JP2023135411A - Valved graft forming substrate - Google Patents

Abstract

To provide a valved graft forming substrate by which a vessel can be formed with a desired thickness.SOLUTION: A valve leaflet formation surface 9 on a body side is set on a columnar substrate body 6. A valve leaflet formation surface 10 on an auxiliary side is set on an auxiliary substrate 7. The auxiliary substrate 7 is freely detachably installed on the end of the substrate body 6. A space between the valve leaflet formation surface 9 on the body side and the valve leaflet formation surface 10 on the auxiliary side is defined as a valve leaflet formation space 12. On the outer peripheral side of the substrate body 6 and the auxiliary substrate 7, there is installed a cylindrical cover substrate 8. A space between the outer peripheral surface of the substrate body 6 as well as of the auxiliary substrate 7 and the inner peripheral surface of the cover substrate 8 is defined as a vessel formation space 13. By installing in an environment in which a biological tissue material exists, a connective tissue is formed on the substrate surface, with a valved graft formed.SELECTED DRAWING: Figure 1

Description

The present invention provides a valve for forming a valve graft having a plurality of leaflets bulging radially inward from a conduit by placing it in an environment where biological tissue material is present to form connective tissue on the surface of the base material. The present invention relates to a graft-forming substrate.

Much research is being conducted into regenerative medicine, which uses artificial materials and cells to revive cells, tissues, and organs that have been lost due to disease or accidents.

Normally, the body has a self-defense function, and when a foreign object such as a thorn invades a shallow part of the body, it tries to push it out of the body. In addition, when a foreign object enters a deep position in the body, fibroblasts gradually gather around it and form a capsule of connective tissue mainly composed of fibroblasts and collagen to cover the foreign object. , is known to isolate foreign substances within the body. As a technique for forming biological tissue from living cells by utilizing this latter self-defense reaction, several techniques have been reported in which a connective tissue body is formed by implanting a base material as a foreign substance in a living body (patented). (See References 1 to 3).

Further, Patent Document 4 discloses that a base material is placed in a living body, connective tissue is formed on the surface of the base material, and an artificial valve having a plurality of leaflets that bulges radially inward from an outer tube part is formed. Discloses a prosthetic valvuloplasty base material for.

JP2007-312821A Japanese Patent Application Publication No. 2008-237896 Japanese Patent Application Publication No. 2010-094476 WO2016/098877A1 (Claim 1)

However, although the base material described in Patent Document 4 can form valve leaflets (valve leaflets) of a desired shape and thickness in the leaflet formation space, the base material is The connective tissue is directly used as the outer tube (conduit), and the outer tube (conduit) cannot be formed to a desired thickness.

The present invention seeks to provide a valved grafting substrate in which a conduit can be formed to a desired thickness.

In order to achieve the above object, the valved graft-forming base material according to the present invention is placed in an environment where biological tissue material is present to form connective tissue on the base material surface, and bulges radially inward from the conduit. This is for forming a valved graft having a plurality of valve leaflets, and includes a columnar base material body and an auxiliary base material that is detachably attached to the end of this base material body. Furthermore, a main body side leaflet formation surface and an auxiliary side leaflet formation surface are set on the base material main body and the auxiliary base material, respectively, and are opposed to each other with an interval corresponding to the leaflet thickness, and this main body side leaflet formation surface The space between the base material body and the auxiliary side leaflet formation surface is used as a leaflet formation space in which connective tissue enters from the entry port on the outer edge to form the leaflet of the valved graft, and the outer peripheral side of the base material body and the auxiliary base material A cylindrical cover base material is provided in the base material main body and the auxiliary base material, and the outer peripheral surface of the base material main body and the auxiliary base material and the inner peripheral surface of the cover base material are opposed to each other with an interval corresponding to the conduit thickness. A conduit forming space is formed between the outer circumferential surface of the graft and the inner circumferential surface of the cover base material, into which connective tissue is allowed to enter to form a conduit of the valved graft.

According to the above configuration, the cylindrical cover base material is provided on the outer peripheral side of the base material main body and the auxiliary base material to constitute the conduit formation space, so connective tissue is allowed to enter the conduit formation space to achieve the desired thickness. can form a conduit. Moreover, since a conduit is formed between the base material main body and auxiliary base material and the cover base material, quality such as strength can be improved compared to simply forming a conduit on the outer circumferential side of the base material main body and auxiliary base material. I can do it.

In addition, since the main body side leaflet formation surface and the auxiliary side leaflet formation surface are set on the base material main body and the auxiliary base material, the connective tissue is injected into the leaflet formation space formed between the two surfaces from the entrance at the outer edge. While the valve leaflet is being entered, a connection between the conduit and the end of the leaflet can be formed at the entry port.

This makes it possible to form a valved graft in which the ends of the valve leaflets are supported by conduits of high quality and desired thickness, and the valve leaflets flex radially under the pressure of the fluid. The channel can be opened and closed.

Here, "connective tissue" usually refers to a tissue whose main component is collagen and is formed in a living body, but in the description of this specification and claims, This concept also includes tissues that correspond to connective tissue formed in a living body but are formed in an environment outside the living body.

In addition, "biological tissue materials" refer to substances necessary for forming desired biological tissue, such as fibroblasts, smooth muscle cells, endothelial cells, stem cells, ES cells, iPS cells, etc. Examples include animal cells, various proteins (collagen, elastin), sugars such as hyaluronic acid, and various physiologically active substances existing in living bodies such as cell growth factors and cytokines. This "biological tissue material" includes materials derived from mammals such as humans, dogs, cows, pigs, goats, and sheep, birds, fish, and other animals, or equivalent artificial materials.

In addition, "environment in which biological tissue materials exist" refers to the inside of an animal (human, dog, cow, pig, goat, sheep, and other mammals, birds, fish, and other animals) (e.g., limbs, shoulders, etc.). It refers to an artificial environment containing living tissue materials, either subcutaneously (implanted in the abdomen, back, or abdomen), or in vitro in an animal.

Furthermore, a valve tip hole may be formed in the auxiliary base material, which communicates a portion of the valve leaflet formation space corresponding to the distal end of the valve leaflet with the outside of the base material.

According to this configuration, the valve leaflet formation space and the outside of the base material are communicated through the valve tip hole, so connective tissue can simply enter the leaflet formation space from the outside of the base material through the conduit formation space and the entry port. Instead, the connective tissue can directly enter the valve leaflet formation space from outside the base material through the valve tip hole, and the time required to form the valve leaflets can be shortened accordingly.

In other words, since the cover base material is provided on the outer periphery of the base material body and the auxiliary base material, the connective tissue needs to enter the duct formation space inside the cover base material and then enter the valve leaflet formation space through the entry port. However, the time required to form the valve leaflets tends to be longer. On the other hand, by forming a valve tip hole in the auxiliary base material and communicating the valve leaflet formation space with the outside of the base material, the connective tissue can also enter through the valve tip hole, and the formation of the valve leaflet. can prevent delays.

Furthermore, the valve leaflet formation space may be set in the shape of the valve leaflet in the closed state, and a common valve tip hole may be formed that communicates the portion corresponding to the tips of the plurality of valve leaflets with the outside of the base material. .

According to this configuration, the leaflet formation space is set in the shape of the valve leaflet in the closed state, so the tips of the plurality of leaflet formation spaces can be brought closer to each other, and the valve formed at the tip of each leaflet formation space can be moved closer to each other. The tip holes can be integrated and shared. This makes it possible to enlarge the opening of the valve tip hole to the outside of the base material, making it easier for connective tissue to enter the valve tip hole from the outside of the base material, and forming high-quality valve leaflets more reliably. The time required to form the valve leaflets can be shortened.

Moreover, by setting the valve leaflet formation space to the shape of the valve leaflets in the closed state, the valve leaflets can be formed in the closed state, and compared to the case where the leaflets are formed in the open state, it is possible to form the valve leaflets in the closed state. For valved grafts, the possibility of regurgitation due to delayed closure of the valve leaflets can be reduced.

Furthermore, a promoting hole is formed in the auxiliary base material to communicate the valve leaflet formation space with the conduit forming space and promote the invasion of connective tissue into the valve leaflet forming space, and an area extending from the end surface of the auxiliary base material to the promoting hole. Additionally, a cutting slit for cutting the connective tissue formed inside the promoting hole may be formed.

According to this configuration, since the promoting hole is formed in the auxiliary base material, it is possible to promote the invasion of connective tissue from the conduit formation space on the outside of the auxiliary base material to the valve leaflet formation space on the inside. In this case, the connective tissue formed inside the promoting hole will connect the conduit of the valved graft to the valve leaflet with the auxiliary base material in between, but since a cutting slit is formed in the auxiliary base material, , the connective tissue formed inside the promoting hole can be easily cut. This allows the valved graft to be efficiently formed and removed from the valved graft forming substrate without damaging the valved graft.

As described above, according to the present invention, a cylindrical cover base material is provided on the outer peripheral side of the base material main body and the auxiliary base material to constitute a conduit forming space, and connective tissue is infiltrated into this conduit forming space to form a conduit. Therefore, the conduit of the valved graft can be formed to a desired thickness and its quality such as strength can be improved.

In addition, by invading the connective tissue from the conduit formation space into the leaflet formation space between the main body side leaflet formation surface and the auxiliary side leaflet formation surface through the entry port on the outer edge, the valve leaflet formation space is While forming the leaflet of the valved graft, a connection between the conduit and the end of the leaflet can be formed at the entry port.

A perspective view of a valved graft-forming substrate according to the present invention Perspective view of the base material body and auxiliary base material with the cover base material removed Perspective view of Figure 2 from the opposite side Perspective view of the base material body (a) is a plan view of the base material body, (b) is a sectional view taken along A-A Diagram illustrating the procedure for forming a valved graft using a valved graft formation base material FIG. 2 is a perspective view of a valved graft, (a) showing the closed state and (b) showing the open state.

EMBODIMENT OF THE INVENTION Hereinafter, the form for implementing the valved graft formation base material based on this invention is demonstrated using drawing.

As shown in FIGS. 1 to 5, a valved graft-forming substrate 1 is placed in an environment where biological tissue material is present to form connective tissue 2 on the substrate surface and expand radially inward from a conduit 3. It is for forming a valve graft 5 which is used as a heart valve graft, for example, and has a plurality of valve leaflets 4 that extend out, and is detachably attached to a columnar base material body 6 and an end of the base material body 6. It includes an auxiliary base material 7 and a cylindrical cover base material 8 provided on the outer peripheral side of the base material main body 6 and the auxiliary base material 7.

Furthermore, a main body side leaflet formation surface 9 and an auxiliary side leaflet formation surface 10 are respectively set on the base material main body 6 and the auxiliary base material 7 with an interval corresponding to the leaflet thickness. The space between the formation surfaces 9 and 10 is a leaflet formation space 12 in which the connective tissue 2 enters through the entry port 11 at the outer edge to form the leaflet 4 of the valved graft 5. The outer circumferential surface of the material 7 and the inner circumferential surface of the cover base material 8 face each other with an interval corresponding to the thickness of the conduit, and the connective tissue 2 is allowed to enter between these surfaces to form the conduit 3 of the valved graft 5. A conduit forming space 13 is formed.

The base body 6 has a cylindrical shape made of a polymeric material such as acrylic resin, and has three body-side leaflet formation surfaces 9 partitioned by a central Y-shaped partition wall 14 at its ends. has been done. Each main body-side valve leaflet formation surface 9 is composed of the wall surface of the partition wall 14 and a curved surface that extends radially outward while being inclined from the lower edge in the direction of the center axis of the base material, and is upstream of the valve leaflet 4 in the closed state. The shape is set to correspond to the surface.

The main body side valve leaflet formation surface 9 has five variables, for example, valve diameter (D), valve closure angle (θ), valve center length (L), commissure height (H), and distance between commissures (a). It can be set by using interpolation processing using a so-called non-uniform rational B-spline (NURBS). Here, the valve diameter (D) corresponds to the outer diameter of the base material main body 6, and the valve closing angle (θ) is, for example, 20 deg, which corresponds to the inclination angle with respect to the base material cross section at the outer edge of the main body side valve leaflet formation surface 9. Correspondingly, the valve center length (L) is, for example, 13.5 mm, which corresponds to the length from the lower edge of the partition wall 14 to the outer edge of the main body side valve leaflet formation surface 9, and the commissure height (H) is, for example, 14.2 mm corresponds to the height in the direction of the center axis of the base material from the outer edge of the valve leaflet formation surface 9 on the main body side to the tip of the partition wall 14, and the distance between commissures (a) corresponds to the thickness of the partition wall 14. do.

A notch 15 is formed in the outer edge of the partition wall 14 in the radial direction so that the adjacent leaflet formation spaces 12 are continuous with a space of sufficient thickness, and the valve graft 5 is formed with a sufficient thickness. A commissure portion 16 having a predetermined strength is formed.

The auxiliary base material 7 is made of a polymeric material such as acrylic resin and has a cylindrical shape, and has a Y-shaped slit 18 formed in a range from the end surface on the center side of the base material to the end plate 17 on the outer end side of the base material. The inner surface and the end surface on the center side of the base material divided into three by the slit 18 constitute the auxiliary leaflet formation surface 10. By inserting the partition wall 14 into the slit 18 and fitting the wall tip 19 into the fitting groove 20 formed in the end plate 17, the auxiliary base material 7 is attached to the end of the base material main body 6. The auxiliary side leaflet formation surface 10 faces the main body side leaflet formation surface 9 to form a leaflet formation space 12.

The distance of the auxiliary side leaflet formation surface 10 from the main body side leaflet formation surface 9 is set in a range of, for example, 0.2 mm to 2.0 mm for each position on the surface, and for example, the distance from the main side valve leaflet formation surface 9 is set in the range of 0.2 mm to 2.0 mm, and the distance is set in the range of, for example, 0.2 mm to 2.0 mm. The valve leaflet 4 is formed to have a desired leaflet thickness distribution while taking this into consideration.

The width of the slit 18 is equal to the sum of the thickness of each side end of the two adjacent leaflet formation spaces 12 and the thickness of the partition wall 14, and the width of the slit 18 is equal to the sum of the thickness of the partition wall 14 and the commissure of the valve graft 5. The width of the portion 16 is set to a sufficient size, and the commissure portion 16 having a predetermined strength is formed.

A Y-shaped valve tip hole 21 is formed in the end plate 17 of the auxiliary base material 7 to expose the center portion of the wall tip 19 of the partition wall 14, and the valve tip hole 21 is made to have a width of, for example, 0.5 mm or more. The common valve tip hole 21 communicates between a portion of the valve leaflet formation space 12 corresponding to the tips of the plurality of valve leaflets 4 and the outside of the base material.

A promoting hole 22 is formed on the circumferential surface of the auxiliary base material 7 to communicate the valve leaflet formation space 12 and the duct formation space 13, and promotes the intrusion of the connective tissue 2 from the duct formation space 13 into the valve leaflet formation space 12. It is supposed to be done. Furthermore, a cutting slit 23 is formed in the range that opens in the end plate 17 and reaches the promoting hole 22. When removing the valved graft 5, a scalpel or the like is inserted into the cutting slit 23, and the inside of the promoting hole 22 is inserted. The connective tissue 2 that has been formed and connects the inside and outside of the auxiliary base material 7 is cut.

The cover base material 8 has a cylindrical shape made of a polymeric material such as acrylic resin, and has a projection 25 projecting radially outward from the end plate 17 of the auxiliary base material 7 in a recess 24 formed at its end. By fitting them together, it is attached to the outer peripheral sides of the base material main body 6 and the auxiliary base material 7 with a constant interval of about 2 mm, for example, and a conduit is formed between the outer peripheral surfaces of the base material main body 6 and the auxiliary base material 7. A forming space 13 is configured. An entry hole 26 is formed in the cover base material 8 so as to extend over almost the entire surface, so that the connective tissue 2 can easily enter the conduit forming space 13 from the outside of the base material.

Here, the material of the valved graft formation base material 1 has a strength (hardness) that will not be significantly deformed when implanted in a living body, is chemically stable, and can withstand loads such as sterilization. Resins that are resistant and have no or little eluate that irritates living bodies are preferred, and examples include, but are not limited to, acrylic resins as described above.

Next, a method for producing the valved graft 5 using the valved graft forming base material 1 as described above will be described.

As shown in FIG. 6, this production method includes an "installation step" in which the valved graft-forming base material 1 is installed in an environment where biological tissue material exists, and connective tissue 2 is placed around the valved graft-forming base material 1. a "formation step" in which the connective tissue 2 is formed and infiltrated into the valve leaflet formation space 12 and a conduit formation space 13; and a "removal step" in which the valved graft formation base material 1 covered with the connective tissue 2 is taken out from the environment. ” and a “separation step” of separating the connective tissue 2 from the valved graft forming substrate as a valved graft 5 including a conduit 3 and a valve leaflet 4 .

<Installation process>
After attaching the auxiliary base material 7 to the end of the base material body 6, the cover base material 8 is attached to the outer periphery of the base material body 6 and the auxiliary base material 7 so as to fit into the protrusion 25, and the valved graft forming base material is formed. Assemble 1. Furthermore, the assembled graft-forming base material 1 with valves is placed in an environment where biological tissue material exists, such as under the skin of a goat (FIG. 6(a)).

The environment in which the living tissue material exists includes the inside of an animal's living body (for example, implanted subcutaneously or intraperitoneally), or the artificial environment such as a solution in which the living tissue material is suspended outside the animal's living body. When the valved graft-forming substrate 1 is placed in an artificial environment, various culture conditions may be set and cell culture may be performed in a clean environment according to known methods. As biological tissue materials, those derived from mammals such as goats, dogs, cows, pigs, rabbits, sheep, and humans, those derived from birds, fish, and other animals, or artificial materials can also be used.

<Formation process>
After the installation process, after a predetermined period of time, for example, about three months, connective tissue 2 is formed around the valved graft formation base material 1, and the connective tissue 2 is formed at the end opening of the conduit formation space 13. and enters the conduit forming space 13 through the entry hole 26 of the cover base material 8. Furthermore, the connective tissue 2 that has entered the conduit formation space 13 enters the valve leaflet formation space 12 through the entry port 11, the slit 18, and the promotion hole 22, and the connective tissue 2 outside the base material directly passes through the valve tip hole 21. It invades the valve leaflet formation space 12 (FIG. 6(b)).

In this forming process, by providing the valve tip holes 21, in addition to entering through the conduit forming space 13, the connective tissue 2 outside the base material can directly enter the valve leaflet forming space in a relatively short time. Connective tissue 2 is formed in 12. In particular, since the plurality of valve leaflet formation spaces 12 are communicated with the outside of the base material through a common valve tip hole 21 and the valve leaflet hole 21 is enlarged, the connective tissue 2 can more easily enter into the valve leaflet formation space 12. promoted. Connective tissue 2 is composed of fibroblasts and extracellular matrix such as collagen.

<Removal process>
After the connective tissue 2 is sufficiently formed in the valve leaflet formation space 12 and the conduit formation space 13 through the formation process for a predetermined time, the valved graft formation base material 1 covered with the connective tissue 2 is placed in the presence of biological tissue material. Perform the extraction process to remove the material from the environment.

<Separation process>
The connective tissue 2 covering the outer peripheral surface of the cover base material 8 is removed while cutting with a scalpel or the like between the connective tissue 2 formed inside the penetration hole 26 of the cover base material 8, and a graft with a valve is formed. The connective tissue 2 at both ends of the base material 1 is removed. Furthermore, the cover base material 8 is removed after deforming and peeling the connective tissue 2 in the conduit forming space 13 with tweezers or the like so as to leave it on the base material main body 6 and the auxiliary base material 7 (FIG. 6(c)).

By removing the cover base material 8, the connective tissue 2 forming the conduit 3 is exposed, and the connective tissue 2 formed inside the penetration hole 26 of the cover base material 8 remains in a protruding shape on the surface thereof. However, even if there is a protrusion on the outer circumferential surface of the conduit 3, it is not necessary to remove it because it does not affect the blood flow or the like.

A scalpel or the like is inserted into the cutting slit 23 covered with the connective tissue 2 to cut the connective tissue 2 formed inside the promoting hole 22 of the auxiliary base material 7 to form the duct 3 and the valve leaflets 4. The connective tissue 2 inside and outside the base material 7 is separated. Furthermore, after removing the auxiliary base material 7 while peeling the connective tissue 2 from the outer peripheral surface and the auxiliary leaflet formation surface 10, the connective tissue 2 covering the wall tip 19 of the partition wall 14 of the base material body 6 is removed. At the same time, the connective tissue 2 inside the promoting hole 22 remaining as a protrusion on the conduit 3 and the valve leaflet 4 is excised (FIG. 6(d)).

The valved graft 5 is obtained by separating the connective tissue 2 from the base material body 6 so as to be peeled off from the outer peripheral surface of the base material body 6 and the valve leaflet formation surface 9 on the body side (FIG. 6(e)).

As shown in FIG. 7, the valved graft 5 produced using the valved graft formation base material 1 is, for example, a heart valve graft that is implanted into a blood vessel such as the aorta that exits the heart to impart a valve function. A plurality of valve leaflets 4 bulging radially inward from the conduit 3 are displaced inwardly and outwardly by the pressure of the fluid flowing inside the conduit 3, thereby opening and closing the flow path inside the conduit 3.

In the valve leaflet 4, the commissure part 16 formed in the slit 18 and the entry port 11 of the valved graft formation base material 1 and the valve base are connected to the conduit 3, and the flow direction of the flow path is from the distal side to the proximal side. At this time, the pressure of the fluid that attempts to enter between the valve leaflet 4 and the conduit 3 causes the valve leaflet 4 to bend radially inward and close the flow path (FIG. 7(a)). On the other hand, when the flow direction of the flow path is from the proximal end to the distal end, the valve leaflets 4 are bent radially outward by the flow to open the flow path (FIG. 7(b)).

Since the valved graft 5 produced using the valved graft formation base material 1 is formed with its valve leaflets 4 in a closed state, the free state is in the closed state, and regurgitation occurs due to the delay in closure. It is possible to suppress the fear.

Note that the present invention is not limited to the above-described embodiments, and changes can be made as appropriate within the scope of the present invention. For example, in the above embodiment, the tricuspid valve was specifically explained as an example, but the valve may have any number of cusps, such as a bicuspid valve or a four-cuspid valve. Moreover, the penetration hole 26 of the cover base material 8, the promotion hole 22 of the auxiliary base material 7, and the cutting slit 23 can be omitted as appropriate. Further, the leaflet hole is not limited to a common hole, and may be one leaflet hole for each leaflet formation space. Furthermore, the leaflet hole may be omitted.

1 Valved graft formation base material 2 Connective tissue 3 Conduit 4 Valve leaflet 5 Valved graft 6 Base material body 7 Auxiliary base material 8 Cover base material 9 Main body side leaflet formation surface 10 Auxiliary side leaflet formation surface 11 Entry port 12 Valve Leaflet formation space 13 Conduit formation space 14 Partition wall 15 Notch 16 Commissure 17 End plate 18 Slit 19 Wall tip 20 Fitting groove 21 Leaflet hole 22 Promotion hole 23 Cutting slit 24 Recess 25 Projection 26 Penetration hole D Valve diameter θ Valve closing angle L Valve center length H Commissure height a Distance between commissures

Claims (4)

A valved graft-forming group for placing in an environment where biological tissue material is present to form connective tissue on the surface of the substrate to form a valved graft having a plurality of leaflets bulging radially inward from a conduit. It is a material,
comprising a columnar base material body and an auxiliary base material detachably attached to the end of the base material body,
A main body side leaflet formation surface and an auxiliary side leaflet formation surface are respectively set on the base material main body and the auxiliary base material, and are opposed to each other with an interval corresponding to the leaflet thickness, and the main body side leaflet formation surface and The space between the auxiliary leaflet formation surface and the leaflet formation surface is defined as a leaflet formation space in which connective tissue is infiltrated from the entry port on the outer edge to form the leaflet of the valved graft;
A cylindrical cover base material is provided on the outer peripheral side of the base material main body and the auxiliary base material, and the outer peripheral surface of the base material main body and the auxiliary base material and the inner peripheral surface of the cover base material are spaced apart from each other corresponding to the thickness of the conduit. The space between the outer circumferential surfaces of the base material main body and auxiliary base material and the inner circumferential surface of the cover base material, which face each other with an open space, is used as a conduit forming space in which connective tissue is infiltrated to form a conduit of the valved graft. Features a valved graft-forming substrate. The valve-equipped valve according to claim 1, characterized in that the auxiliary base material is formed with a valve tip hole that communicates a portion corresponding to the tip of the valve leaflet in the valve leaflet formation space with the outside of the base material. Grafting substrate. The valve leaflet formation space is set in the shape of the valve leaflet in a closed state, and a common valve tip hole is formed that communicates a portion corresponding to the tip portions of the plurality of valve leaflets with the outside of the base material. The valved grafting substrate of claim 2. A promotion hole is formed in the auxiliary base material to communicate the valve leaflet formation space with the conduit formation space to promote the invasion of connective tissue into the valve leaflet formation space, and the promotion hole extends from the end surface of the auxiliary base material. 4. The valved graft-forming base material according to claim 1, wherein a cutting slit for cutting the connective tissue formed inside the promoting hole is formed in the region.

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