WO2015029891A1 - 結合組織体形成用基材、及び結合組織体の生産方法 - Google Patents
結合組織体形成用基材、及び結合組織体の生産方法 Download PDFInfo
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- WO2015029891A1 WO2015029891A1 PCT/JP2014/071985 JP2014071985W WO2015029891A1 WO 2015029891 A1 WO2015029891 A1 WO 2015029891A1 JP 2014071985 W JP2014071985 W JP 2014071985W WO 2015029891 A1 WO2015029891 A1 WO 2015029891A1
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- connective tissue
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- cutting line
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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
- A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
- A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
- A61F2/2415—Manufacturing methods
-
- 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
- A61L27/3641—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 site of application in the body
- A61L27/3645—Connective tissue
-
- 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
- A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3695—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
-
- 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
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
- A61F2240/002—Designing or making customized prostheses
- A61F2240/004—Using a positive or negative model, e.g. moulds
-
- 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
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0096—Markers and sensors for detecting a position or changes of a position of an implant, e.g. RF sensors, ultrasound markers
- A61F2250/0097—Visible markings, e.g. indicia
-
- 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
- A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2535/00—Supports or coatings for cell culture characterised by topography
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2539/00—Supports and/or coatings for cell culture characterised by properties
Definitions
- the present invention relates to a substrate for forming a connective tissue body for forming a membranous connective tissue body, and a method for producing the connective tissue body.
- Patent Document 4 discloses a stent in which a valve body is formed integrally with a connective tissue layer covering the stent intermediate body by covering the stent intermediate body with a connective tissue layer and providing a cut in the tissue body. Has been.
- JP 2007-312821 A JP 2008-237896 A JP 2010-094476 A JP 2007-037763 (paragraph numbers 0037, 0044, 0045, FIG. 1)
- the invention described in Patent Document 4 forms a valve body by cutting an artificially formed connective tissue body, and the connective tissue body is flexible and easily deformed. It is relatively difficult to cut accurately into the shape of this, and it tends to be a careful work. Moreover, since it takes a lot of time and effort to artificially form a connective tissue body, a technique for cutting the connective tissue body into an accurate shape without failure is required.
- An object of the present invention is to provide a substrate for forming a connective tissue capable of accurately cutting a connective tissue into a predetermined shape, and a method for producing the connective tissue.
- the connective tissue-forming substrate according to the present invention is for forming a film-like connective tissue on the surface thereof by placing it in an environment where biological tissue materials exist.
- a processed mark forming portion for forming a mark for processing the connective tissue body is formed on the substrate surface.
- the processed mark forming portion is formed on the surface of the base material, when the film-like connective tissue is formed on the surface of the base material, the mark is formed by intruding the connective tissue into the processed mark forming portion. It is possible to form a membrane-like connective tissue that can be accurately processed into a predetermined shape at the position of the mark.
- the processed mark forming portion may be a concave portion, a convex portion, or a combination thereof, but by forming the processed mark forming portion on the substrate surface as a concave portion, the mark is formed with a convex portion made of connective tissue.
- the mark can be made conspicuous and the membranous connective tissue can be processed more easily than the case where the mark is formed of a recess.
- 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).
- connective tissue usually refers to a tissue mainly composed of collagen and formed in the living body, but in the description of the present specification and claims, it is a living tissue. It is a concept including a tissue corresponding to a connective tissue formed in the body when the tissue is formed in an ex vivo environment.
- a cutting line forming groove for forming a cutting line when cutting connective tissue can be exemplified.
- the cutting line forming groove is formed on the surface of the substrate, when forming a film-like connective tissue body on the surface of the substrate, the cutting line is formed by allowing the connective tissue to enter the cutting line forming groove. It is possible to form a membrane-like connective tissue body that can be precisely cut into a predetermined shape along the cutting line.
- the cutting line can be constituted by the protrusion made of the connective tissue, and the cutting line is configured in the groove shape.
- the connective tissue body is cut along the outside of the cutting line so as to leave the cutting line of the ridge, the cutting edge of the membranous connective tissue body is reinforced by the ridge forming the cutting line. can do.
- examples of the processed mark forming part include a folded mark forming part that forms a folded mark when the connective tissue body is folded.
- the folded mark forming portion is formed on the substrate surface, when forming a film-like connective tissue on the substrate surface, the folded tissue is formed by intruding the connective tissue into the folded mark forming portion. Therefore, it is possible to form a membrane-like connective tissue body that can be accurately folded into a predetermined shape at the position of the folding mark.
- a stop attention mark forming portion that forms a stop attention mark when the connective tissue body is fastened can be exemplified.
- the stop target mark forming part is formed on the substrate surface, when forming a film-like connective tissue body on the substrate surface, the connective tissue is caused to enter the stop target mark forming part to stop the target mark.
- a film-like connective tissue body that can be accurately fixed to a predetermined shape at the position of the stop target mark can be formed.
- a ridge forming groove for forming a ridge on the connective tissue body may be formed on the substrate surface separately from the processing mark forming portion.
- ridge forming groove is formed separately from the processed mark forming portion, in addition to the processed mark, a ridge can be formed separately from the processed mark. Can be used as another mark for grasping the shape and orientation of the connective tissue body to make it easy to find the work mark.
- a protruding line forming groove for forming a protruding line on the connective tissue is formed on the substrate surface separately from the cutting line forming groove, and the protruding line forming groove is formed. May be arranged in parallel with the cutting line forming groove and the groove width direction.
- the connective structure formed on the surface of the base material can be formed with another protrusion adjacent to the protrusion forming the cutting line and the groove width direction. Since the strip is formed, the cut line of the connective tissue body can be found more easily. Moreover, by cutting the connective tissue body along the cutting line, another protrusion can be left along the cutting edge, and the cut edge of the connective tissue body can be reinforced with the remaining protrusion. . Moreover, it can replace with a cutting
- the protrusion forming groove may be a thickening groove for thickening and reinforcing the connective tissue body. According to this configuration, it is possible to reinforce and thicken the connective tissue by forming a ridge in the ridge forming groove as the thickening groove, and to make it easier to grasp the shape and orientation of the connective tissue, and the connective tissue It is possible to form a ridge having a function of reinforcing and reinforcing the body.
- the present invention also provides a method for producing a membranous connective tissue body composed of connective tissue. Specifically, an installation process in which a substrate having a cutting line forming groove on the surface of the substrate is placed in an environment where biological tissue material exists, and the connective tissue is cut while forming the connective tissue around the substrate. Forming process for forming cutting lines by intruding into the line forming groove, taking out the substrate covered with connective tissue from the environment, and peeling the connective tissue covering the substrate surface as a membrane-like connective tissue body And a separation step of removing the connective tissue body along the cutting line.
- the connective tissue in the forming step, is allowed to enter the cutting line forming groove on the substrate surface, and a cutting line is formed at an accurate position of the film-like connective tissue formed on the substrate surface,
- the connective tissue body in the cutting step, can be cut along the cutting line, and the membranous connective tissue body can be accurately cut into a predetermined shape.
- a cutting line may be formed, but another processing mark such as a turn mark or a stop mark may be formed.
- the present invention is a method for producing a membranous connective tissue body comprising a connective tissue, and a step of placing a base material having a processing mark forming portion on the surface of the base material in an environment in which a biological tissue material exists; A forming step of forming a mark by intruding the connective tissue into the processed mark forming portion while forming a connective tissue around the base material, and taking out the base material coated with the connective tissue from the environment And a separation step of separating and taking out the connective tissue covering the surface of the base material as a membranous connective tissue, and a processing step of processing the connective tissue at the position of the mark, A method for producing connective tissue is provided.
- the cutting line forming groove is formed on the surface of the substrate forming the membrane-like connective tissue, and the cutting line is formed in the connective tissue.
- the connective tissue body can be cut along. This makes it possible to cut a flexible, easily deformable membranous connective tissue into a predetermined shape without failure while requiring a lot of time and labor for artificial formation.
- the perspective view seen from the front end side of the artificial valve formed using the base material for connective tissue formation concerning the present invention Perspective view from the base end side of the artificial valve Longitudinal section showing attachment of prosthetic valve to the heart
- the perspective view which shows the valve closing state of an artificial valve The perspective view of the base material for connective tissue formation concerning the present invention
- Diagram showing the procedure for producing an artificial valve Perspective view of another form of connective tissue forming substrate
- Perspective view of an artificial valve with folded structure Perspective view of a base material for connective tissue formation used in the production of an artificial valve with a folded structure
- the prosthetic valve 1 can be transplanted to a site having a short length in the flow direction, and is used, for example, as a mitral valve for partitioning the left chamber 3 and the left atrium 4 of the heart 2.
- a tubular valve body 5 made of connective tissue, the proximal end portion of the valve body 5 being a fastening portion 6 that can be fastened to a site where the artificial valve 1 is implanted, String-like chords 7 are extended from a plurality of locations in the circumferential direction.
- the valve body 5 has a substantially frustoconical cylindrical shape whose peripheral length on the distal end side is set to be smaller than that on the proximal end side, and the central hole 8 is pushed and widened by the pressure of the fluid trying to pass through the central hole 8. The central hole 8 is crushed and closed.
- the fastening portion 6 is thicker and reinforced than other portions of the valve body 5 and has sufficient strength to fasten to the heart 2 or the like without impairing the flexibility of the valve body 5. ing.
- chords 7 are formed in a string-like and smooth tapered shape, and a total of four chords 7 are extended to the tip side one by one from four points set at substantially equal intervals in the tip of the valve body 5.
- the chordal tip 13 is fixed to the tip of the valve body 5.
- the tip of the valve body 5 is fastened to the transplanted site via the chords 7, and the attachment positions of the four chords 7 are set close to the top and bottom and left and right to set the valve body 5.
- the valve body 5 to be crushed up and down is configured such that the upper half is the front leaf 14 and the lower half is the rear leaf 15, and the front leaf 14 and the back leaf 15 are in contact with each other to close the valve. .
- chord 7 is composed of the same “connective tissue” as the “connective tissue” constituting the valve body 5, but in the description of the present specification, the term “chondrum” is used as it is.
- the prosthetic valve 1 has, for example, a fastening part 6 of the valve body 5 fastened between the left ventricle 3 and the left atrium 4 of the heart 2, and a chordal tip 13 of the chord chord 7 to the chamber wall of the left ventricle 3.
- the heart 2 is implanted as an artificial mitral valve (see FIG. 3).
- FIG. 3 is a cross-sectional view of the heart 2, and shows a cross section in a vertical plane passing through the left ventricle 3, the left atrium 4, the right ventricle 16, the aorta 17, and the aortic valve 18.
- the prosthetic valve 1 implanted as a prosthetic mitral valve in the heart 2 applies blood pressure to the outer surface of the substantially frustoconical cylindrical valve body 5 to crush the central hole 8;
- the front leaflet 14 and the back leaflet 15 come into contact with each other to close the valve, thereby preventing blood flow from the left ventricle 3 toward the left atrium 4 (see FIG. 4).
- the central hole 8 of the valve body 5 is expanded and opened by the blood flow.
- the distal end portion of the valve body 5 is fastened by the chord 7, so that when the valve is closed, the distal end portion of the valve body 5 is prevented from being pushed into the left atrium 4 by the blood pressure.
- the chords 7 are prevented from obstructing the valve 5 from closing. Is done.
- connective tissue-forming substrate 19 according to the present invention used when producing a membranous connective tissue like the artificial valve 1 will be described.
- the base material 19 is for forming a membrane-like connective tissue body 20 that can be processed into the prosthetic valve 1 on its surface by placing it in an environment where biological tissue material exists.
- a cutting line forming groove 28 for forming a protrusion as a cutting line 31 when cutting the connective tissue body 20 on the surface of the substrate, and a reinforcing protrusion is formed on the connective tissue body 20 to increase the thickness.
- a thickening groove 29 to be reinforced is formed separately.
- This base material 19 is extended from the valve body forming part 21 which forms the site
- the chordal chord 7 is formed with a chordae forming portion 22 that forms a processable portion, and the valve body forming portion 21 and the chordae forming portion 22 are adjacent to each other in the central axis direction so as to be columnar as a whole. Composed.
- the valve body forming portion 21 has a circular base end section and a square with a diagonal section whose length is substantially the same as the diameter of the base end section, and smoothly connects the two cross sections.
- the peripheral length on the distal end side is set smaller than that on the proximal end side.
- a notch 23 that is continuous in the circumferential direction is formed at the base end of the valve body forming portion 21, and the base end side of the notch 23 is closed by a flange 24 to form a groove 25.
- the flange 24 is formed in a disc shape having a diameter substantially the same as the base end of the valve body forming portion 21, and a circular protrusion 26 protruding from one surface thereof is formed into a fitting hole that opens to the base end side of the valve body forming portion 21. It can be fitted and can be freely attached to and detached from the base end side of the valve body forming portion 21.
- reference numeral 27 denotes a knob for attaching and detaching the flange 24.
- the chordae forming part 22 is a rectangular parallelepiped having the same cross-sectional shape and the same size as the tip of the valve body forming part 21, and is formed adjacent to the tip side of the valve body forming part 21.
- Cutting line forming grooves for forming protrusions as cutting lines 31 on the side surfaces of the chord forming part 22 in the connective tissue body 20 formed on the surface of the chord forming part 22 when cutting the chords into the chord 7 28 is formed.
- the cutting line forming groove 28 is formed in a substantially arch shape so as to partition a tapered range near the corner of the chord forming part 22 from the central part.
- Convex ridges are formed at the corners of the valve element 5 and the chords 7 formed on the surface of the base material 19 at the respective corners of the valve element forming part 21 and the chords forming part 22 in the direction of the central axis.
- a thickening groove 29 for reinforcing the thickness is formed.
- the thickening grooves 29 reinforce the corner portions of the valve body 5 and the chord 7 to reinforce corner portions that tend to be weak points of the valve body 5 and the chord 7.
- the positions of the corner portions are indicated by the protrusions, and the orientation of the connective tissue body 20 and the position of the cutting line can be easily grasped.
- the material of the base material 19 has a strength (hardness) that does not greatly deform when embedded in a living body, has chemical stability, is resistant to a load such as sterilization, and stimulates the living body.
- a resin having no or little eluate is preferable, and examples thereof include, but are not limited to, a silicone resin and an acrylic resin.
- the thickness of the artificial valve 1 is determined by the outer diameter of the base material 19, the diameter can be changed according to the target thickness.
- an “assembly process” in which the columnar base material 19 is assembled while forming the groove portion 25, and the base material 19 having the cutting line forming groove 28 on the surface of the base material is used as the biological tissue material.
- “Installation process” that is placed in an environment in which the cutting line 31 is formed and the cutting line 31 is formed by allowing the connective tissue 30 to enter the cutting line forming groove 28 while forming the connective tissue 30 around the base material 19.
- FIG. 6 (a) to (d) show side views, and (e) and (f) show a cross-sectional view of the upper half and a side view of the lower half.
- the base material 19 having the cutting line forming groove 28 on the surface of the base material is placed in an environment where the biological tissue material is present (FIG. 6B).
- the environment in which the biological tissue material exists includes in an animal's living body (for example, subcutaneously or intraperitoneally embedded) or in an artificial environment such as a solution in which the biological tissue material floats outside the animal's body.
- biological tissue materials materials derived from other mammals such as humans, dogs, cows, pigs, goats, rabbits, sheep, birds, fish, other animals, or artificial materials can also be used.
- the base material 19 When embedding the base material 19 in an animal, it is performed with a minimum of incision under sufficient anesthesia, and the wound is sutured after implantation.
- an embedding site of the base material 19 for example, intraperitoneal cavity having a volume for receiving the base material 19, or subcutaneous such as an extremity, a shoulder or a back, and an abdomen are preferable.
- the implantation is performed by a minimally invasive method and the spirit of animal welfare is respected, and is performed with a minimum of incision under sufficient anesthesia.
- various culture conditions may be prepared and cell culture may be performed in a clean environment according to a known method.
- connective tissue 30 when the connective tissue 30 enters the cutting line forming groove 28, a protrusion is formed in the connective tissue body 20 to form the cutting line 31, and the connective tissue 30 enters the thickening groove 29, thereby A protrusion is formed at the corner portion of the tissue body 20 to be thickened and reinforced.
- the connective tissue 30 is composed of an extracellular matrix such as fibroblasts and collagen.
- a take-out process for taking out the base material 19 from the environment in which the biological tissue material exists is performed.
- the base material 19 taken out from the environment in which the biological tissue material exists is covered with a film of the connective tissue 30 on the entire surface including both end faces thereof.
- an immunogen removal process such as a decellularization process, a dehydration process, and a fixing process.
- 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.
- this embodiment has substantially the same configuration as the first embodiment, as shown in FIG. 7, instead of a base material 19 having a circular base end section and a square end section as a connective tissue-forming base material.
- a flat substrate 32 is employed.
- the valve body forming portion 33 of the base material 32 has an oval base end section and a rectangular shape with a tip section inscribed in the ellipse of the base end section.
- the peripheral length on the distal end side is set smaller than that on the proximal end side.
- the chord forming part 34 of the base material 32 is a rectangular parallelepiped having the same shape and the same size as the tip of the valve body forming part 33.
- Double grooves are formed on the side surface of the base material 32, the inner groove of the arch shape is used as a cutting line forming groove 35, and the outer groove of the arch shape reinforces the side edge of the chord chord 7 with increased thickness.
- the thickening groove 36 is formed. Thereby, the cutting line forming groove 35 and the thickening groove 36 are juxtaposed in the groove width direction, and a double protrusion including the cutting line 31 is formed on the connective tissue body 20 to cut the connective tissue body 20. When doing so, the cutting line 31 is made conspicuous to make it easy to find.
- the prosthetic valve 1 formed using the base material 32 is positioned such that the ridge formed by the thickening groove 36 is along the cutting edge, and reinforces the side edge of the chord 7.
- a chord chord narrower than 7 can be formed.
- the prosthetic valve 1 can be arranged such that the chords 7 are arranged at unequal intervals so that the bases of the upper and lower chords 7 in the valve-opened state are close to the top and bottom because the chord forming part 34 has a rectangular cross section. The resistance by the chord chord 7 when the valve body 5 is crushed up and down to close the valve can be further reduced.
- This embodiment has substantially the same configuration as that of the second embodiment, but the fastening portion is formed in the same thickness as other portions without increasing the thickness of the fastening portion of the artificial valve.
- an artificial valve is formed using a base material 38 that does not have the groove portion 25 at the proximal end portion of the valve body forming portion 33.
- a plurality of valve body cutting line forming grooves 39 a, 39 b, 39 c, 39 d, 39 e that are continuous in the circumferential direction are formed at the proximal end portion of the valve body forming portion 33 of the base material 38.
- a cutting line is formed.
- the size of the valve body 5 can be adjusted by cutting the connective tissue body 20 along a cutting line appropriately selected from a plurality of cutting lines according to the transplant site.
- the opening shape of the fastening part of the valve body 5 can also be adjusted by cutting the valve body 5 diagonally using a plurality of cutting lines as marks.
- An arch-shaped cutting line forming groove 40 is formed in the chord forming part 34 of the base material 38, and the vicinity of the arch-shaped top part branches into a plurality of branch grooves 40a, 40b, 40c, 40d, 40e.
- a cutting line that is formed and branches into a plurality of connective tissue bodies 20 is formed.
- the size of the valve body 5 and the length of the chordal cord 7 can be adjusted by cutting the connective tissue body 20 along the appropriately selected cutting line according to the transplant site from among the branched cutting lines. .
- the present embodiment has substantially the same configuration as the first to third embodiments, but produces an artificial valve 41 having a structure in which one end is folded back.
- the artificial valve 41 is used, for example, as the aortic valve 18 or the like, and has an outer tube portion 42 made of a connective tissue 50 and a cylindrical shape provided inside the outer tube portion 42.
- the valve body 43 is comprised,
- the some leaflet 44 which opens and closes the flow path X inside the valve body 43 is comprised.
- the valve body 43 has a shape in which one end of the outer tube portion 42 is folded inward at the turn-up portion 45, and the valve body 43 forms a plurality of leaflets 44, so that the valve body 43 is at the corrugated fastening portion 46. It is fixed to the inner surface of the outer tube portion 42.
- the fastening portion 46 is formed by fastening the valve body 43 to the outer tube portion 42 along a corrugated fastening line having a vertex at a plurality of the tip portions, and the fastening portion 46 is a valve leaf 44.
- the support part is configured.
- the method for fastening the valve body 43 to the outer tube portion 42 is not particularly limited, and examples thereof include sewing, adhesion, and fastening with a stapler.
- the leaflets 44 are configured one by one for each wave of the fastening portion 46, and a plurality of leaflets 44 are juxtaposed in the circumferential direction of the artificial valve 41.
- the leaflets 44 When there is a blood flow or the like from the distal end side to the proximal end side (from the upper side to the lower side in FIG. 9), the leaflets 44 are bent inward by receiving pressure at the distal ends of the leaflets 44.
- the flow path X inside the valve body 43 is closed.
- the leaflets 44 receive pressure on the distal end portions of the respective leaflets 44, and the leaflets 44 bent inward are returned.
- the leaves 44 are separated from each other, the flow path X inside the valve body 43 is opened.
- valve leaf 44 reciprocates inward and outward in the radial direction in accordance with the reversal of the direction of blood flow and the like, so that the flow path X inside the valve body 43 is opened and closed.
- 43 functions as an aortic valve that has three leaflets and opens and closes the aorta in the direction of blood flow.
- the base material 47 is for forming a tubular connective tissue body 51 that can be processed into the artificial valve 41 on the surface of the base material 47 by placing the base material 47 in an environment where biological tissue material exists.
- a cylindrical shape that forms a tubular connective tissue body 51 on the surface is formed.
- the base material 47 has a length in the central axis direction so that an artificial valve 41 having a tubular valve body 43 inside the outer tube portion 42 can be formed by folding one end of the tubular connective tissue body 11 inward. Is set longer than the sum of the length in the central axis direction of the outer tube portion 42 of the artificial valve 41 and the length in the central axis direction of the valve body 43.
- a turn-up mark forming groove 48 is formed as a turn-up mark forming portion continuous in the circumferential direction so as to form a turn-up mark 48a when the connective tissue body 51 is turned up. It has become.
- a corrugated stop target mark forming groove 49 as a stop target mark forming portion is formed on one end side of the base material 47 so as to form a stop target mark 49a when the connective tissue body 51 is fixed. It has become.
- a columnar base material 47 is placed in an environment where biological tissue material is present, and a membrane-like connective tissue 50 is formed around the base material 47.
- a “fastening step” for fastening to the outer pipe portion 42.
- the base material 47 is placed in an environment where the biological tissue material exists (FIG. 11 (a)).
- a take-out process for taking out the base material 47 from the environment where the biological tissue material exists is performed.
- the base material 47 taken out from the environment in which the biological tissue material exists is covered with a film of connective tissue 50 on the entire surface including both end faces.
- the position of the folding mark 48a is the folding part 45, one end of the tubular connective tissue body 51 is folded inward, the outer part is the outer tube part 42, and the folded part is the valve body 43.
- a cylindrical valve body 43 is formed inside the tube portion 42 (FIG. 11 (d)).
- a corrugated fastening portion 46 is formed by fastening a valve body 43 folded back inside the outer tube portion 42 to the inner surface of the outer tube portion 42 along the corrugated fastening mark 49a.
- the valve body 43 constitutes a plurality of leaflets 44 with one wave portion of the fastening portion 46 as a support portion, and an artificial valve 41 in which a plurality of leaflets 44 are provided inside the outer tube portion 42 is obtained. (FIG. 11 (e)).
- the artificial valve 1 in the first to third embodiments is not limited to being used as an artificial mitral valve, but by appropriately setting the number of chords 7 and their fixing positions, for example, the right ventricle of the heart It can also be used as another artificial valve such as a tricuspid valve that separates the right atrium.
- the connective tissue-forming substrate and production method according to the present invention are not limited to the artificial valve 1 as long as it is a membranous connective tissue, and can produce anything such as an artificial blood vessel and an artificial cornea. .
- a protrusion is formed on the connective tissue You may make it form the protrusion formation groove
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Abstract
Description
まず、本実施形態の結合組織体形成用基材及び生産方法を用いて生産する膜状の結合組織体としての人工弁について説明する。
基材19の弁体形成部21の基端側の嵌合穴に円形突起26を嵌合させて、弁体形成部21の基端側にフランジ24を取り付け、基材19を組み立てる。これにより、切欠23の基端側がフランジ24で塞がれて溝部25が構成される(図6(a)、(b))。
基材表面に切断線形成用溝28を有する基材19を生体組織材料の存在する環境下へ置く(図6(b))。生体組織材料の存在する環境下とは、動物の生体内(例えば、皮下や腹腔内への埋入)、又は、動物の生体外において生体組織材料が浮遊する溶液中等の人工環境内が挙げられる。生体組織材料としては、ヒト、イヌ、ウシ、ブタ、ヤギ、ウサギ、ヒツジなどの他の哺乳類動物由来のものや、鳥類、魚類、その他の動物由来のもの、又は人工材料を用いることもできる。
設置工程の後、所定時間が経過することにより、基材19の周囲に膜状の結合組織30が形成される(図6(c))。結合組織30は、溝部25に侵入し、増厚された止着部6を形成する。
所定時間の形成工程を経て、結合組織30が十分に形成された後、基材19を生体組織材料の存在する環境下から取り出す取り出し工程を行う。生体組織材料の存在する環境下から取り出された基材19は、その両端面を含む表面の全体を結合組織30による膜で覆われている。
基材19の両端部の表面の結合組織30を除去し(図6(d))、その後、弁体形成部21の基端側からフランジ24を取り外して、止着部6が嵌ったままの溝部25の基端側を開放し、基材19の周面を覆っている残りの結合組織30を、基材19の表面から筒状の結合組織体20として剥離して取り出す(図6(e))。
増厚溝29によって形成された突条を目印として、結合組織体20のコーナー部の位置を把握しつつ切断線31を見つけ、この切断線31に沿って結合組織体20を切断して紐状の腱索7を形成し、これにより、弁体5から腱索7を延設した人工弁1が得られる(図6(f))。この切断工程において、切断線31を構成する突条を残すように切断した場合には、残した突条によって切断縁を補強する効果が期待できる。
本実施形態は、第1実施形態とほぼ同じ構成であるが、図7に示すように、結合組織体形成用基材として、基端断面が円形で先端断面が正方形の基材19に代えて、扁平形状の基材32を採用したものである。
本実施形態は、第2実施形態とほぼ同じ構成であるが、人工弁の止着部を増厚することなく、止着部を他の部位と同程度の厚さに形成するものである。本実施形態では、図8に示すように、基材19、32に代えて、弁体形成部33の基端部に溝部25を有しない基材38を用いて人工弁を形成する。
本実施形態は、第1実施形態~第3実施形態とほぼ同じ構成であるが、一端を折り返した構造の人工弁41を生産するものである。
基材47を生体組織材料の存在する環境下へ置く(図11(a))。
設置工程の後、所定時間が経過することにより、基材47の周囲に膜状の結合組織50が形成されると共に、折返し目印形成溝48及び止着目印形成溝49に結合組織50が侵入して折返し目印48a及び止着目印49aが形成される(図11(b))。
所定時間の形成工程を経て、結合組織50が十分に形成された後、基材47を生体組織材料の存在する環境下から取り出す取り出し工程を行う。生体組織材料の存在する環境下から取り出された基材47は、その両端面を含む表面の全体を結合組織50による膜で覆われている。
基材47の両端部の表面の結合組織50を除去した後、基材47の周面を覆っている残りの結合組織50を、基材47の表面から、折返し目印48a及び止着目印49aを有する管状の結合組織体51として剥離して取り出す(図11(c))。
折返し目印48aの位置を折返し部45として、管状の結合組織体51の一端を内側に折り返し、外側部分を外管部42とすると共に、内側に折り返した部分を弁体43とすることにより、外管部42の内側に筒状の弁体43を形成する(図11(d))。
波形の止着目印49aに沿って、外管部42の内側に折り返した弁体43を外管部42の内面に止着し、波形の止着部46を構成する。これにより、弁体43が止着部46の1波分を支持部とする複数の弁葉44を構成し、外管部42の内側に複数の弁葉44を設けてなる人工弁41が得られる(図11(e))。
2 心臓
3 左室
4 左房
5 弁体
6 止着部
7 腱索
8 中央穴
13 腱索先端部
14 前尖
15 後尖
16 右室
17 大動脈
18 大動脈弁
19 基材
20 結合組織体
21 弁体形成部
22 腱索形成部
23 切欠
24 フランジ
25 溝部
26 円形突起
27 ツマミ
28 切断線形成溝
29 増厚溝
30 結合組織
31 切断線
32 基材(第2実施形態)
33 弁体形成部
34 腱索形成部
35 切断線形成溝
36 増厚溝
38 基材(第3実施形態)
39a、39b、39c、39d、39e 弁体用切断線形成溝
40 切断線形成溝
40a、40b、40c、40d、40e 分岐溝
41 人工弁(第4実施形態)
42 外管部
43 弁体
44 弁葉
45 折返部
46 止着部
47 基材
48 折返し目印形成溝
48a 折返し目印
49 止着目印形成溝
49a 止着目印
50 結合組織
51 結合組織体
X 流路
Claims (9)
- 生体組織材料の存在する環境下におくことにより、その表面に膜状の結合組織体を形成するための基材であって、基材表面に、前記結合組織体を加工する際の目印を形成する加工目印形成部が形成されたことを特徴とする結合組織体形成用基材。
- 前記加工目印形成部として、前記結合組織体を切断加工する際の切断線を形成する切断線形成溝が形成されたことを特徴とする請求項1に記載の結合組織体形成用基材。
- 前記加工目印形成部として、前記結合組織体を折返し加工する際の折返し目印を形成する折返し目印形成部が形成されたことを特徴とする請求項1又は2に記載の結合組織体形成用基材。
- 前記加工目印形成部として、前記結合組織体を止着加工する際の止着目印を形成する止着目印形成部が形成されたことを特徴とする請求項1、2又は3に記載の結合組織体形成用基材。
- 前記基材表面に、結合組織体に突条を形成する突条形成溝が前記加工目印形成部とは別に形成されたことを特徴とする請求項1~4のいずれかに記載の結合組織体形成用基材。
- 前記基材表面に、結合組織体に突条を形成する突条形成溝が前記切断線形成溝とは別に形成され、
前記突条形成溝は、切断線形成溝と溝幅方向に並設されたことを特徴とする請求項2に記載の結合組織体形成用基材。 - 前記突条形成溝は、結合組織体を増厚補強する増厚溝とされたことを特徴とする請求項5又は6に記載の結合組織体形成用基材。
- 結合組織からなる膜状の結合組織体を生産する方法であって、
基材表面に切断線形成用溝を有する基材を生体組織材料の存在する環境下におく設置工程と、前記基材の周囲に結合組織を形成しつつ該結合組織を前記切断線形成用溝に侵入させて切断線を形成する形成工程と、前記環境下から結合組織で被覆された前記基材を取り出す取り出し工程と、前記基材表面を覆う結合組織を膜状の結合組織体として剥離して取り出す分離工程と、前記結合組織体を切断線に沿って切断する切断工程と、を備えたことを特徴とする結合組織体の生産方法。 - 結合組織からなる膜状の結合組織体を生産する方法であって、
基材表面に加工目印形成部を有する基材を生体組織材料の存在する環境下におく設置工程と、前記基材の周囲に結合組織を形成しつつ該結合組織を前記加工目印形成部に侵入させて目印を形成する形成工程と、前記環境下から結合組織で被覆された前記基材を取り出す取り出し工程と、前記基材表面を覆う結合組織を膜状の結合組織体として剥離して取り出す分離工程と、前記結合組織体を前記目印の位置で加工する加工工程と、を備えたことを特徴とする結合組織体の生産方法。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006314601A (ja) * | 2005-05-13 | 2006-11-24 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2007037763A (ja) | 2005-08-03 | 2007-02-15 | National Cardiovascular Center | 人工弁を有するステント |
JP2007312821A (ja) | 2006-05-23 | 2007-12-06 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2008237896A (ja) | 2007-02-26 | 2008-10-09 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2010088625A (ja) * | 2008-10-07 | 2010-04-22 | National Cardiovascular Center | 人工弁 |
JP2010094476A (ja) | 2008-10-15 | 2010-04-30 | Shinkan Kogyo Kk | 結合組織体形成用基材およびそれを用いた結合組織体の製造方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6666886B1 (en) * | 1999-02-16 | 2003-12-23 | Regents Of The University Of Minnesota | Tissue equivalent approach to a tissue-engineered cardiovascular valve |
WO2005011534A1 (en) * | 2003-07-31 | 2005-02-10 | Cook Incorporated | Prosthetic valve devices and methods of making such devices |
WO2009156471A1 (en) * | 2008-06-26 | 2009-12-30 | Iberhospitex, S.A. | Prosthetic heart valve and method for making such a valve |
US8685082B2 (en) * | 2010-11-18 | 2014-04-01 | National Cerebral And Cardiovascular Center | Base material for forming valved lumen shape tissue, method for producing valved lumen shape tissue, and valved artificial blood vessel |
JP6010018B2 (ja) * | 2011-09-09 | 2016-10-19 | 新幹工業株式会社 | 弁付きステント、弁付きステント形成用基材、及び弁付きステントの生産方法 |
-
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- 2014-08-22 WO PCT/JP2014/071985 patent/WO2015029891A1/ja active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006314601A (ja) * | 2005-05-13 | 2006-11-24 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2007037763A (ja) | 2005-08-03 | 2007-02-15 | National Cardiovascular Center | 人工弁を有するステント |
JP2007312821A (ja) | 2006-05-23 | 2007-12-06 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2008237896A (ja) | 2007-02-26 | 2008-10-09 | National Cardiovascular Center | 結合組織体形成基材およびそれを用いた結合組織体の製造方法 |
JP2010088625A (ja) * | 2008-10-07 | 2010-04-22 | National Cardiovascular Center | 人工弁 |
JP2010094476A (ja) | 2008-10-15 | 2010-04-30 | Shinkan Kogyo Kk | 結合組織体形成用基材およびそれを用いた結合組織体の製造方法 |
Non-Patent Citations (1)
Title |
---|
See also references of EP3040053A4 |
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