 to 15% by mass. preferable.
  • the precursor composition 21 may contain an arbitrary additive as necessary.
  • the precursor composition 21 is brought into contact with the surface of the male mold 11.
  • the precursor composition 21 is a brush
  • the gel film 22 is a film obtained by gelling the precursor composition 21.
  • the gel film 22 contains at least a water-soluble polymer and water, like the precursor composition 21.
  • a mode in which the gel film 22 is deposited on the surface of the male mold 11 by immersing the male mold 11 cooled in advance in the precursor composition 21 is preferable. More specifically, for example, first, the male mold 11 is previously cooled to, for example, about ⁇ 10 ° C. or less, and the precursor composition 21 is a PVA aqueous solution containing polyvinyl alcohol and water as described above. Is prepared (see FIG. 1A). Next, the cooled male mold 11 is immersed in the precursor composition 21 that is an aqueous PVA solution for about 10 to 60 seconds (see FIG. 1B). Then, the precursor composition 21 near the surface of the male mold 11 is cooled, frozen, and gelled.
  • the gel film 22 is formed on the surface of the male mold 11 by pulling up the male mold 11 from the precursor composition 21 and thawing (see FIG. 1C).
  • the gel film 22 can be formed uniformly on the surface of the male mold 11 in a short time. Therefore, it is preferable.
  • the male mold 11 has a complicated shape such as a dendritic shape, it is easy to generate unpainted parts and the like when the precursor composition 21 is applied by brush coating or the like. On the surface, it is difficult for unpainted parts to occur, and it can be applied uniformly and in a short time.
  • the gel film 22 is formed simply by immersing and pulling up the cooled male mold 11, the gel film 22 can be easily formed into a uniform film thickness without complicated processes such as heat treatment. Can be formed in a short time.
  • the precursor composition 21 you may use the aqueous solution which contains a borate ion further besides polyvinyl alcohol and water.
  • the gel film 22 is formed by bringing the aqueous solution into contact with the surface of the male mold 11 without cooling the male mold 11 in advance, and then performing an effect treatment such as heating.
  • the male mold 11 is released (desorbed) from the gel film 22 to obtain a hollow biological tube model 31 made of the gel film 22.
  • a blood vessel model simulating the hepatic vein is obtained as the biological tube model 31.
  • the method for releasing the male mold 11 is not particularly limited.
  • a through-hole 33 in which the gel film 22 is not closed is formed on the surface of the male mold 11, and the process shown in FIG. 1D is performed.
  • a method of pulling out the male mold 11 from the through-hole 33 can be mentioned.
  • the male mold 11 can be easily detached from the gel film 22.
  • the male mold 11 is preferably made of a soft material having flexibility. If the male mold 11 having flexibility is used, the gel film 22 is easily deformed along the shape of the gel film 22 when pulled out from the gel film 22, and the gel film 22 is hardly damaged.
  • “having flexibility” means deformation without being broken or damaged when an external force such as pushing, bending, or twisting is applied.
  • FIG. 2 is a cross-sectional view showing an example of a preferred embodiment of a biological tube model into which a simulated body fluid has been injected.
  • the hollow biological tube model 31 (see FIG. 1D) may be used as it is.
  • a simulated body fluid 32 simulating body fluid is injected into the biological tube model 31 from, for example, the through-hole 33. May be.
  • the biological tube model 31 becomes a more realistic model.
  • Examples of the simulated body fluid 32 include simulated blood that simulates blood.
  • the biological tube model 31 is included in a biological organ model formed using a female mold.
  • the biological tube model 31 in a state where the simulated body fluid 32 that is a liquid is injected may be inferior in handling property when placed in the female internal space.
  • the hole 33 is sealed and the shape is appropriately adjusted, it is used in a cooled and solidified state.
  • the hollow body model 31 in which the simulated body fluid 32 is not injected may be cooled and solidified.
  • the biological organ model manufacturing method of the present invention includes a step of arranging the biological tube model obtained by the biological tube model manufacturing method of the present invention in a female internal space having an inner surface shape corresponding to the form of the biological organ. A step of injecting a water-soluble polymer and water-containing precursor composition into the internal space to form a water-soluble polymer and water-containing gel body, and releasing the female mold from the gel body. And a step of obtaining a living organ model composed of the gel body containing part or all of the living body tube model. Since the biological organ model obtained in this way includes the biological tube model, it is possible to perform surgical training or the like that is more realistic.
  • FIGS. 3A to 3C are cross-sectional views showing an example of a preferred embodiment of the method for manufacturing a biological organ model of the present invention.
  • FIG. 3A shows a state in which the biological tube model is disposed in the female internal space
  • FIG. 3B shows a state in which the precursor composition is injected into the female internal space
  • the biological tube model 31 is placed in the internal space 52 formed by the female mold 51.
  • the female mold 51 is a mold for obtaining a living organ model imitating a living organ such as a liver, and is made of, for example, a hard material.
  • the female mold 51 is also preferably manufactured using a 3D (three-dimensional) printer for the same reason as the male mold 11.
  • a female mold 51 having an inner surface shape corresponding to the form of the liver is shown. That is, the internal space 52 imitating the shape of the liver is formed by the inner surface shape of the female mold 51.
  • the female mold 51 is formed with an injection hole 53 through which the precursor composition 41 (see FIG. 3B) is injected into the internal space 52.
  • the biological tube model 31 is disposed in the internal space 52 in a state of being cooled and solidified as described above.
  • the precursor composition 41 is injected from the injection hole 53 to fill the internal space 52, and a gel body 42 (see FIG. 3C) reflecting the shape of the internal space 52 is generated. .
  • the precursor composition 41 the same composition as the precursor composition 21 described above (an aqueous solution containing PVA as a water-soluble polymer) can be suitably used.
  • the precursor composition 41 preferably contains gelatin.
  • the concentration of gelatin is preferably 0.1 to 8.0% by mass and more preferably 0.3 to 5.0% by mass with respect to the total mass of the precursor composition 41.
  • the precursor composition 41 preferably contains an electrolyte such as sodium chloride.
  • the concentration of the electrolyte is preferably 0.15 to 2.00% by mass and more preferably 0.15 to 1.90% by mass with respect to the total mass of the precursor composition 41.
  • the precursor composition 41 may contain an arbitrary additive as necessary.
  • the gel body 42 is a gel body in which the precursor composition 41 is gelled. For this reason, the gel body 42 contains at least a water-soluble polymer and water, like the precursor composition 41. Although it does not specifically limit as a method of producing
  • PVA polyvinyl alcohol
  • the gel 51 is obtained by cooling the female mold 51 in a state of being injected at, for example, about ⁇ 10 ° C. or less for about 1 to 10 hours and then thawing. The PVA aqueous solution is frozen by the cooling, but at this time, it gels.
  • the female mold 51 is released from the gel body 42.
  • the female mold 51 is configured to be divided as an example.
  • a living organ model 61 including a gel body 42 including the living tube model 31 can be taken out.
  • the simulated body fluid 32 injected into the biological tube model 31 may be liquefied.
  • the through-hole 33 (see FIG. 2 and the like) of the biological tube model 31 is also present. If covered with the gel body 42, the simulated body fluid 32 is prevented from leaking from the living organ model 61.
  • a surface thin film that looks like a sputum, a sputum, or a blood vessel may be formed as necessary.
  • the biological organ model 61 obtained in this way contains the biological tube model 31 that imitates a biological tube, it is more practical as a biological organ model for practicing surgical techniques. At this time, if a biological tube model imitating a patient-specific biological tube is used as the biological tube model 31, very precise surgical training, a pre-operative conference, and the like are possible.
  • liver model resembling a human liver has been mainly described as an example, but the present invention is not limited to this, and other biological organs include, for example, the brain, heart, esophagus, stomach , Bladder, small intestine, large intestine, kidney, pancreas, spleen, uterus and the like.
  • liver blood vessels hepatic vein, hepatic artery and portal vein
  • 3D printer trade name: Object 260 Connex, manufactured by Stratasys
  • Liver blood vessel 3D data used in the 3D printer was obtained by processing on a computer 3D data of a certain individual obtained from a 3D image analysis system (trade name: Volume Analyzer SYNAPSE VNCENT, manufactured by FUJIFILM Corporation).
  • 3D graphic software manufactured by E Frontier, trade name: Shade 3D
  • Rubber-like TangoPlus manufactured by Stratasys was used as the ink for the 3D printer, which is a male material.
  • the male mold coated with the gel film is left at room temperature (25 ° C.).
  • the gel film becomes soft and stretchable, the rubber-like male mold is pulled out to obtain a hollow blood vessel model composed of the gel film. It was.
  • a blood vessel model simulating the hepatic vein, hepatic artery and portal vein was prepared.
  • a bile duct model was prepared in the same manner as the blood vessel model.
  • the bile duct model was solidified with ice in the same manner as the vascular model.
  • a female mold having an inner surface shape corresponding to the shape of the human liver was produced using a 3D printer (Stratasys, trade name: Object 260 Connex).
  • the 3D data used in the 3D printer was obtained by processing on a computer 3D data of a certain individual obtained from a three-dimensional image analysis system (trade name: Volume Analyzer SYNAPSE VINCENT, manufactured by Fujifilm Corporation).
  • 3D graphic software manufactured by E Frontier, trade name: Shade 3D was used.
  • liver parenchyma data was cut out by Boolean calculation.
  • VeroClear manufactured by Stratasys
  • VeroClear was used as the ink for the 3D printer, which is a female material.
  • the prepared PVA / gelatin aqueous solution was stirred for 3 hours while heating to 85 ° C., and then allowed to cool to about 60 ° C.
  • 0.60 g of food color red (manufactured by Kyoritsu Foods) and 0.06 g of food color green (manufactured by Kyoritsu Foods) are added and stirred to obtain a uniform composition. And colored.
  • the release agent was applied to the inner surface of the female mold, the molds were aligned and the joint surface was sealed. At this time, the blood vessel model and the bile duct model previously prepared and ice-cooled were placed in the female internal space.

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Abstract

L'invention concerne un procédé destiné à la production d'un modèle vasculaire d'un organisme qui permet de faciliter l'obtention d'un modèle vasculaire d'organisme, et un procédé destiné à la production d'un modèle d'un organe d'un organisme par utilisation du modèle vasculaire d'organisme obtenu à l'aide du procédé ci-dessus. Ce procédé destiné à la production d'un modèle vasculaire d'un organisme comporte : une étape pour mettre en contact une composition de précurseur qui contient de l'eau et un polymère aqueux avec la surface d'un moule mâle ayant une forme qui correspond à la forme d'une structure vasculaire d'un organisme, et recouvrir la surface du moule mâle avec un film de gel qui contient de l'eau et le polymère aqueux ; et une étape pour retirer le moule mâle à partir du film de gel, et obtenir un modèle creux comprenant le film de gel de la structure vasculaire de l'organisme.
PCT/JP2016/069403 2015-07-14 2016-06-30 Procédé pour produire un modèle vasculaire d'un organisme et procédé pour produire un modèle d'un organe d'un organisme WO2017010299A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019072873A (ja) * 2017-10-13 2019-05-16 富士ゼロックス株式会社 三次元造形物及び三次元造形物の製造方法
JP2021103204A (ja) * 2019-12-24 2021-07-15 泰弘 山本 臓器モデルの製造装置、臓器モデルの製造方法

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JP2011008213A (ja) * 2009-05-29 2011-01-13 Hitoo Okano 血管モデル
WO2012132463A1 (fr) * 2011-03-31 2012-10-04 国立大学法人神戸大学 Procédé de fabrication d'un modèle moulé tridimensionnel et d'un outil de support à des fins de traitement médical, de formation médicale, de recherche et d'enseignement
JP2014228803A (ja) * 2013-05-24 2014-12-08 ファインバイオメディカル有限会社 カテーテル手術シミュレータ及びそのアッセンブリ

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US7235592B2 (en) * 2004-10-12 2007-06-26 Zimmer Gmbh PVA hydrogel
JP2008070847A (ja) * 2006-09-13 2008-03-27 Seiichi Ikeda カテーテル手術シミュレータ
EP2540286A4 (fr) * 2010-02-26 2015-05-27 Nisshin Kasei Co Ltd Capsule dure et sa méthode de production

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011008213A (ja) * 2009-05-29 2011-01-13 Hitoo Okano 血管モデル
WO2012132463A1 (fr) * 2011-03-31 2012-10-04 国立大学法人神戸大学 Procédé de fabrication d'un modèle moulé tridimensionnel et d'un outil de support à des fins de traitement médical, de formation médicale, de recherche et d'enseignement
JP2014228803A (ja) * 2013-05-24 2014-12-08 ファインバイオメディカル有限会社 カテーテル手術シミュレータ及びそのアッセンブリ

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019072873A (ja) * 2017-10-13 2019-05-16 富士ゼロックス株式会社 三次元造形物及び三次元造形物の製造方法
JP2021103204A (ja) * 2019-12-24 2021-07-15 泰弘 山本 臓器モデルの製造装置、臓器モデルの製造方法

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