WO2015029707A1 - Trachée artificielle, procédé de production de trachée artificielle, et matériau de base pour former une trachée artificielle - Google Patents

Trachée artificielle, procédé de production de trachée artificielle, et matériau de base pour former une trachée artificielle Download PDF

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Publication number
WO2015029707A1
WO2015029707A1 PCT/JP2014/070551 JP2014070551W WO2015029707A1 WO 2015029707 A1 WO2015029707 A1 WO 2015029707A1 JP 2014070551 W JP2014070551 W JP 2014070551W WO 2015029707 A1 WO2015029707 A1 WO 2015029707A1
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Prior art keywords
cartilage
base material
tracheal
tissue
chondrocytes
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PCT/JP2014/070551
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English (en)
Japanese (ja)
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中山泰秀
古村眞
古村浩子
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独立行政法人国立循環器病研究センター
国立大学法人 東京大学
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Publication of WO2015029707A1 publication Critical patent/WO2015029707A1/fr

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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
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222—Gelatin
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/24—Collagen
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3612—Cartilage, synovial fluid
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3882—Hollow organs, e.g. bladder, esophagus, urether, uterus
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/22—Materials or treatment for tissue regeneration for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus

Definitions

  • the present invention relates to an artificial trachea having a plurality of tracheal cartilage portions, a method for producing an artificial trachea, and a base material for forming an artificial trachea.
  • Non-Patent Document 1 discloses that chondrocytes collected from an animal are attached to a non-woven mesh by being attached to a non-woven mesh and wound around the entire circumference of a mandrel. A technique for forming an artificial trachea by generating cartilage based on this is disclosed.
  • Non-Patent Document 2 a non-woven net with chondrocytes attached is placed in a spiral groove of a mandrel, and the non-patent document with fibroblasts attached around the entire circumference of the mandrel, By embedding this in the body of an animal, a technique has been disclosed in which cartilage is generated based on chondrocytes attached to a non-woven mesh and connective tissue is generated based on fibroblasts to form an artificial trachea. ing.
  • KOJI KOJIMA et al. “A composite tissue-engineered trachea useing sheep nasal chondrocycle and epithelial cells”, published in May 2003, The FASEB Journal. 17, pages 823-828 KOJI, KOJIMA et al., “Autologous tissue-engineered trachea with sheep nasal chondrocycles” page, June 2002, The Journal of Thoracic and Thoracic and Thoracic and Thoracic.
  • the original trachea has a structure in which a plurality of tracheal cartilages are spaced apart from each other in the airway direction, and a relatively flexible tracheal ligament is interposed between the tracheal ligaments, and the tracheal ligament connects a plurality of tracheal cartilages. It has become.
  • Non-Patent Document 1 a non-woven mesh with chondrocytes attached is wound around the entire circumference of a mandrel to generate cartilage, and the entire artificial trachea is formed by cartilage.
  • a non-woven mesh with chondrocytes attached is arranged in a helical groove of a mandrel to generate cartilage, and the helical cartilage is covered with connective tissue.
  • connective tissue Form an artificial trachea of structure.
  • the artificial trachea formed by the method has a different structure from the original trachea.
  • An object of the present invention is to provide an artificial trachea having the same structure as the original trachea, a method for producing an artificial trachea, and a base material for forming an artificial trachea.
  • an artificial trachea includes a plurality of tracheal cartilage portions made of cartilage tissue containing chondrocytes and a ring-shaped tracheal ligament portion made of connective tissue, and the plurality of tracheal cartilage portions The parts are provided at intervals in the airway direction, and are connected via the tracheal ligament part so that the tracheal cartilage part and the tracheal ligament part are formed in a tubular shape as a whole.
  • the tracheal cartilage portion is formed with the cartilage tissue
  • the tracheal ligament portion is formed with the connective tissue
  • the plurality of tracheal cartilage portions are provided at intervals
  • the tracheal ligament portions are connected with each other.
  • the tracheal cartilage portion may be integrated with the ring-shaped tracheal ligament portion and configured in a tubular shape as a whole, and the tracheal cartilage portion itself can be exemplified by a ring shape.
  • a tracheal cartilage portion having another shape such as a U-shape can be used as appropriate.
  • the “connective tissue” usually refers to a tissue mainly composed of collagen and formed in a living body.
  • This is a concept including a tissue corresponding to a connective tissue formed in a living body when the tissue is formed in an environment outside the living body.
  • the “tracheal ligament portion” in the artificial trachea of the present invention is composed of connective tissue, but in the description of the present specification and claims, it corresponds to the “tracheal ligament” of the original trachea. In this sense, the term “tracheal ligament” is used.
  • the periphery of the tracheal cartilage may be covered with connective tissue.
  • the tracheal cartilage portion and the tracheal ligament portion are not only connected between the tracheal cartilage portion by interposing the tracheal ligament portion, but also connecting the tracheal cartilage portion with the connective tissue. It can be integrated more firmly.
  • the present invention also provides a method for producing an artificial trachea having a plurality of tracheal cartilage portions. Specifically, an injection step of injecting a chondrocyte dispersion solution containing chondrocytes into a mold, and a gel body formation step of forming a gel body in which the chondrocyte dispersion solution is gelled to disperse the chondrocytes A mounting step of mounting a plurality of gel bodies on a columnar base material at intervals in the central axis direction, an installation step of placing the base material on which the gel bodies are mounted in an environment where biological tissue materials exist, and a gel Transforming the body into cartilage tissue to form a tracheal cartilage, forming a connective tissue around the base material, taking out the base material coated with the connective tissue from the environment, A separation step in which the tracheal cartilage and the connective tissue integrated from the material are peeled off as an artificial trachea.
  • a plurality of gel bodies in which chondrocytes are dispersed are attached to a base material at intervals, and in an environment where biological tissue material exists, the gel bodies are changed to cartilage tissue to thereby change the tracheal cartilage portion.
  • a plurality of tracheal cartilage portions can be connected and integrated with a connective tissue formed around the base material, and a plurality of tracheal cartilage portions are provided at intervals. Can be produced.
  • the “biological tissue material” is a substance necessary for forming a desired biological tissue, such as fibroblasts, smooth muscle cells, endothelial cells, stem cells, ES cells, iPS cells, etc.
  • the “biological tissue material” includes materials derived from mammals such as humans, dogs, cows, pigs, goats and sheep, birds, fish and other animals, or artificial materials equivalent thereto.
  • “in the environment where biological tissue material is present” means in vivo (for example, limbs, mammals such as humans, dogs, cows, pigs, goats, sheep, birds, fish, and other animals). It represents the inside of an artificial environment containing a biological tissue material outside the living body of an animal).
  • a holding material that holds the chondrocytes in a dispersed state may be inserted into the mold. According to this configuration, since the holding material is inserted into the mold, it is possible to hold the chondrocytes with this holding material and to reinforce the gel body, and to facilitate the handling of the gel body and the substrate on which the gel body is mounted. Can do.
  • the holding material may be formed from a material having biodegradability.
  • the holding material when the gel body is reinforced with the holding material and the gel body is changed to the cartilage tissue, the holding material can be disassembled, and the tracheal cartilage portion made of the cartilage tissue can be left without leaving the holding material.
  • the biodegradable material include biodegradable plastics such as polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxyalkanoate, and casein.
  • natural biodegradable plastics such as collagen and gelatin can be exemplified. A molecule can be exemplified.
  • the holding material is not limited to a biodegradable material, and a material formed from a material remaining in the cartilage tissue can be used.
  • a material formed from a material remaining in the cartilage tissue can be used.
  • a highly versatile material such as polyethylene, polyester, polyurethane, polycarbonate, and silicone can be used.
  • a molecule can be exemplified.
  • the cartilage tissue is collected from the living body, the chondrocytes are separated from the cartilage tissue and contained in the chondrocyte dispersion solution, and the substrate is embedded in the same living body from which the cartilage tissue is collected in the installation process. May be.
  • the original living body that separates the chondrocytes dispersed in the gel body and the living body as an environment that changes the gel body into cartilage tissue are the same living body, thereby preventing rejection reactions by the immune system.
  • transplantation of an artificial trachea in the same living body can prevent rejection due to transplantation.
  • chondrocytes induced to differentiate from iPS cells or stem cells, or stem cells before differentiation into chondrocytes may be used.
  • the chondrocytes can be placed in a plurality of locations on the base material by various methods, such as being attached to the base material by being contained in the gel body, or directly adhered to the base material.
  • a cartilage tissue can be formed on the basis of chondrocytes arranged at a plurality of locations on a base material to form a tracheal cartilage portion, and the same effect as the above method using a gel body can be achieved.
  • the present invention is a method for producing an artificial trachea having a plurality of tracheal cartilage portions, an arrangement step of arranging chondrocytes at a plurality of locations spaced in the central axis direction of a columnar base material, and a chondrocyte Placing the base material in an environment where biological tissue material is present, forming a cartilage tissue based on the chondrocytes to form a tracheal cartilage portion, and connecting a connective tissue around the base material A tissue forming step to be formed; a step of taking out the base material coated with connective tissue from the environment; and a separation step of peeling and taking out the tracheal cartilage and connective tissue integrated from the base material as an artificial trachea And a method for producing an artificial trachea.
  • a holding material for holding the chondrocytes in a dispersed state may be arranged at a plurality of locations on the base material.
  • the chondrocytes are held by the holding material, the chondrocytes are dispersed in the holding material arranged at a predetermined position of the base material, or the holding material in which the chondrocytes are dispersed is set at a predetermined position of the base material.
  • chondrocytes can be easily arranged at a plurality of locations on the base material.
  • a solution in which the chondrocytes are dispersed may be hung on the holding material, or the holding material may be immersed in the solution.
  • the holding material may be formed from a material having biodegradability.
  • chondrocyte aggregates may be arranged at a plurality of locations on the base material. According to this configuration, since the chondrocytes are aggregated and aggregated (spheroids), the chondrocytes can be handled to a certain size, for example, the chondrocytes are dispersed like a single cell. When the solution is dropped on the holding material, the chondrocytes do not pass through the holding material, and the chondrocytes can be easily arranged on the base material.
  • gel bodies in which chondrocytes are dispersed may be arranged at a plurality of locations of the base material.
  • cartilage tissue is collected from a living body, chondrocytes are separated from the cartilage tissue and placed on the base material, and the base material is placed on the same living body from which the cartilage tissue is collected in the installation step. You may make it embed.
  • the present invention also provides an artificial body having a plurality of tracheal cartilage portions by attaching a gel body in which chondrocytes are dispersed, or a holding material for holding chondrocytes in a dispersed state and placing it in an environment in which biological tissue material exists.
  • An artificial trachea-forming substrate for forming a trachea is provided.
  • a columnar base body on which a plurality of gel bodies or holding materials can be mounted, the gel body or the holding material, and the base body are covered from the outside, and the gel bodies or the holding materials are spaced apart in the central axis direction.
  • a positioning cover that is opened and positioned, and communicates the inside and outside of the positioning cover.
  • the positioning cover can prevent the positional displacement of the gel body or the holding material, and the inside and outside of the positioning cover. Therefore, the artificial trachea can be formed in the environment where the biological tissue material exists without being obstructed by the positioning cover.
  • the positioning protrusion since the positioning protrusion is formed on the base body, the positioning protrusion can prevent the positional deviation of the gel body or the holding material, and the base body is divided in the circumferential direction. After the trachea is formed, the base body can be divided and extracted from the artificial trachea without being hindered by the positioning protrusions.
  • a plurality of tracheal cartilage portions formed of cartilage tissue are provided at intervals from each other, and these are connected by a tracheal ligament portion formed of a relatively flexible connective tissue.
  • the artificial trachea can have a flexible structure as a whole with the same configuration as the original trachea.
  • Perspective view of an artificial trachea It is a figure which shows a mode that a gel body is formed, (a) shows an injection
  • an artificial trachea 1 includes a plurality of ring-shaped tracheal cartilage portions 2 made of cartilage tissue containing chondrocytes and a plurality of ring-shaped tracheal ligament portions 3 made of connective tissue.
  • the cartilage part 2 is provided at intervals in the airway direction, and a plurality of tracheal cartilage parts 2 are covered with connective tissue 4 and connected via the tracheal ligament part 3, and tracheal cartilage
  • the part 2 and the tracheal ligament part 3 are formed in a tubular shape having an airway 5 inside as a whole.
  • the tracheal cartilage portion 2 and the tracheal ligament portion 3 of the artificial trachea 1 are portions corresponding to the tracheal cartilage and tracheal ligament of the original trachea, respectively, and a relatively flexible tracheal ligament portion 3 is interposed between the tracheal cartilage portion 2.
  • the artificial trachea 1 has a flexible structure as a whole.
  • the tracheal cartilage portion 2 is not limited to a ring shape, and may be other shapes such as a U shape as appropriate in accordance with the original structure of the trachea.
  • the production method according to the present invention includes a “solution preparation step” for preparing a chondrocyte dispersion solution 6 that contains chondrocytes and can be gelled, and an “injection step” for injecting the chondrocyte dispersion solution 6 into the mold 7.
  • “Gel body forming step” in which the chondrocyte dispersion solution 6 is gelled to form a gel body 8 in which the chondrocytes are dispersed, and a plurality of gel bodies 8 are attached to the columnar base material 9 at intervals in the central axis direction.
  • the “tissue formation step” for forming the connective tissue 4 around the base material 9 and the “removal step” for taking out the base material 9 coated with the connective tissue 4 from the environment are integrated from the base material 9.
  • Exfoliated tracheal cartilage 2 and connective tissue 4 as artificial trachea 1 Take out Te consisting of a "separation process”.
  • ⁇ Solution preparation process First, an auricular cartilage tissue of an animal such as a rabbit is cut and collected with scissors, the cartilage tissue is cut into a size of about a rice grain with a scalpel, and then immersed in an enzyme that degrades collagen for a predetermined time (for example, 0.3 % Soaked in a solution of% COLLAGENASE type 2 at 37 ° C. for 1.5 hours).
  • an enzyme that degrades collagen for a predetermined time (for example, 0.3 % Soaked in a solution of% COLLAGENASE type 2 at 37 ° C. for 1.5 hours).
  • the collagen in the cartilage tissue mainly composed of collagen and chondroitin sulfate is decomposed to loosen the cartilage tissue, and the chondrocytes scattered in the cartilage tissue are separated.
  • the cartilage tissue In order to store the cartilage tissue for a short period of time until it is minced and immersed in the enzyme, the cartilage tissue is soaked in a basic synthetic medium such as F-12 medium (without serum). Thus, it is preferable to prevent the cartilage tissue from drying out.
  • a basic synthetic medium such as F-12 medium (without serum).
  • the solution containing the cartilage tissue in which collagen is decomposed is filtered using, for example, a 100 ⁇ m pore filter (cell strainer or the like) to obtain a solution containing chondrocytes, and the remaining cartilage tissue is removed.
  • the centrifuge is operated at a rotation speed of 1000 rpm for 5 minutes, and the solution containing chondrocytes obtained above is treated at room temperature to recover chondrocytes.
  • the collected chondrocytes may be cultured and increased by a well-known method.
  • the chondrocyte dispersion solution 6 containing chondrocytes and gelling can be added to the F-12 medium solution while adjusting the number of chondrocytes and mixed with an atelocollagen aqueous solution.
  • the solution mixed with the medium solution into which chondrocytes are charged may be any solution that gels in a state where chondrocytes are dispersed, and gelatin or the like can be used instead of atelocollagen.
  • chondrocytes induced to differentiate from iPS cells or stem cells can be used, or stem cells before differentiation into chondrocytes can be used.
  • the chondrocyte dispersion solution 6 is injected into the ring-shaped groove 11 of the mold 7 and a ring-shaped holding material 12 that holds the chondrocytes in a dispersed state is inserted.
  • the amount of the chondrocyte dispersion solution 6 to be injected into the holding material 12 having an inner diameter of 6 mm, an outer diameter of 10 mm, and a thickness of 1 mm is 125 ⁇ L, and the number of chondrocytes is 1 to 10 ⁇ 10 6 .
  • the shape and size of the ring groove 11 are appropriately set according to the shape of the trachea of the animal to be transplanted, and a groove having another shape such as a U shape may be adopted instead of the ring groove 11. .
  • the order of injection of the chondrocyte dispersion solution 6 into the ring-shaped groove 11 and insertion of the holding material 12 are not particularly limited, and the holding material 12 is inserted after the chondrocyte dispersion solution 6 is injected.
  • the chondrocyte dispersion solution 6 may be injected after the holding material 12 is inserted, or the remaining chondrocytes after the chondrocyte dispersion solution 6 is injected halfway and the holding material 12 is inserted.
  • the dispersion solution 6 may be injected.
  • the holding material 12 is, for example, a sponge formed from a biodegradable material such as polylactic acid. Like the ring-shaped groove 11, the holding material 12 has a shape and a size according to the shape of the trachea of the animal to be transplanted. Is appropriately set.
  • the holding material 12 may be any material that can be used as a scaffold to which chondrocytes can be attached. Instead of a sponge-like material, a solid having a communicating hole, cotton, fiber, mesh, or the like can be used. Further, the holding material 12 can be omitted. Further, as the material for the holding material 12, biodegradable plastics such as polyglycolic acid, polycaprolactone, polyhydroxyalkanoate, and casein, or natural polymers such as collagen and gelatin, should be employed instead of polylactic acid. In addition, as a non-biodegradable material, a general-purpose polymer used in medical devices such as polyethylene, polyester, polyurethane, polycarbonate, and silicone can be used.
  • chondrocyte dispersion solution 6 As shown in FIG. 2B, the mold 7 in which the chondrocyte dispersion solution 6 is injected into the ring-shaped groove 11 is left at 37 ° C. for 2 hours. As a result, the atelocollagen contained in the chondrocyte dispersion solution 6 is solidified in a jelly shape, and the chondrocyte dispersion solution 6 is gelled to obtain a ring-shaped gel body 8 in which chondrocytes are dispersed. In addition, when using the chondrocyte dispersion solution 6 prepared by mixing gelatin instead of atelocollagen, the chondrocyte dispersion solution 6 may be gelated by leaving the mold 7 cooled to 4 ° C.
  • a plurality of gel bodies 8 are spaced apart by about 1 mm, for example, by passing a cylindrical base material 9 through a central hole of the gel body 8. Attach to 9 at almost equal intervals.
  • interval of the gel body 8 according to the shape of the trachea of the animal to be transplanted not only 1 mm.
  • the base material 9 is set to have the same diameter as the inner diameter of the gel body 8 so as to prevent the backlash of the gel body 8, for example, about 6 mm.
  • general-purpose plastics used in the medical field such as acrylic and silicone can be used, and glass, ceramics, metals, and the like can be used besides them.
  • the base material 9 on which the plurality of gel bodies 8 are mounted in the mounting step is embedded in, for example, the subcutaneous or intraperitoneal cavity of a rabbit from which the cartilage tissue is collected.
  • the base material 9 is preferably embedded in the same living body from which the cartilage tissue is collected. However, if the biological tissue material is present, the base material 9 should be installed in another environment. Also good.
  • the living body of the animal for example, subcutaneous in the extremity, shoulder, back, abdomen, etc., or in the abdominal cavity having a volume for receiving the base material 9 and the gel body 8
  • an artificial environment such as in a solution in which a living tissue material floats outside an animal.
  • the biological tissue material those derived from humans, dogs, cows, pigs, goats, rabbits, sheep, other mammals, those derived from birds, fish, other animals, or artificial materials can be used.
  • the gel body 8 is changed to a ring-shaped cartilage tissue 10 and the surface of the cartilage tissue 10 is formed around the base material 9.
  • the tracheal cartilage portion 2 is formed by being covered with the membranous connective tissue 4.
  • the connective tissue 4 enters between the base material 9 and the cartilage tissue 10 and covers the entire cartilage tissue 10.
  • the periphery of the base material 9 between the tracheal cartilage portions 2 is covered with the connective tissue 4 integrally with the cartilage tissue 10 to form a ring-shaped tracheal ligament portion 3, and a plurality of tracheal cartilage portions 2 are composed of tracheal ligaments.
  • the parts 3 are connected and integrated.
  • the connective tissue 4 is composed of an extracellular matrix such as fibroblasts and collagen.
  • a removal step of taking out the base material 9 from the environment where the biological tissue material exists is performed.
  • the base material 9 taken out from the environment in which the biological tissue material exists is covered with a film of the connective tissue 4 on the entire surface including both end faces.
  • immunogen removal treatment such as decellularization treatment, dehydration treatment, and fixation treatment in order to prevent rejection after transplantation.
  • decellularization include ultrasonic treatment, surfactant treatment, and enzyme treatment such as collagenase to elute and wash the extracellular matrix.
  • Dehydration methods include methanol, ethanol, isopropyl alcohol, etc. There is a method of washing with a water-soluble organic solvent, and as a method of fixing, there is a method of treating with an aldehyde compound such as glutaraldehyde or formaldehyde.
  • this invention is not limited to said embodiment, A change can be suitably added within the scope of the present invention.
  • a base material 13 that prevents the movement of the gel body 8 may be employed instead of the cylindrical base material 9 as described above.
  • the base material 13 is a cylindrical base material body 14 on which a plurality of gel bodies 8 can be mounted, and the gel body 8 and the base body body 14 are covered from the outside, and the gel bodies 8 are positioned at intervals in the central axis direction.
  • a positioning cover 15 is a cylindrical base material body 14 on which a plurality of gel bodies 8 can be mounted, and the gel body 8 and the base body body 14 are covered from the outside, and the gel bodies 8 are positioned at intervals in the central axis direction.
  • the positioning cover 15 is formed to have a size that covers the base body 14, and a plurality of gel body accommodating portions 16 that are set to have a large diameter and accommodate and position the gel body 8 are formed at intervals in the axial direction. ing.
  • the positioning cover 15 is formed in a grid shape with a coarse mesh and communicates inside and outside, and prevents the formation of the tracheal cartilage portion 2 and the tracheal ligament portion 3 from being hindered in the tissue formation process.
  • the base body 18 is divided into a plurality of parts in the circumferential direction, and is arranged around a cylindrical core member 20 and is configured in a cylindrical shape by covering the end portion with a fixing ring 21 and fixing it.
  • the base material 17 is removed in the separation process by removing the fixing ring 21 and extracting the core material 20 and disassembling the base material body 18 into a plurality of parts.
  • the base material main body 18 can be extracted from the artificial trachea 1 without hooking the positioning protrusion 19 on 2.
  • chondrocyte aggregates are held in a dispersed state only by the holding material 12, and the holding material 12 is held in the base materials 9 and 13. , 17 may be attached.
  • a solution in which the chondrocyte aggregate is dispersed on the holding material 12 attached to the base material 9, 13, 17 is dropped, The holding material 12 is immersed in the solution and then mounted on the base materials 9, 13, and 17.
  • chondrocyte aggregates may be directly bonded to the base material 9 without using the gel body 8 or the holding material 12. Further, the chondrocytes may be dispersed and held on the holding material 12 alone without using chondrocyte aggregates by using a fine holding material 12 or the like.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Botany (AREA)
  • Vascular Medicine (AREA)
  • Reproductive Health (AREA)
  • Rheumatology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

La présente invention concerne une trachée artificielle ayant la même structure qu'une trachée naturelle. Spécifiquement, la trachée artificielle est pourvue de sections de cartilage trachéen multiples (2) obtenues à partir de tissu de cartilage (10) contenant des chondrocytes, et de sections de ligament trachéen en forme d'anneau (3) obtenues à partir de tissu conjonctif (4). Les sections de cartilage trachéen multiples (2) sont disposées dans la direction du tractus respiratoire en laissant des espaces entre celles-ci. Les sections de cartilage trachéen multiples (2) sont raccordées par l'intermédiaire des sections de ligament trachéen (3). Les sections de cartilage trachéen (2) et les sections de ligament trachéen (3) configurent une forme globale tubulaire. Les sections de ligament trachéen relativement souples (3) sont intercalées entre les sections de cartilage trachéen multiples (2). La trachée artificielle (1) a une structure qui est globalement pliable. La trachée artificielle (1) a une structure qui est la même que celle de la trachée naturelle.
PCT/JP2014/070551 2013-08-28 2014-08-05 Trachée artificielle, procédé de production de trachée artificielle, et matériau de base pour former une trachée artificielle WO2015029707A1 (fr)

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JP2013177328A JP2015043892A (ja) 2013-08-28 2013-08-28 人工気管、人工気管の生産方法、及び人工気管形成用基材
JP2013-177328 2013-08-28

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017131241A1 (fr) * 2016-01-29 2017-08-03 国立研究開発法人国立循環器病研究センター Amas cellulaire, structure cellulaire et corps tissulaire tridimensionnel
CN109481734A (zh) * 2019-01-11 2019-03-19 上海市肺科医院 一种生物性高仿生人工气管的制备方法
US11149252B2 (en) 2016-01-29 2021-10-19 National Cerebral And Cardiovascular Center Cell mass, cell structure, and three-dimensional tissue body

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200012954A (ko) * 2017-05-30 2020-02-05 트라우마 케어 컨설트 연골 그래프트 스캐폴드

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
AYUKO YASUDA ET AL.: "Atarashii Ondo Kan'osei hydrogel o Mochiita Kikan Saisei eno Torikumi", JAPANESE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, vol. 53, September 2005 (2005-09-01), pages 399 *
KOMURA M. ET AL.: "Human tracheal chondrocytes as a cell source for augmenting stenotic tracheal segments: the first feasibility study in an in vivo culture system.", PEDIATRIC SURGERY INTERNATIONAL, vol. 24, no. 10, 2008, pages 1117 - 1121 *
LIU L. ET AL.: "Novel strategy to engineer trachea cartilage graft with marrow mesenchymal stem cell macroaggregate and hydrolyzable scaffold.", ARTIFICIAL ORGANS, vol. 34, no. 5, 2010, pages 426 - 433 *
MIKA NOMOTO ET AL.: "Jika Nankotsu Saibo o Donyu shita Shinki Jinko Kikan no Kaihatsu", THE OTO-RHINO-LARYNGOLOGICAL SOCIETY OF JAPAN , INC., vol. 115, no. 4, 2012, pages 506, 516 *
NAITO H. ET AL.: "Engineering bioartificial tracheal tissue using hybrid fibroblast- mesenchymal stem cell cultures in collagen hydrogels.", INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY, vol. 12, no. 2, 2011, pages 156 - 161 *
WU W. ET AL.: "Tissue engineering of trachea- like cartilage grafts by using chondrocyte macroaggregate: experimental study in rabbits.", ARTIFICIAL ORGANS, vol. 31, no. 11, 2007, pages 826 - 834 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017131241A1 (fr) * 2016-01-29 2017-08-03 国立研究開発法人国立循環器病研究センター Amas cellulaire, structure cellulaire et corps tissulaire tridimensionnel
US11149252B2 (en) 2016-01-29 2021-10-19 National Cerebral And Cardiovascular Center Cell mass, cell structure, and three-dimensional tissue body
US11697797B2 (en) 2016-01-29 2023-07-11 National Cerebral And Cardiovascular Center Manufacturing method of a cell structure
CN109481734A (zh) * 2019-01-11 2019-03-19 上海市肺科医院 一种生物性高仿生人工气管的制备方法
CN109481734B (zh) * 2019-01-11 2023-09-19 上海市肺科医院 一种生物性高仿生人工气管的制备方法

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