US20130178929A1 - Valved stent, base material for forming valved stent, and method for producing valved stent - Google Patents

Abstract

The present invention provides a valved stent that can provide a valve function without blocking a branch blood vessel, and also can provide a valve function with minimum covering of blood vessel tissue in a stent indwelling section. Specifically, a cylindrical stent body4 is provided. A leaflet5 that can open/close a blood vessel2 in a blood flow direction is provided. The leaflet5 is composed of connective tissue and protrudes radially inward from the stent body4. An inside and an outside of the stent body4 radially communicate with each other. The stent does not block a branch blood vessel8. An area of the blood vessel covered with the stent is reduced.

Description

TECHNICAL FIELD
• The present invention relates to a valved stent indwelled in a blood vessel to provide a valve function to the blood vessel, a base material for forming the valved stent, and a method for producing the valved stent.
BACKGROUND ART
• Many studies have been made on regenerative medicine for regenerating cells, tissue, or organs damaged by diseases or accidents with artificial materials or cells. Normally, it is known that a body has a self-protective function, and when foreign matter such as a thorn enters a shallow position in the body, the body tries to force the foreign matter out of the body, while when foreign matter enters a deep position in the body, fibroblasts aggregate around the foreign matter, and a capsule of connective tissue mainly composed of fibroblasts and collagen is formed to cover the foreign matter, thereby isolating the foreign matter in the body. A plurality of methods are reported in which using the latter self-protective reaction, tubular tissue derived from a living body with living cells in a living body is formed (seePatent Literatures 1 to 3).
• Patent Literature 4 discloses a stent in which, for example, a mesh-like tubular biocompatible stent body of metal is entirely covered with a connective tissue layer, and an artificial valve is formed integrally with the connective tissue layer. The stent is covered with a connective tissue film formed in a living body, and the tissue film is rich in matrix such as collagen, thereby allowing vascular endothelium to be rapidly organized and reconstructed.
CITATION LISTPatent Literature
• Patent Literature 1: Japanese Patent Laid-Open No. 2007-312821
• Patent Literature 2: Japanese Patent Laid-Open No. 2008-237896
• Patent Literature 3: Japanese Patent Laid-Open No. 2010-094476
• Patent Literature 4: Japanese Patent Laid-Open No. 2007-037763 (claim 1, paragraphs 0029, 0037 to 0039)
SUMMARY OF INVENTIONTechnical Problem
• Some blood vessels such as an aortic sinus (sinus of Valsalva) of an aorta include an ampulla with a blood vessel wall expanding radially outward, and a plurality of leaflets that protrude radially inward are opened/closed in a blood flow direction inside and on an upstream side of the ampulla. The ampulla functions as an escape path for blood when a valve is opened, and functions as a reservoir for the blood when the valve is closed, thereby facilitating opening/closing of the valve and preventing backflow of the blood.
• There is a need for an artificial valve provided in such an ampulla of the blood vessel, and it is considered that the stent inPatent Literature 4 is indwelled in the ampulla to provide a valve function.
• However, a coronary artery having an influence on a heart branches off from an aortic sinus of an aorta, and when the stent inPatent Literature 4 is indwelled in the aortic sinus as an aortic valve, the connective tissue layer covering the entire stent may block the coronary artery to cause myocardial infarction.
• On the other hand, the stent inPatent Literature 4 is covered with a connective tissue film, and thus the vascular endothelium can be rapidly organized and reconstructed. However, in some cases, the connective tissue film covering the stent body may cover blood vessel tissue in a stent indwelling section to increase risk of a blood clot in a blood vessel and retard healing.
• The present invention has an object to provide a valved stent that can provide a valve function without blocking a branching blood vessel and that can also provide a valve function with minimum covering of blood vessel tissue in a stent indwelling section, a base material for forming the valved stent, and a method for producing the valved stent.
Solution to Problem
• To achieve the object, the present invention provides a valved stent indwelled in a blood vessel to provide a valve function to the blood vessel, including: a cylindrical stent body; and a leaflet composed of connective tissue that protrudes radially inward from the stent body and is capable of opening/closing the blood vessel in a blood flow direction, wherein an inside and an outside of the stent body radially communicate with each other.
• According to the above described configuration, the inside and the outside of the stent body radially communicate with each other, and thus even if the stent is indwelled in an aortic sinus of an aorta or the like from which a coronary artery branches off, an artificial valve as an aortic valve can be provided to provide a valve function without blocking the branch blood vessel by the stent, for example. Also, because the inside and the outside of the stent body radially communicate with each other, an area of the blood vessel covered with the stent can be minimized to leave the blood vessel tissue in the stent indwelling section substantially intact. This allows an artificial valve to be provided in an aorta or a pulmonary artery, and also reduces risk of a blood clot and facilitates healing.
• As the stent body, a mesh-like metal member can be exemplified. This configuration can provide sufficient strength of the stent, also minimize an area where communication between the inside and the outside of the stent body is prevented, and further easily increases a diameter of the stent body to a desired diameter. The stent body may be any member such as a synthetic resin cylinder having a communication hole, and is not limited to the mesh-like metal member, as long as the inside and the outside of the stent body communicate with each other.
• The stent may be indwelled in an ampulla with a blood vessel wall of the blood vessel expanding radially outward, and the stent body may be set to a length such that the stent body can span the ampulla in a blood flow direction and be held on opposite sides. According to this configuration, the stent can span the ampulla of the blood vessel and be held on the opposite sides, thereby allowing a linear stent to be indwelled in the ampulla with a gap between the blood vessel wall of the ampulla and the stent. When the artificial valve is closed, the blood in the stent once flows through a wide range of the cylindrical wall of the stent into the gap between the blood vessel wall of the ampulla and the stent, and flows from the gap to the branch blood vessel, thereby allowing the blood to be smoothly fed to the branch blood vessel.
• A plurality of leaflets may be arranged in parallel in a circumferential direction of the stent body, and the plurality of leaflets may be integrated at its base end. According to this configuration, the plurality of leaflets are arranged in the circumferential direction, and also the leaflets are integrated at the base end to constitute an artificial valve. This provides substantially the same configuration as an aortic valve or a pulmonary valve constituted by a trileaflet valve.
• A contact section that covers the stent body and that comes into contact with the blood vessel wall may be composed of connective tissue, and a plurality of the contact sections may be continuously formed in the blood flow direction at intervals in the circumferential direction of the stent body to expose the stent body between the plurality of contact sections.
• According to this configuration, the contact section is formed of the connective tissue, thereby preventing the stent body from coming into direct contact with the blood vessel wall as foreign matter. Also, the stent body is exposed between the plurality of contact sections, thereby providing communication between the inside and the outside of the stent body at the respective exposed portions of the stent body. A structure in which a leaflet is simply provided in the stent body may be used without the contact section being formed of the connective tissue. In this case, for example, the stent body may be made of biocompatible metal such as stainless, titanium, tantalum, aluminum, tungsten, nickel-titanium alloy, cobalt chrome alloy, or titanium-aluminum-vanadium alloy; biodegradable magnesium alloy; or hydrolyzable polymer such as polylactic acid.
• The contact section may be formed so as to be aligned with a boundary between the plurality of leaflets in the circumferential direction of the stent body. According to this configuration, the opposite ends of the leaflet can be continuous with the contact sections, and the leaflet can be firmly integrated with the stent body in three positions at the base end and the opposite sides. Further, the exposed section that provides communication between the inside and the outside of the stent can be circumferentially aligned with the leaflet. This provides substantially the same configuration as the aortic valve or the pulmonary valve in which the leaflet is circumferentially aligned with the branch blood vessel.
• The present invention also provides a base material for forming a valved stent that is placed in an environment with a body tissue material to form film-like tissue on a surface of the base material and form a valved stent including a leaflet protruding radially inward from a stent body, including: a columnar base material body; a plurality of recesses formed in an outer peripheral surface of the base material body; an inner cover that covers the recesses to form a leaflet forming space for forming the leaflet; and an outer cover placed on an outer surface side of the inner cover with the stent body interposed therebetween.
• According to the above-described configuration, the recesses in the base material body are covered with the inner cover to form the leaflet forming space. Thus, when the film-like tissue is formed on the surface of the base material, the tissue may enter the leaflet forming space to form the leaflet, and also each leaflet forming section forms each leaflet, thereby eliminating the need to cut the leaflet. Further, the outer cover is placed on the outer surface side of the inner cover with the stent body interposed therebetween. This prevents the tissue from being formed in a region of the stent body between the inner cover and the outer cover, and can form an exposed portion that provides communication between the inside and the outside of the stent body, and the inner cover can also serve as a member for forming the leaflet and the exposed portion. The leaflet may be integrated with the stent body in a region where the tissue enters the leaflet forming space.
• In the present invention, the “body tissue material” is a material required for forming desired tissue derived from a living body, and includes, for example, animal cells such as fibroblasts, smooth muscle cells, endothelial cells, stem cells, ES cells, or iPS cells, various proteins (collagen or elastin), saccharides such as hyaluronic acid, and other cells, cell growth factors, or various physiologically active substances in the living body such as cytokine. The “body tissue material” includes materials derived from mammals such as humans, dogs, cows, pigs, goats or sheep, or from birds, fish, and other animals, and artificial materials comparable thereto.
• Also, “in the environment with a body tissue material” refers to an inside of a living body (for example, embedding under skin of four limbs, lumber, back, or abdomen, or into abdominal cavity) of animals (mammals such humans, dogs, cows, pigs, goats or sheep, or birds, fish, and other animals) or to an artificial environment containing a body tissue material outside a living body of animals. Embedding into animals is preferably performed by a less invasive method with a minimum incision under sufficient anesthesia in a spirit of animal protection.
• The inner cover and the outer cover preferably have open sections that expose a boundary between the plurality of recesses in the outer peripheral surface of the base material body via the stent body. According to this configuration, the inner cover and the outer cover have the open sections. Thus, tissue that covers the stent body is formed on a surface of the boundary between the recesses in the base material body to be a contact section that comes into contact with the blood vessel wall, the opposite sides of the leaflet can be continuous with the contact section, and the leaflet can be firmly integrated with the stent body in three positions at the base end and the opposite sides. Further, the recesses in the base material body are covered with the inner cover and the outer cover, and thus the inner cover and the outer cover can hold the stent body therebetween to form the exposed portion, and the exposed portion of the stent body is circumferentially aligned with the leaflet to provide substantially the same configuration as the aortic valve and the pulmonary valve.
• A positioning section that circumferentially positions the base material body, the inner cover, and the outer cover is preferably provided. According to this configuration, the base material body, the inner cover, and the outer cover can be positioned, thereby preventing misalignment thereof, and ensuring formation of the leaflet and the exposed portion of the stent body.
• The present invention provides a method for producing a valved stent including: an assembly step of assembling a base material for forming the valved stent described above by incorporating a stent body between an inner cover and an outer cover; a placement step of placing the base material for forming the valved stent in an environment with a body tissue material; a formation step of forming film-like tissue around the base material for forming the valved stent; a taking-out step of taking out the base material for forming the valved stent covered with tissue from the environment; and a separation step of integrally delaminating and taking out tissue including the leaflet and the stent body from the base material for forming the valved stent as a valved stent, wherein the separation step is a step of removing tissue on surfaces of opposite ends of the base material for forming the valved stent and the outer cover, detaching the outer cover, and then central-axially disassembling and taking out the base material body and the inner cover from a lumen of the valved stent. In the present invention, for the transplant recipient, any of autologous transplantation, allotransplantation, and heterotransplantation may be performed, but autologous transplantation or allotransplantation is preferable in order to prevent rejection. For the heterotransplantation, elimination of immunogen such as known decellularization is preferably performed in order to avoid rejection.
• The present invention provides a base material for forming a valved stent that is placed in an environment with a body tissue material to form film-like tissue on a surface of the base material and form a reverse valved stent with an inside and an outside being reversed of a valved stent including a leaflet protruding radially inward from a stent body, including: a columnar base material body; and a base material cover placed on an outer peripheral side of the base material body with the stent body interposed therebetween.
• According to the above-described configuration, the base material cover is placed on the outer peripheral side of the base material body with the stent body interposed therebetween. Thus, the film-like tissue is formed on the surface of the base material, and the leaflet can be formed on the outer surface of the base material cover outside the stent body. Thus, the reverse valved stent having the leaflet on the outer peripheral side of the stent body can be formed without covering the stent body with tissue, and the reverse valved stent can be reversed to obtain a valved stent.
• Further, when the reverse valved stent is formed, the leaflet is formed on the outer surface of the base material cover placed on the outer peripheral side. This eliminates the need to form the leaflet by causing the tissue to enter deep into a narrow space, and allows a thin leaflet to be reliably formed in a short time. The leaflet may be integrated with the stent body via tissue formed in a region where the base material body is exposed from the base material cover, or tissue slightly entering a gap between the base material cover and the base material body.
• The base material cover preferably has an open section that exposes the outer peripheral surface of the base material body via the stent body. According to this configuration, the base material cover has the open section, and thus tissue covering a part of the stent body can be formed on the surface of the base material body, and the leaflet and the stent body can be integrated via the tissue.
• Further, the outer peripheral surface of the base material body may have an entry groove that connective tissue enters, and the base material cover may be placed so that the entry groove is aligned with the open section. According to this configuration, the tissue enters the entry groove to cover a part of the stent body from the inside and the outside. Thus, the leaflet and the stent body can be more firmly integrated via the tissue.
• The base material cover may have a bulge formed by expanding an outer surface side. According to this configuration, the leaflet can be expanded to an enough size to more reliably prevent backflow of blood or the like. Further, the base material cover has the bulge, and thus thin tissue with a sufficient modulus of elasticity can be formed on the surface of the base material cover.
• The present invention provides a method for producing a valved stent including: an assembly step of assembling a base material for forming the valved stent described above by incorporating a stent body between a base material body and a base material cover; a placement step of placing the base material for forming the valved stent in an environment with a body tissue material; a formation step of forming film-like tissue around the base material for forming the valved stent; a taking-out step of taking out the base material for forming the valved stent covered with tissue from the environment; and a separation step of integrally delaminating and taking out tissue including the leaflet and the stent body from the base material for forming the valved stent as a reverse valved stent, wherein the separation step is a step of removing tissue on opposite ends of the base material for forming the valved stent, then central-axially disassembling the base material body and the base material cover, taking out the base material cover from between the leaflet and the stent body, and taking out the base material body from a lumen of the reverse valved stent, and the method further includes, after the separation step, a reverse step of reversing an inside and an outside of the reverse valved stent to form a valved stent.
Advantageous Effects of Invention
• As described above, according to the present invention, the inside and the outside of the stent body radially communicate with each other, thereby providing a valve function to an aortic sinus or the like without blocking a branch blood vessel such as a coronary artery. Further, the communication of the stent body can minimize an area of the blood vessel covered with the stent to leave the blood vessel tissue in the stent indwelling section substantially intact. This provides a valve function to an aorta or a pulmonary artery, and also reduces risk of a blood clot and facilitates healing.
BRIEF DESCRIPTION OF DRAWINGS
• FIG. 1 is a perspective view of a valved stent according to the present invention.
• FIG. 2 is a plan view of the valved stent.
• FIG. 3 is an A-A sectional view ofFIG. 2, showing a valve being opened.
• FIG. 4 is an A-A sectional view ofFIG. 2, showing a valve being closed.
• FIG. 5 is a perspective view of a stent body.
• FIG. 6 is a vertical sectional view of the valved stent indwelled in an ampulla of a blood vessel.
• FIG. 7 is a B-B sectional view ofFIG. 6.
• FIG. 8 is a C-C sectional view ofFIG. 6.
• FIG. 9 is a perspective view of a base material for forming a valved stent (first embodiment).
• FIG. 10 is a vertical sectional view of the base material for forming a valved stent (first embodiment).
• FIG. 11 is a perspective view of a base material body (first embodiment).
• FIG. 12 is a perspective view of an inner cover (first embodiment).
• FIG. 13 is a perspective view of an outer cover (first embodiment).
• FIG. 14 illustrates a procedure for assembling the base material for forming a valved stent (first embodiment).
• FIG. 15 illustrates a procedure for forming the valved stent (first embodiment).
• FIG. 16 is a perspective view of a base material for forming a valved stent (second embodiment).
• FIG. 17 is a perspective view of a base material body (second embodiment).
• FIG. 18 is a perspective view of a base material cover (second embodiment).
• FIG. 19 is a photograph illustrating a procedure for forming the valved stent (second embodiment).
• FIG. 20 is a perspective view of a base material for forming a valved stent (third embodiment).
• FIG. 21 is a perspective view of a base material body (third embodiment).
• FIG. 22 is a perspective view of a base material cover (third embodiment).
• FIG. 23 is a perspective view of a base material for forming a valved stent (fourth embodiment).
• FIG. 24 is a perspective view of a base material body (fourth embodiment).
• FIG. 25 is a perspective view of a base material cover (fourth embodiment).
• FIG. 26 is a photograph of a section of tissue (expansion height of 0 mm).
• FIG. 27 is a photograph of a section of tissue (expansion height of 2 mm).
• FIG. 28 is a photograph of a section of tissue (expansion height of 3 mm).
• FIG. 29 is a perspective view of a base material for forming a valved stent (fifth embodiment).
• FIG. 30 is a perspective view of a base material body (fifth embodiment).
• FIG. 31 is a perspective view of a base material cover (fifth embodiment).
DESCRIPTION OF EMBODIMENTS
• Now, first to fifth embodiments of a valved stent, a base material for forming a valved stent, and a method for producing the valved stent according to the present invention will be described with reference to the drawings.
First Embodiment
• As shown inFIGS. 1 to 8, avalved stent1 is, for example, indwelled in anampulla3 of ablood vessel2 having a blood vessel wall expanding radially outward, such as an aortic sinus of an aorta, to provide a valve function to theblood vessel2, and includes acylindrical stent body4, aleaflet5 composed of connective tissue that protrudes radially inward from thestent body4 and is capable of opening/closing theblood vessel2 in a blood flow direction, and acontact section6 composed of connective tissue that covers thestent body4 and comes into contact with the blood vessel wall.
• Thestent body4 is a mesh-like metal member, for example, with thin metal wires arranged in a diagonal grid pattern, an inside and an outside of thestent body4 radially communicating with each other at an exposedportion7 between a plurality ofsuch contact sections6, and is set to a length such that thestent body4 can span theampulla3 in the blood flow direction and be held on opposite sides. Thestent body4 is preferably made of biocompatible metal such as stainless, titanium, tantalum, aluminum, tungsten, nickel-titanium alloy, cobalt chrome alloy, titanium-aluminum-vanadium alloy; biodegradable magnesium alloy; or hydrolyzable polymer such as polylactic acid.
• As shown inFIGS. 6 to 8, the inside and the outside of thestent body4 communicate with each other at the exposedportion7, and thus thestent body4 can be indwelled in theampulla3 without blocking abranch blood vessel8 such as a coronary artery branching off from an aortic sinus, and also an area of the blood vessel wall of theblood vessel2 covered with thestent body4 is minimized. Thestent body4 spans theampulla3 in the blood flow direction, and thus agap9 is created between the blood vessel wall of theampulla3 and thevalved stent1. When the valve is closed, blood once flows from a wide range of the exposedportion7 into thegap9, and then flows into thebranch blood vessel8. This allows the blood in thevalved stent1 to smoothly flow into thebranch blood vessel8, and eliminates the need to accurately align the exposedportion7 with thebranch blood vessel8.
• A plurality ofsuch leaflets5 are arranged in parallel in a circumferential direction of thestent body4, and reciprocate radially inward and outward to function as, for example, an aortic valve having theleaflets5 that are trileaflet valves and open/close an aorta in the blood flow direction. The plurality ofleaflets5 are integrated at its base end to constitute an annularleaflet base end10, and theleaflet base end10 is formed to cover around one end of thestent body4. Further, opposite sides of eachleaflet5 are secured to thestent body4 via theconnection section6, and the plurality ofleaflets5 are each integrated with thestent body4 in three positions at the base end and the opposite sides. InFIG. 2, dash-double-dot lines are phantom lines showing theleaflets5 being closed.
• Thecontact section6 is formed continuously in the blood flow direction from theleaflet base end10 around one end of thestent body4 to around the other end of thestent body4. A plurality ofsuch contact sections6 are formed at intervals in the circumferential direction of thestent body4 so as to be aligned with a boundary between the plurality ofleaflets5 in the circumferential direction of thestent body4, and opposite sides of theleaflet5 are continuous with eachcontact section6. Between the plurality ofcontact sections6, the exposedportion7 is provided so as to expose thestent body4 to provide communication between the inside and the outside of thestent body4.
• Next, abase material11 for forming avalved stent11 for forming the above-describedvalved stent1 will be described.
• As shown inFIGS. 9 to 13, the base material for forming avalved stent11 is placed in an environment with a body tissue material to form film-like tissue on a surface of the base material and form thevalved stent1, and includes a columnarbase material body12, a plurality ofrecesses13 formed in an outer peripheral surface of thebase material body12, aninner cover15 that covers therecesses13 to form aleaflet forming space14 for forming theleaflet5, and anouter cover16 placed on an outer surface side of theinner cover15 with thestent body4 interposed therebetween.
• Thebase material body12 includes acylinder18 having the plurality ofrecesses13 formed in the peripheral surface and a disk-like flange17 having a larger diameter than thecylinder18, and is generally formed into a columnar shape with theflange17 being provided at one end of thecylinder18. Asmall diameter portion18aand a plurality ofsuch protrusions19 are formed at a front end of thecylinder18, and thesmall diameter portion18aand theprotrusions19 are engaged with aflange20 of theinner cover15 to mount theinner cover15. Theflange17 has anair hole21 through which air escapes from or to the inside of thecylinder18 when theinner cover15 is attached or detached.
• The material for thebase material body12 is preferably resin that has strength (hardness) such as not to be significantly deformed when embedded into a living body, has chemical stability and resistance to load such as sterilization, and contains no or little eluate that stimulates the living body, for example, silicone resin or acrylic resin can be mentioned, but is not limited to these. A thickness of thevalved stent1 is determined by the outer diameter of thecylinder18, and thus the diameter can be changed depending on a desired thickness.
• Therecesses13 are set to a depth such that a cylindrical surface including bottom surfaces thereof has a slightly larger diameter than thesmall diameter portion18a, and formed with substantiallytriangular boundaries22 therebetween in the circumferential direction in a plurality of positions of thecylinder18 over the entire length except thesmall diameter portion18a. Ataper23 is formed in therecess13 near theflange17 so that the connective tissue can easily enter theleaflet forming space14 when theleaflet5 is formed.
• Theinner cover15 is made of, for example, acrylic resin, and includes a plurality of substantiallysemielliptical cover pieces24 and aflange20 having substantially the same diameter as thecylinder18 of thebase material body12, and thecover pieces24 protrude from a peripheral edge of theflange20 toward one surface.
• Thecover piece24 covers therecess13 of thebase material body12 except the peripheral edge to form theleaflet forming space14, and forms an entry opening through which the connective tissue enters theleaflet forming space14 near thetaper23. A front end surface of theleaflet forming space14 is formed by one surface and the peripheral edge of theflange20, and agroove25 forming a front end shape of theleaflet5 is formed in the one surface and the peripheral edge of theflange20.
• Anopen section26 that exposes theboundary22 of thebase material body12 is formed betweencover pieces24 adjacent to each other, and theboundary22 and the outer surfaces of thecover pieces24 are included in a common cylindrical surface.
• At a center of one surface of theflange20, afitting recess27 in which thesmall diameter portion18aof thecylinder18 of thebase material body12 fits, and afitting hole28 in which theprotrusion19 fits are formed. Thesmall diameter portion18aand thefitting recess27 constitute a radial positioning section that radially positions theinner cover15 with respect to thebase material body12. Theprotrusion19 and thefitting hole28 constitute a circumferential positioning section that circumferentially positions theinner cover15 with respect to thebase material body12.
• At a center of the other surface of theflange20, afitting shaft29 is formed to protrude, and a plurality ofprotrusions30 are formed around a base end of thefitting shaft29 so that thefitting shaft29 and theprotrusion30 are engaged with theouter cover16 to mount theouter cover16 to theinner cover15.
• Theouter cover16 is made of, for example, acrylic resin, and includes a plurality of substantiallysemielliptical cover pieces31, acylinder32 having substantially the same diameter as theflange17 of thebase material body12 and covering an outer peripheral side of theflange20 of theinner cover15, and aflange33 having substantially the same diameter as theflange17 of thebase material body12. In theouter cover16, thecylinder32 protrudes from a peripheral edge of theflange33 toward one side, and further thecover piece31 protrudes from one end of thecylinder32.
• Thecover piece31 has substantially the same shape as thecover piece24 of theinner cover15, and covers the outer surface of thecover piece24 via thestent body4. Thecover piece31 prevents the connective tissue from entering between thecover piece31 and thecover piece24 of theinner cover15, and forms the exposedportion7 in a region of thestent body4 between thecover pieces24 and31.
• Anopen section34 that exposes theboundary22 of thebase material body12 is formed betweencover pieces31 adjacent to each other. Theopen sections26 and34 of theinner cover15 and theouter cover16 expose theboundary22 of thebase material body12 via thestent body4, and allow the connective tissue to enter the outer surface side of theboundary22 to form thecontact section6 of thevalved stent1.
• At a center of theflange33, afitting bore35 in which thefitting shaft29 of theinner cover15 fits is formed, andfitting holes36 in which theprotrusions30 of theinner cover15 fit are formed around the fitting bore35. Thefitting shaft29 and the fitting bore35 constitute a radial positioning section that radially positions theouter cover16 with respect to theinner cover15. Theprotrusions30 and the fitting holes36 constitute a circumferential positioning section that circumferentially positions theouter cover16 with respect to theinner cover15.
• Next, a method for producing thevalved stent1 using the above-described base material for forming avalved stent11 will be described.
• This production method includes: an “assembly step” of assembling the base material for forming avalved stent11 by incorporating thestent body4 between theinner cover15 and theouter cover16; a “placement step” of placing the base material for forming avalved stent11 in an environment with a body tissue material; a “formation step” of forming film-like tissue37 around the base material for forming avalved stent11; a “taking-out step” of taking out thebase material11 for forming a valved stent covered with thetissue37 from the environment; and a “separation step” of integrally delaminating and taking out thetissue37 including theleaflet5 and thestent body4 from thebase material11 for forming a valved stent as thevalved stent1.
<Assembly Step>
• Theinner cover15 is central-axially placed over thebase material body12, thesmall diameter portion18aand theprotrusion19 at the front end of thebase material body12 are fitted in thefitting recess27 and thefitting hole28 of theinner cover15 to mount theinner cover15 to the base material body12 (FIGS. 14(a) and (b)). Thus, theinner cover15 is radially and circumferentially positioned with respect to thebase material body12, and therecess13 in thebase material body12 is covered with thecover piece24 of theinner cover15 to form theleaflet forming space14.
• Then, thestent body4 is placed outside the inner cover15 (FIG. 14(c)), theouter cover16 is further placed over thestent body4, thefitting shaft29 and theprotrusions30 of theinner cover15 are fitted in the fitting bore35 and the fitting holes36 in theouter cover16, and theouter cover16 is mounted to the inner cover15 (FIG. 14(d)). Thus, theouter cover16 is radially and circumferentially positioned with respect to theinner cover15, thecover piece24 of theinner cover15 is covered with thecover piece31 of theouter cover16, thecover pieces24 and31 hold thestent body4 therebetween, and theopen sections26 and34 in theinner cover15 and theouter cover16 expose theboundary22 of thebase material body12 via thestent body4.
<Placement Step>
• The base material for forming avalved stent11 is placed in an environment with a body tissue material (FIG. 15(a)). The wording “in the environment with a body tissue material” refers to an inside of a living body (for example, embedding under skin or into abdominal cavity) of animals or to an artificial environment such as a solution in which a body tissue material is suspended outside a living body of animals. The body tissue material includes materials derived from mammals such as humans, dogs, cows, pigs, goats, rabbits or sheep, or birds, fish, and other animals, and artificial materials.
• Thebase material11 for forming a valved stent is embedded into animals with a minimum incision under sufficient anesthesia, and a wound is stitched up after the embedding. Thebase material11 for forming a valved stent is preferably embedded into, for example, an abdominal cavity having a capacity that receives the base material for forming avalved stent11, or under skin of four limbs, shoulder, back, abdomen, or the like. Embedding is preferably performed by a less invasive method with a minimum incision under sufficient anesthesia in a spirit of animal protection.
• When thebase material11 for forming a valved stent is placed in the environment with a body tissue material, various cultivation conditions may be adjusted to perform cell culture in a clean environment according to a known method.
<Formation Step>
• After the placement step, a predetermined period of time passes, and then the film-like tissue37 is formed around the base material for forming a valved stent11 (FIG. 15(b)). Thetissue37 is composed of fibroblasts and extracellular matrix such as collagen.
• One part of thetissue37 enters theleaflet forming space14 through the entry opening between the front end of thecover piece24 of theinner cover15 and thetaper23 of therecess13 to form theleaflet5, and theleaflet5 is integrated with thestent body4 via thecontact section6, and theleaflet base end10 formed at the entry opening. The other part of thetissue37 covers theboundary22 exposed from theopen sections26 and34 in theinner cover15 and theouter cover16 to form thecontact section6 integrated with thestent body4, and thecontact section6 and the opposite edges of theleaflet5 are continuous between thecover piece24 and the opposite sides of therecess13.
<Taking-Out Step>
• After thetissue37 is sufficiently formed through the formation step for the predetermined period of time, the taking-out step of taking out the base material for forming avalved stent11 from the environment with a body tissue material is performed. The base material for forming avalved stent11 taken out from the environment with a body tissue material is entirely covered with a film of body tissue. However, thetissue37 does not enter between thecover pieces24 and31 of theinner cover15 and theouter cover16, and the exposedportion7 is formed in a region of thestent body4 between thecover pieces24 and31.
<Separation Step>
• Thetissue37 on the surfaces of the opposite ends of the base material for forming avalved stent11 and theouter cover16 is removed (FIG. 15(c)), theouter cover16 is detached (FIG. 15(d)), then thebase material body12 and theinner cover15 are central-axially disassembled and taken out from a lumen of thevalved stent1 to obtain the valved stent1 (FIG. 15(e)).
• For heterotransplantation of the producedvalved stent1, elimination of immunogen such as decellularization, dehydration, or fixing is preferably performed to avoid rejection after transplantation. The decellularization includes ultrasonic treatment, surfactant treatment, eluting extracellular matrix by enzyme treatment with collagenase or the like and washing, or the like. The dehydration includes washing with a water-soluble organic solvent such as methanol, ethanol, or isopropyl alcohol. The fixing includes treatment with an aldehyde compound such as glutaraldehyde or formaldehyde.
• This embodiment is not limited to the above, but changes may be made within the scope of the present invention. For example, there is no need to align the opposite ends of thestent body4 with the opposite ends of theleaflet5 and thecontact section6 as described above, but one end and/or the other end ofstent body4 may protrude from theleaflet5 and thecontact section6 in the blood flow direction. In particular, the other end of thestent body4 may protrude from the front ends of theleaflet5 and thecontact section6, thereby allowing contact with the blood vessel wall in a wide range, and causing less displacement of thevalved stent1. Further, the protruding region of thestent body4 is increased in diameter to allow thevalved stent1 to be more reliably attached to theblood vessel2.
• Thevalved stent1 is indwelled in the aortic sinus to function as an aortic valve, and may also be indwelled in a pulmonary artery to function as a pulmonary valve.
Second Embodiment
• This embodiment is substantially the same as the first embodiment, but a reversevalved stent38 with an inside and an outside being reversed of avalved stent1 is once formed, and is reversed to form thevalved stent1. First, a base material for forming avalved stent39 will be described.
• As shown inFIGS. 16 to 18, the base material for forming avalved stent39 is placed in an environment with a body tissue material, and thus film-like tissue37 is formed on a surface of the base material to form the reversevalved stent38, and includes a columnarbase material body40, and abase material cover41 placed on an outer peripheral side of thebase material body40 via astent body4.
• Thebase material body40 includes acylindrical cylinder43 having a plurality ofentry grooves42 parallel to a central axis formed over the entire length in its outer peripheral surface, and a disk-like base44 having substantially the same diameter as thecylinder43, and is generally formed into a columnar shape with the base44 being formed at one end of thecylinder43 via aperipheral groove45.
• Thebase material cover41 includes a plurality of substantiallysemielliptical cover pieces46, acylinder47 sized to be externally fitted to thecylinder43 of thebase material body40 via thestent body4, and aflange48 having substantially the same diameter as thecylinder47. In thebase material cover41, theflange48 is provided at one end of thecylinder47, thecover pieces46 are formed to protrude from the other end of thecylinder47, and a total length of thecover piece46 and thecylinder47 is slightly shorter than a length of thecylinder43 of thebase material body40.
• A substantially triangularopen section49 that exposes the outer peripheral surface of thebase material body40 via thestent body4 is formed between thecover pieces46 adjacent to each other, and thebase material cover41 is placed outside thebase material body40 so that theopen section49 is circumferentially aligned with theentry groove42.
• Theopen section49 exposes thestent body4 provided between thebase material body40 and thebase material cover41, and exposes theentry groove42 in thebase material body40 via thestent body4. Thus, connective tissue formed around thebase material39 for forming a valved stent forms aleaflet5 on an outer surface side of thecover piece46, enters theentry groove45 from theopen section49 through thestent body4, and is integrated with thestent body4 at the inside and the outside thereof to form acontact section6. Theentry groove45 may be formed into a substantially triangular shape to match the shape of theopen section49 so that thestent body4 and thecontact section6 are more firmly integrated in a wide range.
• Next, a method for producing thevalved stent1 using the above-described base material for forming avalved stent39 will be described.
• This production method is substantially the same as in the first embodiment, and includes an “assembly step,” a “placement step,” a “formation step,” a “taking-out step,” and a “separation step,” but the “assembly step” to the “separation step” are steps for forming the reversevalved stent38, and after the “separation step,” a “reverse step” of obtaining thevalved stent1 from the reversevalved stent38 is provided.
<Assembly Step>
• Thestent body4 is placed outside thecylinder43 of thebase material body40, and central-axially positioned so that thestent body4 does not reach theperipheral groove45 in thebase material body40, thebase material cover41 is placed over thestent body4 from the front end side of thebase material body40, and theentry groove45 in thebase material body40 is circumferentially aligned with theopen section49 of thebase material cover41. Thus, a part of thestent body4 is exposed from theopen section49, theentry groove42 is exposed via thestent body4, and thebase material39 for forming a valved stent is assembled with thestent body4 being integrated between thebase material body40 and the base material cover41 (FIG. 19(a)).
• Thestent body4 is incorporated into thebase material39 for forming a valved stent in a reversed manner, and thus when the reversevalved stent38 is reversed to obtain thevalved stent1, thestent body4 can be returned to the original state.
<Placement Step>
• As in the first embodiment, thebase material39 for forming a valved stent is placed in an environment with a body tissue material.
<Formation Step>
• As in the first embodiment, after the placement step, a predetermined period of time passes, and then film-like tissue37 is formed around thebase material39 for forming a valved stent (FIG. 19(b)).
• Thetissue37 covers the outer surface of thebase material cover41 to form theleaflet5, as well as covers a portion of thecylinder43 of thebase material body40 exposed from the front end of thecover piece46 to form aleaflet base end10, and covers the outside of thestent body4 exposed from theopen section49. Further, a part of thetissue37 enters theentry groove45 through thestent body4 to form thecontact section6 integrated with thestent body4, and theleaflet5 is integrated with thestent body4 via thecontact section6 and theleaflet base end10.
<Taking-Out Step>
• As in the first embodiment, after thetissue37 is sufficiently formed, thebase material39 for forming a valved stent covered with thetissue37 is taken out from the environment with a body tissue material.
<Separation Step>
• Thetissue37 on the surfaces of the opposite ends of thebase material39 for forming a valved stent is removed (FIG. 19(c)). At this time, thetissue37 is removed so as to expose theperipheral groove45 at one end, and thetissue37 is removed so as to form the front end of theleaflet5 into a predetermined shape at the other end.
• Then, thebase material body40 and thebase material cover41 are central-axially disassembled, thebase material cover41 is taken out from between theleaflet5 and thestent body4, and thebase material body40 is taken out from a lumen of the reversevalved stent38. Thus, thetissue37 including theleaflet5 and thestent body4 are integrally delaminated from thebase material39 for forming a valved stent to obtain the reversevalved stent38 having theleaflet5 on the outer peripheral side of the stent body4 (FIG. 19(d)).
<Reverse Step>
• The inside and the outside of the taken-out reversevalved stent38 is reversed to obtain thevalved stent1 having theleaflet5 on an inner peripheral side of the stent body4 (FIG. 19(e)). At this time, the reversevalved stent38 is appropriately cooled to reduce elasticity of thestent body4, thereby facilitating reversing of the reversevalved stent38.
• Other configurations are the same as in the first embodiment.
Third Embodiment
• This embodiment is substantially the same as the second embodiment, but instead of forming the substantially triangularopen section49 in thebase material cover41 of thebase material39 for forming a valved stent, as shown inFIGS. 20 to 22, a slit-likeopen section52 is formed in abase material cover51 of abase material50 for forming a valved stent.
• Thebase material body53 includes acylindrical cylinder55 having a plurality ofentry grooves54 parallel to a central axis formed in an outer peripheral surface, and a disk-like base56 having substantially the same diameter as thecylinder55, and is generally formed into a columnar shape with the base56 being provided at one end of thecylinder55 via aperipheral groove57. Theentry groove54 in thebase material body53 is formed in a range from theperipheral groove57 to around a center of thecylinder55. Theperipheral groove57 is wider than theperipheral groove45 in the second embodiment, thestent body4 is placed to reach theperipheral groove57, and connective tissue enters theperipheral groove57 to form aleaflet base end10.
• Thebase material cover51 has aflange59 at one end of thecylinder58, the slit-likeopen section52 is formed in a range from the other end of thecylinder58 to around the center, and theopen section52 has substantially the same size as theentry groove54. Thecylinder58 of thebase material cover51 is longer than thecylinder55 of thebase material body53, and with thecylinder58 of thebase material cover51 being placed over thecylinder55 of thebase material body53, the front end of thecylinder58 of thebase material cover51 covers a part of theperipheral groove57 of thebase material body53.
• The slit-likeopen section52 is formed instead of the substantially triangularopen section49 to reduce a force to integrate thecontact section6 formed in theopen section52 with thestent body4, but thecontact section6 hardly prevents deformation such as a reduction in diameter of thestent body4, thereby facilitating insertion of thevalved stent1 into a blood vessel or the like. Other configurations are the same as in the second embodiment.
Fourth Embodiment
• This embodiment is substantially the same as the third embodiment, but as shown inFIGS. 23 to 25, abulge62 formed by expanding its outer surface side is formed on abase material cover61 of abase material60 for forming a valved stent.
• Thebulge62 is formed between slit-likeopen sections64 in acylinder63 of thebase material cover61, and expands to have a crescent sectional shape so that outer surfaces at opposite ends in a circumferential direction match an outer surface of thecylinder63, and that an outer surface at a center in the circumferential direction protrudes radially outward from the outer surface of thecylinder63. An expansion height of thebulge62 from the outer surface of thecylinder63 is larger on a side closer to a base end in an axial direction of thebase material cover61 so as to form aleaflet5 having a more expanded shape at a position closer to a front end.
• Thebase material cover61 has thebulge62, and thus theleaflet5 can be formed into a sufficiently expanded shape, and when theleaflet5 of thevalved stent1 is closed, theleaflets5 can be brought into contact with each other in a sufficient range and reliably closed.Thin tissue37 with a sufficient modulus of elasticity is formed on the surface of thebulge62, and thus theleaflet5 of thevalved stent1 composed of thetissue37 is not drawn and damaged, and is easily opened/closed without resisting a flow.
• Next, an influence of the expansion height of thebulge62 on the tissue will be described.FIGS. 26 to 28 are photographs of a section of tissue formed on the surface of thebulge62 which were taken in such a manner that thebase material60 for forming a valved stent having a diameter of 17 mm was embedded under skin of a goat, and after one month passed, tissue formed on the surface of thebulge62 was delaminated and cut, and a section thereof was photographed. In the drawings, a range indicated by an arrow shows a thickness of the tissue used as theleaflet5.
• FIG. 26 is a photograph of a section of tissue formed on a surface of a cylinder without a bulge, and shows thick non-dense tissue being formed.FIG. 27 is a photograph of a section of tissue formed on a surface of a bulge having an expansion height of 2 mm, and shows thin dense tissue being formed.FIG. 28 is a photograph of a section of tissue formed on a surface of a bulge having an expansion height of 3 mm, and shows thinner dense tissue than the tissue inFIG. 27 being formed.
• The thickness of each tissue was measured, and was 356±105 (μm) at an expansion height of 0 mm (FIG. 26), 143±62 (μm) at an expansion height of 2 mm (FIGS. 27), and 72±34 (μm) at an expansion height of 3 mm (FIG. 28).
• The modulus of elasticity of each tissue was measured, and each of the moduli of elasticity was 2762±589 (kPa) at an expansion height of 0 mm (FIG. 26), 2055±329 (kPa) at an expansion height of 2 mm (FIG. 27), and 1908±162 (kPa) at an expansion height of 3 mm (FIG. 28). These were significantly higher than a modulus of elasticity of 494±169 (kPa) of an aorta of a goat or a modulus of elasticity of 1097±389 (kPa) of a leaflet of a goat.
• A method for measuring the modulus of elasticity will now be described. The modulus of elasticity was measured using a precision measuring system manufactured by Axiom Co., Ltd. Specifically, a rectangular sheet-like tissue was secured to a stage with a bore having a diameter of 5 mm at its center, and a cylindrical probe having a diameter of 1 mm was pressed down at its central position of the bore at a speed of 0.1 mm/s until the sample was broken. Further, a moving distance of the probe and a load on the probe during the pressing were continuously measured, and the modulus of elasticity was measured from a relationship between the moving distance of and the load on the probe.
• Each time of measurement was finished, the sample was displaced, and the measurement was repeated. A total of five times of measurements were performed, and the modulus of elasticity of each sample was calculated from an average value of the five measurements. This operation was repeated for six evaluation samples, and finally an average was calculated from an average value (n=5) of the six samples, and this value was determined as the “modulus of elasticity.”
• Also, the modulus of elasticity was calculated using Expressions (1) to (4) below, and an average value of five measurement values was calculated.
• 
  k=P/δ  (1)
• 
  G=k(1−ν)/(4r_θ)  (2)
• 
  E=2G(1+ν).  (3)
• 
  E=k(1−ν²)/(2r_θ)=P(1−ν²)/(2δr_θ)  (4)
• Characters in the above expressions represent the following:
• • ν: Poisson's ratio (calculated as 0.5)
  • r_θ: probe radius (m)
  • P: load (g)
  • δ: amount of entry of probe (m)
  • k: spring constant
  • G: modulus of elasticity in shear
  • E: modulus of elasticity (kPa)
• As described above, with higher expansion height of thebulge62, thinner tissue is formed on the surface of thebulge62, and in addition, the modulus of elasticity of the tissue is not extremely reduced, and tissue having a sufficient modulus of elasticity can be obtained as compared to the modulus of elasticity of the aorta or the leaflet of the goat. Other configurations are the same as in the third embodiment.
Fifth Embodiment
• This embodiment is substantially the same as the fourth embodiment, but as shown inFIGS. 29 to 31, alateral groove68 crossing anentry groove67 is formed in abase material body66 of abase material65 for forming a valved stent, and a lateralopen section71 crossing anopen section70 is formed in abase material cover69.
• Thelateral groove68 has substantially the same groove width and groove depth as theentry groove67, is shorter than theentry groove67, and is formed perpendicularly to theentry groove67 at an end opposite to aperipheral groove73 in a central axial direction of acylinder72 of thebase material body66.
• The lateralopen section71 has substantially the same width as theopen section70, is shorter than theopen section70, and is formed perpendicularly to theopen section70 in a region adjacent to aflange75 at a base end of acylinder74 of abase material cover69.
• With thebase material cover69 being placed over thebase material body66, thelateral groove68 overlaps the lateralopen section71, and connective tissue enters thelateral groove68 and the lateralopen section71. Thus, a T-shaped reinforcement section is formed at a front end of acontact section6 formed in theentry groove67 and theopen section70, and thecontact section6 and astent body4 are more firmly integrated. Other configurations are the same as in the fourth embodiment.
REFERENCE SIGNS LIST
• 1 Valved stent (first to fifth embodiments)
• 2 Blood vessel
• 3 Ampulla
• 4 Stent body
• 5 Leaflet
• 6 Contact section
• 7 Exposed portion
• 8 Branch blood vessel
• 10 Leaflet base end
• 11 Base material for forming a valved stent (first embodiment)
• 12 Base material body
• 13 Recess
• 14 Leaflet forming space
• 15 Inner cover
• 16 Outer cover
• 22 Boundary
• 23 Taper
• 24 Cover piece
• 26 Open section
• 31 Cover piece
• 34 Open section
• 37 Tissue
• 38 Reverse valved stent (second to fifth embodiments)
• 39 Base material for forming a valved stent (second embodiment)
• 40 Base material body
• 41 Base material cover
• 42 Entry groove
• 46 Cover piece
• 49 Open section
• 50 Base material for forming a valved stent (third embodiment)
• 51 Base material cover
• 52 Open section
• 53 Base material body
• 54 Entry groove
• 60 Base material for forming a valved stent (fourth embodiment)
• 61 Base material cover
• 62 Bulge
• 64 Open section
• 65 Base material for forming a valved stent (fifth embodiment)
• 66 Base material body
• 67 Entry groove
• 68 Lateral groove
• 69 Base material cover
• 70 Open section
• 71 Lateral open section

Claims (15)

1. A valved stent indwelled in a blood vessel to provide a valve function to the blood vessel, comprising:

a cylindrical stent body; and

a leaflet composed of connective tissue that protrudes radially inward from the stent body and is capable of opening/closing the blood vessel in a blood flow direction,

wherein an inside and an outside of the stent body radially communicate with each other.

2. The valved stent according toclaim 1, wherein the stent body is a mesh-like metal member.

3. The valved stent according toclaim 1, wherein the stent is capable of being indwelled in an ampulla with a blood vessel wall of the blood vessel expanding radially outward, and the stent body is set to a length such that the stent body is capable of spanning the ampulla in the blood flow direction and being held on opposite sides.

4. The valved stent according toclaim 1, wherein a plurality of the leaflets are arranged in parallel in a circumferential direction of the stent body, and the plurality of leaflets are integrated at a base end.

5. The valved stent according toclaim 1, wherein a contact section that covers the stent body and comes into contact with the blood vessel wall is composed of connective tissue, and a plurality of the contact sections are continuously formed in the blood flow direction at intervals in the circumferential direction of the stent body to expose the stent body between the plurality of contact sections.

6. The valved stent according toclaim 5, wherein the contact section is formed so as to be aligned with a boundary between the plurality of leaflets in the circumferential direction of the stent body.

7. A base material for forming a valved stent that is placed in an environment with a body tissue material to form film-like tissue on a surface of the base material and form a valved stent including a leaflet protruding radially inward from a stent body, comprising:

a columnar base material body;

a plurality of recesses formed in an outer peripheral surface of the base material body;

an inner cover that covers the recesses to form a leaflet forming space for forming the leaflet; and

an outer cover placed on an outer surface side of the inner cover with the stent body interposed therebetween.

8. The base material for forming a valved stent according toclaim 7, wherein the inner cover and the outer cover have open sections that expose a boundary between the plurality of recesses in the outer peripheral surface of the base material body via the stent body.

9. The base material for forming a valved stent according toclaim 7, further comprising a positioning section that circumferentially positions the base material body, the inner cover, and the outer cover.

10. A method for producing a valved stent comprising:

an assembly step of assembling a base material for forming the valved stent according toclaim 7 by incorporating a stent body between an inner cover and an outer cover;

a placement step of placing the base material for forming the valved stent in an environment with a body tissue material;

a formation step of forming film-like tissue around the base material for forming the valved stent;

a taking-out step of taking out the base material for forming the valved stent covered with tissue from the environment; and

a separation step of integrally delaminating and taking out tissue including the leaflet and the stent body from the base material for forming the valved stent as a valved stent,

wherein the separation step is a step of removing tissue on surfaces of opposite ends of the base material for forming the valved stent and the outer cover, detaching the outer cover, and then central-axially disassembling and taking out the base material body and the inner cover from a lumen of the valved stent.

11. A base material for forming a valved stent that is placed in an environment with a body tissue material to form film-like tissue on a surface of the base material and form a reverse valved stent with an inside and an outside being reversed of a valved stent including a leaflet protruding radially inward from a stent body, comprising:

a columnar base material body; and

a base material cover placed on an outer peripheral side of the base material body with the stent body interposed therebetween.

12. The base material for forming a valved stent according toclaim 11, wherein the base material cover has an open section that exposes the outer peripheral surface of the base material body via the stent body.

13. The base material for forming a valved stent according toclaim 12, wherein the outer peripheral surface of the base material body has an entry groove that connective tissue enters, and the base material cover is placed so that the entry groove is aligned with the open section.

14. The base material for forming a valved stent according toclaim 11, wherein the base material cover has a bulge formed by expanding an outer surface side.

15. A method for producing a valved stent comprising:

an assembly step of assembling a base material for forming the valved stent according toclaim 11 by incorporating a stent body between a base material body and a base material cover;

a placement step of placing the base material for forming the valved stent in an environment with a body tissue material;

a formation step of forming film-like tissue around the base material for forming the valved stent;

a taking-out step of taking out the base material for forming the valved stent covered with tissue from the environment; and

a separation step of integrally delaminating and taking out tissue including the leaflet and the stent body from the base material for forming the valved stent as a reverse valved stent,

wherein the separation step is a step of removing tissue on opposite ends of the base material for forming the valved stent, then central-axially disassembling the base material body and the base material cover, taking out the base material cover from between the leaflet and the stent body, and taking out the base material body from a lumen of the reverse valved stent, and

the method further comprises, after the separation step, a reverse step of reversing an inside and an outside of the reverse valved stent to form a valved stent.

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