JP7698827B2 - Structural assembly for forming connective tissue body and method for forming connective tissue body - Google Patents

Description

This disclosure relates to a structural assembly for forming connective tissue bodies and a method for forming connective tissue bodies.

In recent years, there has been active research into regenerative medicine, which uses artificial materials and cells to restore the functions of cells, tissues, organs, etc. lost due to illness or accidents.

For example, if a foreign body penetrates deep inside the body, fibroblasts gradually gather around the foreign body, forming connective tissue mainly composed of fibroblasts and collagen. Research is being conducted into a technology that utilizes this reaction to form connective tissue by implanting a foreign body inside the body.

For example, Patent Document 1 describes a connective tissue body-forming substrate that is capable of forming a membrane-like connective tissue body on the substrate surface by placing it in an environment where a biological tissue material is present, and that is characterized in that two tissue-forming surfaces that form connective tissue are provided facing each other across a tissue-forming space so that both sides of the membrane-like connective tissue body are formed to match the substrate surface, and at least one of the tissue-forming surfaces has a slit that connects the tissue-forming space with the outside of the substrate. Also described is a connective tissue body-forming substrate that is provided with a number of central substrates with the tissue-forming surface set on the outer circumferential surface, and a storage substrate that contains the central substrates and has a number of storage sections with the tissue-forming surface set on the inner circumferential surface, and in which the slits are formed in the storage substrate.

Patent Document 1 describes how a connective tissue formation substrate is implanted as a foreign body in a living body such as a human or placed in a culture device, and a connective tissue is formed inside the connective tissue formation substrate. The connective tissue is then obtained by removing the connective tissue formation substrate from the living body or culture device.

When so-called autotransplants or allotransplants are performed to form connective tissue bodies inside the human body, it is necessary to make an incision and insert the connective tissue body formation substrate into the human body, suture the incision after insertion, make another incision to remove the connective tissue body formation substrate from the body, and suture the incision again, which places a heavy burden on the human body due to the multiple procedures. In addition, since the connective tissue body formation substrate is implanted into the human body, it is difficult to increase the size or amount of the connective tissue body formation substrate, and it is difficult to mass-produce connective tissue bodies by a single implantation of the connective tissue body formation substrate.

As a powerful means of mass-producing connective tissue bodies, it has been considered to implant a large connective tissue body formation substrate into an animal that can have a larger implantation area than humans, and produce a sheet-like connective tissue body with a large area. However, unlike humans, it is difficult to control the movements and movements of animals other than humans. Therefore, the force generated when walking is very large, and part of the connective tissue body formation substrate during implantation may break through the skin of the large animal and come out. If the part of the connective tissue body formation substrate that has come out gets caught on a fence in a ranch and the animal walks while walking, the skin may tear, or the connective tissue body formed in the substrate or the animal may become infected with bacteria through the torn wound. Therefore, when a connective tissue body formation substrate having multiple connected containers as in Patent Document 1 is used, the connective tissue body formation substrate during implantation may break through the skin or be damaged in the living body, causing problems such as the skin tear described above, making it difficult to grow the connective tissue body or maintain the quality of the connective tissue body.

In addition, when forming connective tissue bodies using a culture device, extremely expensive equipment is required compared to the method of implanting a substrate for forming connective tissue bodies in a living body.

International Publication No. 2016/076416

The object of the present disclosure is to provide a structural assembly for forming a connective tissue body and a method for forming a connective tissue body that can be implanted in a living body other than a human, and that is excellent in at least one of the following: ease of insertion into the living body, ease of removal from the living body, stability after implantation in the living body, and productivity of the connective tissue body.

[1] A structure assembly for connective tissue formation comprising a plurality of connective tissue body formation structures each having a tubular support member and a container member for accommodating the support member, the plurality of connective tissue body formation structures being arranged in parallel, at least one of the plurality of connective tissue body formation structures being detachably coupled to an adjacent connective tissue body formation structure, a connective tissue body formation space in which connective tissue can be formed is provided between the support member and the inner surface of the container member, and a communication portion is provided in the container member for communicating the connective tissue body formation space with the outside of the connective tissue body formation structure.
[2] The structure assembly for forming a connective tissue body described in [1] above, wherein the multiple structures for forming a connective tissue body are arranged two-dimensionally.
[3] A structure assembly for forming a connective tissue body described in [1] or [2] above, wherein at least one of the plurality of structures for forming a connective tissue body is detachably bonded to an adjacent structure for forming a connective tissue body via a weak adhesive portion.
[4] A structure assembly for forming a connective tissue body described in [1] or [2] above, wherein at least one of the plurality of structures for forming a connective tissue body is detachably connected to an adjacent structure for forming a connective tissue body via a connecting portion.
[5] The structure assembly for forming a connective tissue body described in [4] above, wherein the density of the connecting portion is lower than the density of the containing member.
[6] A structure assembly for forming a connective tissue body according to any one of [1] to [5] above, wherein a groove portion extending along the longitudinal direction of the support member is provided between at least one of the plurality of connective tissue body forming structures.
[7] A structure assembly for forming a connective tissue body according to any one of [1] to [6] above, wherein all of the structures for forming a connective tissue body are detachably connected to adjacent structures for forming a connective tissue body.
[8] A structure assembly for forming a connective tissue body described in any one of [1] to [7] above, wherein at least one of the plurality of structures for forming a connective tissue body is movably connected to an adjacent structure for forming a connective tissue body.
[9] A structure assembly for forming a connective tissue body according to any one of [1] to [8] above, wherein all of the structures for forming a connective tissue body are movably connected to adjacent structures for forming a connective tissue body.
[10] A structure assembly for forming a connective tissue body according to any one of [1] to [9] above, wherein at least one terminal corner of the container member constituting the structure for forming a connective tissue body arranged at the end among the plurality of structures for forming a connective tissue body arranged in parallel is provided with a corner inclined surface connecting the adjacent terminal side surface and end face between the adjacent terminal side surface and end face.
[11] The connective tissue formation structure assembly described in [10] above, wherein a covering portion made of a material softer than the container member is provided on at least the inclined corner surface of the container member.
[12] A method for forming a connective tissue body, comprising the steps of: (S-1) inserting and embedding the connective tissue body formation structure assembly described in any one of the above [1] to [11] into a living organism other than a human; (S-2) forming a connective tissue body in the connective tissue body formation space of the connective tissue body formation structure assembly embedded in the living organism; and (S-3) removing from the living organism the connective tissue body formation structure assembly containing the connective tissue body formed in the connective tissue body formation space.
[13] The method for forming a connective tissue body according to the above [12], wherein in the step (S-3), each of the structures for connective tissue body formation constituting the connective tissue body formation structure assembly is taken out from one removal section.

According to the present disclosure, it is possible to provide a structural assembly for forming a connective tissue body and a method for forming a connective tissue body that can be implanted in a living body other than a human and that is excellent in at least one of the following: ease of insertion into the living body, ease of removal from the living body, stability after implantation in the living body, and productivity of the connective tissue body.

FIG. 1 is a perspective view showing an example of a connective tissue formation structure assembly according to an embodiment. FIG. 2 is a perspective view showing an example of the arrangement of structures for forming connective tissue that constitute the connective tissue formation structure assembly of the embodiment. FIG. 3 is a perspective view showing an example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 4 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 5 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 6 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 7 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 8 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 9 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 10 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 11 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 12 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 13 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 14 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 15 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 16 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 17 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 18 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment. FIG. 19 is a perspective view showing another example of a structure for forming a connective tissue structure constituting the connective tissue structure assembly of the embodiment.

The following provides a detailed explanation based on the embodiment.

As a result of extensive research, the present researchers have discovered that by optimizing the configuration of the multiple connective tissue formation structures that make up the connective tissue formation structure assembly, the connective tissue formation structure assembly can be used in living organisms other than humans, and further, is excellent in at least one of the following: ease of insertion into the living organism, ease of removal from the living organism, stability after implantation in the living organism, and productivity of connective tissue bodies; and have completed the present disclosure based on this finding.

The connective tissue formation structure assembly of the embodiment has a plurality of connective tissue formation structures each having a cylindrical support member and a container member that contains the support member, the plurality of connective tissue formation structures are arranged in parallel, at least one of the plurality of connective tissue formation structures is detachably connected to an adjacent connective tissue formation structure, a connective tissue formation space in which connective tissue can be formed is provided between the support member and the inner surface of the container member, and the container member is provided with a communication portion that connects the connective tissue formation space with the outside of the connective tissue formation structure.

Figure 1 is a perspective view showing an example of a structure assembly for forming a connective tissue body according to an embodiment.

As shown in FIG. 1, the connective tissue formation structure assembly 1 has a plurality of connective tissue formation structures 10. The plurality of connective tissue formation structures 10 have a support member 20 and a housing member 30, and are arranged in parallel. In the connective tissue formation structure assembly 1, at least two or more connective tissue formation structures 10 are arranged in parallel in succession.

The support member 20 constituting each connective tissue body formation structure 10 is cylindrical and supports the connective tissue body formed in the connective tissue body formation space 32 from the inside as described below. In order to uniformize the shape of the connective tissue body of the hollow cylindrical body formed in the connective tissue body formation space 32, it is preferable that the external dimensions in the short side direction of the cylindrical support member 20 are constant over the longitudinal direction L perpendicular to the short side direction of the support member 20. In addition, in order to reduce the area difference between the inner surface and the outer surface of the connective tissue body of the hollow cylindrical body formed, it is preferable that the support member 20 is cylindrical. If the support member 20 is a solid body, it is easy to wash the support member 20. If the support member 20 is a hollow body, the weight of the connective tissue body formation structure assembly 1 and the connective tissue body formation structure 10 can be reduced and material costs can be reduced. When the connective tissue formation structure assembly 1 or the connective tissue formation structure 10 becomes lighter, the burden on the non-human living body (hereinafter also simply referred to as the living body) is reduced, and the position of the connective tissue formation structure assembly 1 embedded in the living body can be prevented from dropping due to gravity.

The housing member 30 constituting each connective tissue formation structure 10 houses the support member 20 along the longitudinal direction L of the support member 20. The housing member 30 housing the support member 20 therein is a hollow tubular body extending along the longitudinal direction L of the support member 20, for example, a hollow rectangular tubular body as shown in FIG. 1. The housing member 30 houses the entire support member 20, but one end of the support member 20 may protrude from an opening 31 provided in one end wall of the housing member 30.

The other end of the support member 20 is connected to the inside of the other end wall that faces the end wall in which the opening 31 of the storage member 30 is provided. For example, the other end of the support member 20 may be integrally connected to the storage member 30, may be connected to the storage member 30 via a connecting member (not shown), or may be screwed to the storage member 30.

In the multiple connective tissue formation structures 10, a connective tissue formation space 32 is provided between the side surface 21 of the support member 20 and the inner surface 41 of the storage member 30. The side surface 21 of the support member 20 extends along the longitudinal direction L between both ends of the support member 20. The inner surface 41 of the storage member 30 extends along the longitudinal direction L inside the storage member 30 and faces the side surface 21 of the support member 20. The inner surface 41 of the storage member 30 covers the side surface 21 of the support member 20 from the outside with a distance d between the side surface 21 of the support member 20 and the inner surface 41 of the storage member 30. The connective tissue formation space 32 extends in an annular shape along the longitudinal direction L of the support member 20 inside the storage member 30 between the side surface 21 of the support member 20 and the inner surface 41 of the storage member 30. The connective tissue formation space 32 is a space in which a connective tissue can be formed.

The shape of the inner surface 41 of the storage member 30 may be changed as appropriate depending on the outer shape of the support member 20. It is preferable that the distance d between the side surface 21 of the support member 20 and the inner surface 41 of the storage member 30 is constant so that the thickness of the connective tissue of the hollow cylindrical body formed in the connective tissue formation space 32 is uniform. Here, since the support member 20 is cylindrical, it is preferable that the inner surface 41 of the storage member 30 is cylindrical, and in that case the connective tissue formation space 32 extends in an annular shape along the longitudinal direction L of the support member 20.

In multiple connective tissue body formation structures 10, at least one communication portion 33 is provided on the side wall 42 of the storage member 30. The side wall 42 of the storage member 30 extends along the longitudinal direction L of the support member 20. The communication portion 33 provided on the storage member 30 penetrates the side wall 42 of the storage member 30 and communicates the connective tissue body formation space 32 with the outside of the connective tissue body formation structure 10. The communication portion 33 penetrating the side wall 42 extends along the longitudinal direction L, for example, and is provided on one side wall 42.

The configuration of the communication part 33 is not particularly limited, and for example, multiple communication parts 33 may be provided discontinuously. When multiple communication parts 33 are provided discontinuously, the multiple communication parts 33 may extend along the same direction or along different directions. From the viewpoint of forming a high-quality connective tissue, it is preferable that the communication part 33 extends over the entire surface in the longitudinal direction L with respect to the side surface 21 of the support member 20 as shown in FIG. 1. The communication part 33 is connected to, for example, an opening 31 provided in one end wall of the storage member 30.

When the connective tissue formation structure assembly 1 is implanted in a living body other than a human, the connective tissue enters the connective tissue formation space 32 from the outside of the connective tissue formation structure 10 through the communication part 33, and a connective tissue extending in a cylindrical shape along the longitudinal direction L of the support member 20 is formed in the connective tissue formation space 32. The connective tissue is composed of an extracellular matrix such as fibroblasts and collagen. The connective tissue is used in a cylindrical or sheet-like shape and is used for transplantation of the pericardium, dura mater, skin, valves, cornea, blood vessels, digestive tract, trachea, etc. into humans, companion animals, livestock animals, rare animals for exhibition, etc.

The material constituting the support member 20 and the housing member 30 is not particularly limited, but it is preferable that the material has a strength (hardness) sufficient to suppress large deformation when implanted in a living body, chemical stability, and resistance to sterilization treatment by autoclave or the like, and does not release substances that have adverse effects on the connective tissue to be formed or the living body, or does not release such substances in large amounts. From this perspective, the material constituting the support member 20 and the housing member 30 is preferably a resin material such as an acrylic resin or a silicone resin, or a metal material with high rust resistance such as stainless steel, titanium, cobalt, chromium, or a nickel-titanium alloy. The surface of the support member 20 and the housing member 30 may also be covered with the above-mentioned resin material or metal material. The above-mentioned resin material forms the connective tissue in the living body faster than the above-mentioned metal material.

In the connective tissue body forming structure assembly 1, it is preferable that the side surface 21 of the support member 20 is formed from a resin material that easily forms connective tissue, and the outer surface of the container member 30 is formed from a metal material that does not easily form connective tissue. In the connective tissue body forming structure assembly 1 configured in this way, the rate at which connective tissue is formed in the connective tissue body forming space 32 is faster than the rate at which connective tissue is formed on the outer surface of the container member 30. The metal material that constitutes the outer surface of the container member 30 slows down the blocking of the communication part 33 by the connective tissue formed on the outer surface of the container member 30. Before the communication part 33 is blocked by connective tissue, the connective tissue is formed in the connective tissue body forming space 32. Therefore, a connective tissue body having a desired shape according to the shape of the connective tissue body forming space 32 can be easily formed.

As shown in FIG. 1, the connective tissue formation structure assembly 1 has a plurality of connective tissue formation structures 10 that are smaller than the connective tissue formation structure assembly 1. At least one of the plurality of connective tissue formation structures 10 is detachably connected to an adjacent connective tissue formation structure 10. As shown in FIG. 1, in the connective tissue formation structure assembly 1, two adjacent side walls 42a that do not have a communication portion 33 of the storage member 30 are detachably connected to each other.

The bonding strength at which adjacent connective tissue formation structures 10 are detachably bonded is a strength at which adjacent connective tissue formation structures 10 are easily separated from the two side walls 42a without using a cutting machine or shearing machine, and without applying strong force, for example, by a force greater than that during normal activity caused by abnormal movement of the organism or a collision between the organism and an obstacle such as a ranch fence during implantation of the connective tissue formation structure assembly 1 in the organism, or by normal intentional force applied by a human hand. When such a force is applied to the connective tissue formation structures 10 that are detachably bonded to each other, the connective tissue formation structures 10 may completely separate individually, but it is preferable that the connective tissue formation structures 10 maintain partial bonding. In such a case, the adjacent connective tissue formation structures 10 are not completely separated and are partially bonded. Therefore, all of the connective tissue formation structures 10 that make up the connective tissue formation structure assembly 1 can be removed with a single incision procedure, and the connective tissue formation structure assembly 1 can be easily removed from within the living body.

The connective tissue formation structure assembly 1 is used by being implanted in a living body other than a human. Examples of living bodies other than a human include mammals such as dogs, cows, pigs, horses, goats, sheep, and rabbits, as well as birds, fish, and other animals. Among these, preferred are cows, horses, pigs, and goats, which have a larger implantation area than humans, can produce a large amount of connective tissue with a single implantation, and are widely kept as livestock.

The connective tissue body formation structural assembly 1 is embedded in the subcutaneous tissue of the limbs, shoulders, back, abdomen, etc. After a portion of the epidermis and dermis (hereinafter also referred to as skin) on the outside of the subcutaneous tissue is peeled off from the living body, the connective tissue body formation structural assembly 1 is inserted into the subcutaneous tissue, and then the partially peeled skin is sutured to the living body, thereby embedding the connective tissue body formation structural assembly 1 in the subcutaneous tissue.

A removable lid 34 may be provided on the end surface 43 of the storage member 30 having the openings 31. The lid 34 covers the end surface 43 of the storage member 30 from the outside and closes the multiple openings 31. For example, the inner surface 34b of the lid 34 covering the end surface 43 is provided with multiple recesses (not shown) at positions facing each opening 31. Each recess of the lid 34 closes each opening 31. The bottom surface of each recess abuts against one end surface 22 of the support member 20. The material constituting the lid 34 is the same as that of the storage member 30. When the multiple connective tissue body formation structures 10 are separated from each other from the side wall 42a, the lid 34 separates along the surface 34a that allows easy separation.

As described above, the connective tissue body formation structure assembly 1 comprises multiple connective tissue body formation structures 10. When inserting the connective tissue body formation structure assembly 1 comprising multiple connective tissue body formation structures 10 into a living body, the connective tissue body formation structure assembly 1 comprising multiple connective tissue body formation structures 10 can be embedded at one location in the subcutaneous tissue by performing a single incision procedure and inserting the connective tissue body formation structure assembly 1 from a single incision. In this way, the connective tissue body formation structure assembly 1 can be easily inserted into a living body through a short and simple operation, and the productivity of the connective tissue body can be improved.

During the implantation of the connective tissue body formation structure assembly 1, a force larger than that during normal activity may be applied to the connective tissue body formation structure assembly 1 due to the abnormal behavior of the living body or a collision between the living body and an obstacle. When such a force is applied, if the force is small, the connective tissue body formation structures 10 constituting the connective tissue body formation structure assembly 1 during implantation are not completely separated but are partially bonded, and the bonded state is maintained. Therefore, the connective tissue body formation structure assembly 1 can be easily removed with a single incision procedure. Furthermore, because the force applied to the connective tissue body formation structure assembly 1 is small, damage caused by the connective tissue body formation structure assembly 1 during implantation to subcutaneous tissue, skin, etc. is suppressed.

In addition, when the force is large, the connective tissue body formation structure 10 constituting the connective tissue body formation structure assembly 1 is easily separated from the side wall 42a by this force. In this way, the force applied to the connective tissue body formation structure assembly 1 and the connective tissue body formation structure 10 is reduced by the separation of the connective tissue body formation structure 10. Furthermore, damage to the connective tissue body formation structure assembly 1 during implantation is suppressed. The separation of the connective tissue body formation structure 10 has a cushioning effect that reduces the force applied to the connective tissue body formation structure assembly 1. Therefore, the connective tissue body formation structure 10, which is smaller than the connective tissue body formation structure assembly 1, can be suppressed from breaking through the skin and coming out of the living body, and can suppress damage to the subcutaneous tissue, skin, etc. In this way, the connective tissue body formation structure assembly 1 has excellent stability after implantation. In addition, even if the connective tissue body formation structure 10 is separated, the state in which multiple connective tissue body formation structures 10 are embedded in one place in the subcutaneous tissue is maintained. Therefore, all of the connective tissue formation structures 10 constituting the connective tissue formation structure assembly 1 can be easily removed with a single incision procedure. In this way, the connective tissue formation structure assembly 1 can be easily removed from within the living body.

On the other hand, the conventional substrate for forming a connective tissue body is used for humans and is also embedded in the abdominal cavity. Furthermore, the multiple storage parts constituting the conventional substrate for forming a connective tissue body are not separably connected, but are integrally constructed. Therefore, when the conventional substrate for forming a connective tissue body is embedded in subcutaneous tissue, even if the substrate for forming a connective tissue body is subjected to a force larger than normal, the multiple storage parts are not separated, and in some cases, the substrate for forming a connective tissue body may be damaged. The substrate for forming a connective tissue body subjected to such a large force is likely to damage the subcutaneous tissue or skin, and in some cases, at least a part of the substrate for forming a connective tissue body may break through the skin and be exposed to the outside of the body. If the substrate for forming a connective tissue body breaks through the skin and is exposed to the outside of the body, the growth of the connective tissue body becomes insufficient, making it difficult to form a connective tissue body of good quality. Thus, the conventional substrate for forming a connective tissue body does not have good stability after being embedded in the body.

Furthermore, when multiple connective tissue bodies are formed using a conventional connective tissue body formation substrate that does not have multiple storage sections, one connective tissue body is formed from one connective tissue body formation substrate, so multiple connective tissue body formation substrates must be implanted by multiple insertion procedures. In some cases, multiple incision procedures are performed to implant multiple connective tissue body formation substrates at multiple locations in the body. For this reason, conventional connective tissue body formation substrates impose a large burden on the animal, the procedures are complicated, and mass production of connective tissue bodies is not easy.

Thus, unlike conventional connective tissue body formation substrates, the connective tissue body formation structure assembly 1 of the embodiment focuses on the configuration of multiple connective tissue body formation structures that constitute the connective tissue body formation structure assembly. The connective tissue body formation structure assembly 1 can be separated into multiple connective tissue body formation structures 10 to reduce its size. From the viewpoint of improving the productivity of connective tissue bodies, the connective tissue body formation structure assembly 1 is used in living organisms other than humans and is embedded in subcutaneous tissue. Multiple connective tissue bodies can be formed by one incision procedure and one insertion of the connective tissue body formation structure assembly 1, i.e., one embedding operation of the connective tissue body formation structure assembly 1. Therefore, the connective tissue body formation structure assembly 1 including multiple connective tissue body formation structures 10 can be easily inserted into a living organism and can improve the productivity of connective tissue bodies. In addition, depending on the magnitude of the force received, the connective tissue body formation structure 1 in the living body can maintain partial connection of the connective tissue body formation structure 10 or separate into connective tissue body formation structures 10 smaller than the connective tissue body formation structure 1, thereby reducing the force applied to the subcutaneous tissue, skin, etc. Damage to the connective tissue body formation structure assembly 1 in the living body is suppressed. In this way, the connective tissue body formation structure assembly 1 has excellent stability after implantation, so that a connective tissue body can be stably formed in the living body. In addition, even if the connective tissue body formation structure 1 separates, the multiple connective tissue body formation structures 10 continue to be embedded in one part of the living body. Therefore, the connective tissue body formation structure 1 can be easily removed from the living body by a single incision procedure.

As shown in FIG. 1, in the connective tissue body formation structure assembly 1, it is preferable that the multiple connective tissue body formation structures 10 are arranged two-dimensionally. In a configuration in which multiple connective tissue body formation structures 10 are arranged two-dimensionally, the multiple connective tissue body formation structures 10 are arranged continuously in parallel. When multiple connective tissue body formation structures 10 are arranged two-dimensionally, the connective tissue body formation structure assembly 1 becomes sheet-like. The sheet-like connective tissue body formation structure assembly 1 can be inserted so as to be easily inserted into subcutaneous tissue. For example, the connective tissue body formation structure assembly 1 is inserted into the living body from an insertion portion formed by incising the living body. The sheet-like connective tissue body formation structure assembly 1 can be inserted while cutting open the subcutaneous tissue when inserting. In addition, since the insertion portion into which the sheet-like connective tissue body formation structure assembly 1 is inserted is linear, the insertion portion can be formed by a simple incision procedure. This makes it even easier to insert the connective tissue body formation structure assembly 1 into the living body. Furthermore, since the sheet-like connective tissue formation structure assembly 1 easily adheres to the living body when implanted, the stability of the connective tissue formation structure assembly 1 after implantation is improved, and a connective tissue with excellent quality can be formed. From the viewpoints of improving the productivity of the connective tissue body, ease of insertion of the connective tissue formation structure 1, and stability after implantation, it is preferable that 2 to 10 connective tissue formation structures 10 are arranged continuously in parallel.

In addition, in a configuration in which multiple connective tissue body formation structures 10 are arranged two-dimensionally, as long as the ease of insertion of the connective tissue body formation structure assembly 1 and the stability after implantation are not reduced, one or more separate connective tissue body formation structures 10 may be attached or detachably attached to a side wall different from the adjacent side walls 42a of the connective tissue body formation structures arranged continuously in parallel, in addition to the multiple connective tissue body formation structures arranged continuously in parallel, as shown in FIG. 2 for example. In this case, the shape of the lid portion 34 is appropriately set according to the arrangement of the connective tissue body formation structures 10 so as to cover all the openings 31.

3, at least one of the multiple connective tissue body formation structures 10 is preferably detachably bonded to an adjacent connective tissue body formation structure 10 via a weak adhesive portion 50 having a weaker mechanical strength than the connective tissue body formation structure 10. The weak adhesive portion 50 is provided between adjacent connective tissue body formation structures 10. The bonding strength of the weak adhesive portion 50 bonding adjacent connective tissue body formation structures 10 is weaker than the bonding strength of adjacent connective tissue body formation structures 10 detachably bonded. For example, as shown in FIG. 3, the weak adhesive portion 50 extends along the longitudinal direction L of the support member 20 between the side walls 42a of adjacent storage members 30. The weak adhesive portion 50 is composed of a weak adhesive having a weak adhesive property. For example, from the viewpoints of hardening at room temperature, water resistance and non-toxicity for use in a living body, etc., a silicone-based adhesive is preferable as the weak adhesive. When the connective tissue body formation structure assembly 1 is inserted into a living body, the weak adhesive parts 50 detachably bond the multiple connective tissue body formation structures 10 to such an extent that the multiple connected connective tissue body formation structures 10 do not separate. When a force greater than that during normal activity is applied to the implanted connective tissue body formation structure assembly 1, the multiple connective tissue body formation structures 10 are easily separated from the weak adhesive parts 50. In this way, the cushioning effect caused by the separation of the connective tissue body formation structures 10 is improved, and damage to subcutaneous tissue, skin, etc. can be further suppressed, further improving the stability of the connective tissue body formation structure assembly 1 after implantation.

4, at least one of the multiple connective tissue body formation structures 10 is preferably detachably connected to an adjacent connective tissue body formation structure 10 via a connecting portion 60. The connecting portion 60 is provided between adjacent connective tissue body formation structures 10. The connecting portion 60 extends along the longitudinal direction L of the support member 20 between the side walls 42a of the adjacent storage members 30. One end 60a of the connecting portion 60 is connected to one adjacent storage member 30, and the other end 60b of the connecting portion 60 is connected to the other adjacent storage member 30. The portion 60b of the connecting portion 60, excluding both ends (one end 60a and the other end 60c), is detachably connected to at least one adjacent storage member 30 with a force equal to or less than the bonding force at which the adjacent connective tissue body formation structures 10 are detachably connected. The connecting portion 60 is preferably flexible rather than rigid, and has a shape such as a string or wire. For example, the density of the connecting portion 60 is smaller than the density of the storage member 30. From the standpoint of water resistance, non-toxicity, biodegradability, and biocompatibility, the connecting part 60 is made of a biocompatible resin such as polytetrafluoroethylene or polyether ether ketone, or a highly rust-resistant metal material such as stainless steel, titanium, cobalt, chromium, or nickel-titanium alloy.

When the connective tissue formation structure assembly 1 is inserted into a living body, the connecting portion 60 connects the multiple connective tissue formation structures 10 in a separable manner to the extent that the multiple connected connective tissue formation structures 10 do not separate. When a force greater than that during normal activity is applied to the connective tissue formation structure assembly 1 during implantation, the side wall 42a connected to the portion 60b other than both ends (one end 60a and the other end 60c) of the connecting portion 60 separates, but the connection between both ends (one end 60a and the other end 60c) of the connecting portion 60 and the side wall 42a is maintained. In this state, adjacent connective tissue formation structures 10 can move freely via the connecting portion 60. In other words, even if adjacent connective tissue formation structures 10 are separated by the side wall 42a, they are connected by the connecting portion 60. Therefore, the connective tissue formation structure assembly 1 can be easily removed with a single incision procedure. In this way, the cushioning effect caused by the separation of the connective tissue formation structure 10 is improved, and since the connective tissue formation structure 10 is connected without being separated, the stability of the connective tissue formation structure assembly 1 after implantation and the ease of removal from the living body are further improved.

As shown in FIG. 5, at least one of the structures 10 for forming connective tissue bodies is preferably provided with a groove 70 extending along the longitudinal direction L of the support member 20. At least one of the structures 10 for forming connective tissue bodies is detachably connected to the adjacent structures 10 for forming connective tissue bodies via the groove 70. The groove 70 is provided on the side between the adjacent structures 10 for forming connective tissue bodies. For example, as shown in FIG. 5, the groove 70 extends along the longitudinal direction L of the support member 20 on the side between the adjacent structures 30 for forming connective tissue bodies, in other words, on the side including the two side walls 42a that are detachably connected to each other, when the structures 10 for forming connective tissue bodies are adjacent to each other. The groove 70 is provided on each of the two opposing side surfaces between the adjacent structures 30. For example, when the structure assembly 1 for forming connective tissue bodies has the above-mentioned weakly adhesive portion 50, the groove 70 is provided on the side including the two side walls 42a (including the weakly adhesive portion 50 in some cases). When the connective tissue body formation structure assembly 1 has a groove provided on the side between adjacent connective tissue body formation structures 10, the connective tissue body formation structure 1 that is subjected to a force greater than that during normal activity during implantation can be separated into connective tissue body formation structures 10 starting from the groove 70. In this way, the cushioning effect caused by the separation of the connective tissue body formation structures 10 is improved, and damage to subcutaneous tissue, skin, etc. can be further suppressed, further improving the stability of the connective tissue body formation structure assembly 1 after implantation.

In addition, in the above-mentioned connective tissue formation structure assembly 1, it is preferable that all of the connective tissue formation structures 10 are detachably connected to adjacent connective tissue formation structures 10. When all of the adjacent connective tissue formation structures 10 are detachably connected to each other, the ease of insertion of the connective tissue formation structure assembly 1 into a living body and the stability after implantation in a living body are further improved.

6 and 7, at least one of the multiple connective tissue body formation structures 10 is preferably movably connected to an adjacent connective tissue body formation structure 10, and more preferably movably connected to an adjacent connective tissue body formation structure 10 in a separable manner. For example, as shown in FIG. 6 and FIG. 7, the adjacent multiple connective tissue body formation structures 10 are movably connected or separably connected to adjacent edges 421a or edges 421b on the same side of the side wall 42a of the storage member 30, which extend along the longitudinal direction L of the support member 20. In the adjacent side walls 42a, not both the edges 421a and the edges 421b adjacent to each other on the same side are connected, but only one of the edges 421a or the edges 421b is connected. In FIG. 6, the multiple connective tissue body formation structures 10 are connected only by the edges 421a, and in FIG. 7, the multiple connective tissue body formation structures 10 are alternately connected by the edges 421a and the edges 421b.

When adjacent connective tissue body formation structures 10 are movably connected or detachably connected, it becomes easier to insert the connective tissue body formation structure assembly 1 into the subcutaneous tissue. In addition, since the connective tissue body formation structures 10 constituting the connective tissue body formation structure assembly 1 are movable, damage to the subcutaneous tissue and the like caused by the connective tissue body formation structure assembly 1 during implantation is further suppressed, and the adhesion between the connective tissue body formation structure assembly 1 and the living body during implantation is further improved. In some cases, even if the connective tissue body formation structure assembly 1 during implantation receives a large force from the living body, the connective tissue body formation structure assembly 1 is not separated by the movement of the connective tissue body formation structure 10, so the connective tissue body formation structure assembly 1 can be easily removed. In this way, the ease of insertion and removal of the connective tissue body formation structure assembly 1, as well as the stability after implantation, are further improved.

8, at least one of the multiple connective tissue body formation structures 10 is detachably connected to an adjacent connective tissue body formation structure 10 via a movable part 80. The movable part 80 is provided between adjacent connective tissue body formation structures 10. For example, as shown in FIG. 8, the movable part 80 extends along the longitudinal direction L of the support member 20 between the edges 421a of the side walls 42a of adjacent storage members 30. For example, the movable part 80 may have a hinge structure or may be an elastic body. The adjacent connective tissue body formation structures 10 are rotatably connected with the movable part 80 as the center of rotation.

In addition, it is preferable that all of the connective tissue body formation structures 10 are movably connected to adjacent connective tissue body formation structures 10, and it is more preferable that they are detachably movably connected to adjacent connective tissue body formation structures 10. When all of the adjacent connective tissue body formation structures 10 are movably connected or detachably movably connected to each other, the ease of insertion and removal of the connective tissue body formation structure assembly 1, as well as the stability after implantation, are further improved.

9, among the multiple connective tissue formation structures 10 arranged in parallel, at least one end corner 44 of the container member 30a constituting the connective tissue formation structure 10a arranged at the end is preferably provided with a corner inclined surface 45 connecting the adjacent end side surface 42b and end surface 43 between the adjacent end side surface 42b and end surface 43. The end side surface 42b of the container member 30a arranged at the end constitutes the side surface of the outer edge of the connective tissue formation structure assembly 1. The corner inclined surface 45 connects to the adjacent end side surface 42b and end surface 43 of the container member 30a at an angle of 90 degrees or more. The end corner 44 having the corner inclined surface 45 is not a right-angled shape like the end corner 44 not having the corner inclined surface 45, but is a chamfered surface connecting to the end side surface 42b and end surface 43 of the container member at an angle of 90 degrees or more. Here, the corner inclined surface 45 is flat, but it may be curved, or may have a shape that is a mixture of flat and curved surfaces.

When the sheet-shaped connective tissue formation structure assembly 1 is inserted into the living body from the terminal corner 44 having the corner inclination surface 45, the corner inclination surface 45 is located at the front side in the insertion direction of the connective tissue formation structure assembly 1. When the sheet-shaped connective tissue formation structure assembly 1 is inserted into the living body, the connective tissue formation structure assembly 1 is prevented from catching on the subcutaneous tissue, skin, subcutaneous tissue, and parts where the skin has not been peeled off, particularly the terminal corner 44 having the corner inclination surface 45, so that the operability of the connective tissue formation structure assembly 1 during insertion is improved. In particular, as shown in FIG. 9, when the corner inclination surface 45 is provided between the end face facing the end face having the opening 31 and the terminal side surface 42b, the end face 43 connected to the corner inclination surface 45 is smooth, so that the insertion of the connective tissue formation structure assembly 1 into the living body becomes even easier. In addition, damage to the skin and subcutaneous tissue caused by the inclined corner surface 45 of the connective tissue formation structure assembly 1 during implantation can be suppressed, further improving the stability of the connective tissue formation structure assembly 1 after implantation.

The angle α between the corner inclined surface 45 and the terminal side surface 42b, and the angle β between the corner inclined surface 45 and the end surface 43 are preferably greater than 90 degrees and less than 180 degrees, and it is more preferable that the angles α and β are both 135 degrees. When the angles α and β are within the above ranges, the terminal corner 44 having the corner inclined surface 45 is further prevented from getting caught when the connective tissue formation structure assembly 1 is inserted, and damage to subcutaneous tissue, etc. caused by the terminal corner 44 having the corner inclined surface 45 during the implantation of the connective tissue formation structure assembly 1 is further suppressed, thereby further improving the ease of insertion of the connective tissue formation structure assembly 1 and the stability after implantation.

Also, as shown in FIG. 10, it is preferable that the corner inclined surface 45 is provided on two end corners 44. Here, the corner inclined surface 45 is provided between the end face facing the end face having the opening 31 and each end side surface 42b. In this way, for the connective tissue formation structure assembly 1 having the corner inclined surface 45 on the multiple end corners 44, in addition to insertion from the end corner 44 having the corner inclined surface 45, even if it is inserted into the living body from the end face 43 sandwiched between the two adjacent corner inclined surfaces 45, the end face 43 and the two corner inclined surfaces 45 become the front surface in the insertion direction of the connective tissue formation structure assembly 1, and the connective tissue formation structure assembly 1 is prevented from getting caught during insertion, making it even easier to insert the connective tissue formation structure assembly 1 into the living body. In addition, since the corner inclined surface 45 is provided on the multiple end corners 44, damage to subcutaneous tissue and the like is further suppressed, and the stability of the connective tissue formation structure assembly 1 after implantation is further improved.

As shown in FIG. 11, it is more preferable that the corner inclined surface 45 is provided on three end corners 44. Here, the corner inclined surface 45 is provided between the end face facing the end face with the opening 31 and each end side 42b, and between the end face with the opening 31 and the end side 42b. In this way, for a connective tissue formation structure assembly 1 having corner inclined surfaces 45 on three adjacent end corners 44, when the embedded connective tissue formation structure assembly 1 is removed from the living body from the corner inclined surface 45 on the rear side in the insertion direction and the end face side with the opening 31, the end corner 44 having the rear side corner inclined surface 45 is prevented from getting caught. Therefore, the operability of the connective tissue formation structure assembly 1 when removing it from the living body is improved. In addition, since the number of end corners 44 having corner inclined surfaces 45 is increased, damage to subcutaneous tissue and the like during implantation is further suppressed.

As shown in FIG. 12, it is more preferable that the corner inclined surfaces 45 are provided on the four terminal corners 44. In this manner, for the connective tissue formation structure assembly 1 having the corner inclined surfaces 45 on all terminal corners 44, the connective tissue formation structure assembly 1 is prevented from getting caught no matter from which direction the connective tissue formation structure assembly 1 is inserted into or removed from the living body. This makes it even easier to insert the connective tissue formation structure assembly 1 into and remove it from the living body. In addition, since all terminal corners 44 have the corner inclined surfaces 45, damage to subcutaneous tissue and the like during implantation is further suppressed.

As shown in FIG. 13, it is preferable that the corner inclined surfaces 45 provided on the adjacent terminal corners 44 are connected to each other. Here, the corner inclined surfaces 45 are provided between the end face facing the end face with the opening 31 and each terminal side surface 42b, and the two corner inclined surfaces 45 are connected to each other. The end face facing the end face with the opening 31 is substantially composed of two corner inclined surfaces 45. When the connective tissue formation structure assembly 1 having the corner inclined surfaces 45 that are continuously connected to each other is inserted into the living body from the two corner inclined surfaces 45, the connective tissue formation structure assembly 1 is prevented from getting caught when the connective tissue formation structure assembly 1 is inserted, making it even easier to insert the connective tissue formation structure assembly 1 into the living body. In addition, since the corner inclined surfaces 45 are provided on the multiple terminal corners 44, damage to subcutaneous tissue and the like during implantation is further suppressed.

In addition, in the connective tissue formation structure assembly 1 shown in FIG. 13, the angle a between the two corner inclined surfaces 45 is preferably greater than 90 degrees and less than 180 degrees, and more preferably greater than 120 degrees and less than 180 degrees. When the angle a is within the above range, the ease of insertion and removal of the connective tissue formation structure assembly 1, as well as the stability after implantation, are further improved.

As shown in FIG. 14, it is preferable that the terminal corner 44 having the corner inclined surface 45 has a convex curved sidewall inclined surface 46 between the corner inclined surface 45 and the side surface 42c, which connects the corner inclined surface 45 and the side surface 42c. The side surface 42c of the housing member 30a is a side surface that connects to the terminal side surface 42b. The sidewall inclined surface 46 is a chamfered surface that connects to the corner inclined surface 45 and the side surface 42c at an angle of 90 degrees or more. When the connective tissue formation structure assembly 1 has the sidewall inclined surface 46 in this way, the connective tissue formation structure assembly 1 is further prevented from getting caught and from causing damage to subcutaneous tissue, etc. during implantation.

As shown in FIG. 15, it is preferable that a covering portion 90 made of a material softer than the housing member 30 is provided on at least the inclined corner surface 45 of the housing member 30. When the connective tissue formation structure assembly 1 is provided with the covering portion 90 in this manner, even if the terminal corner portion 44 having the inclined corner surface 45 gets caught on the living body, damage to the living body is suppressed, and damage to the subcutaneous tissue during implantation is further suppressed.

Next, a method for forming a connective tissue body according to an embodiment will be described. The method for forming a connective tissue body according to an embodiment includes a step (S-1) of inserting and embedding the connective tissue body formation structure assembly 1 described above into a living body other than a human, a step (S-2) of forming a connective tissue body in the connective tissue body formation space 32 of the connective tissue body formation structure assembly 1 embedded in the living body, and a step (S-3) of removing the connective tissue body formation structure assembly 1 containing the connective tissue body formed in the connective tissue body formation space 32 from the living body.

In step (S-1), the connective tissue body formation structure assembly 1 is inserted into a predetermined site in a non-human living body, thereby embedding the connective tissue body formation structure assembly 1 in the living body. The connective tissue body formation structure assembly 1 is embedded in subcutaneous tissue of the limbs, shoulders, back, abdomen, etc. As an example, part of the skin, such as the epidermis and dermis, which cover the subcutaneous tissue from the outside, is peeled from the living body, the connective tissue body formation structure assembly 1 is inserted into the subcutaneous tissue, and the partially peeled skin is sutured to the living body, thereby embedding the connective tissue body formation structure assembly 1 in the subcutaneous tissue.

In step (S-2) carried out after step (S-1), the connective tissue body forming structure assembly 1 is embedded in a living body for a predetermined time, and a hollow cylindrical connective tissue body is formed in the connective tissue body formation space 32 of the connective tissue body forming structure assembly 1. During the embedding of the connective tissue body forming structure assembly 1, the connective tissue in the living body enters the connective tissue body formation space 32 from the communication part 33 of the connective tissue body forming structure assembly 1, and the connective tissue in the connective tissue body formation space 32 grows, forming a connective tissue body in the connective tissue body formation space 32. The connective tissue body is composed of fibroblasts and an extracellular matrix such as collagen.

In step (S-3) performed after step (S-2), the connective tissue body formation structure assembly 1 containing the connective tissue formed in the connective tissue body formation space 32 is removed from the living body. In some cases, a plurality of separated connective tissue body formation structures 10 are removed as the connective tissue body formation structure assembly 1. When the connective tissue formed in the connective tissue body formation space 32 is bonded to biological tissue present around the connective tissue body formation structure assembly 1 (connective tissue body formation structure 10), the surrounding biological tissue and the connective tissue body formation structure assembly 1 are cut, and the connective tissue body formation structure assembly 1 is removed from the living body.

In step (S-3), it is preferable to remove each connective tissue body formation structure 10 constituting the connective tissue body formation structure assembly 1 from one removal part. One removal part is easily formed in the living body by one incision treatment. The removal part is provided as a mark for the location of the insertion part used when the connective tissue body formation structure assembly 1 is inserted into the living body in step (S-1). When multiple connective tissue body formation structures 10 are not separated or when multiple connective tissue body formation structures 10 are connected via the connection part 60 shown in FIG. 4, the connective tissue body formation structure assembly 1 can be removed from one removal part. Even if the connective tissue body formation structures 10 are separated, all the connective tissue body formation structures 10 continue to be embedded in one part of the living body, so that all the connective tissue body formation structures 10 can be removed from one removal part. In this way, the connective tissue formation structure assembly 1 and the connective tissue formation structure 10 are continuously embedded in one location within the living body, so that the connective tissue formation structure assembly 1 and the connective tissue formation structure 10 can be easily removed from one removal site without providing multiple removal sites.

The method for forming a connective tissue body according to the embodiment may further include, after step (S-3), a step (S-4) of separating the connective tissue body from the connective tissue body formation space 32 of the connective tissue body formation structure assembly 1 (connective tissue body formation structure 10) removed from the living body. In step (S-4) performed after step (S-3), the connective tissue body is separated from the connective tissue body formation space 32 of the connective tissue body formation structure assembly 1 removed from the living body to obtain a cylindrical connective tissue body. When the connective tissue is formed on the outer surface of the connective tissue body formation structure assembly 1, the connective tissue is removed from the outer surface of the connective tissue body formation structure assembly 1, and then the connective tissue body is separated from the connective tissue body formation space 32.

When the obtained connective tissue is to be used for xenotransplantation into humans, etc., it is preferable to subject the connective tissue to immunogen removal treatments such as decellularization, dehydration, and fixation in order to prevent rejection after transplantation. Decellularization treatments include methods in which the extracellular matrix is eluted and washed by ultrasonic treatment, surfactant treatment, and enzyme treatment such as collagenase. Dehydration treatments include methods in which the tissue is washed with a water-soluble organic solvent such as methanol, ethanol, and isopropyl alcohol. Fixation treatments include methods in which the tissue is treated with an aldehyde compound such as glutaraldehyde or formaldehyde.

According to the embodiment described above, the multiple connective tissue body formation structures 10 are detachably connected to each other, and the configuration of the multiple connective tissue body formation structures 10 constituting the connective tissue body formation structure assembly 1 is optimized, so that the connective tissue body formation structure assembly 1 can be suitably embedded in a living body larger than a human. Furthermore, the connective tissue body formation structure assembly 1 has good at least one of the following: ease of insertion into the living body, ease of removal from the living body, stability after implantation in the living body, and productivity of the connective tissue body.

In the above, an example in which the support member 20 is cylindrical has been shown, but the support member 20 may be a square tube. In this case, the shape of the inner surface 41 of the storage member 30 is appropriately set according to the outer shape of the support member 20 so that the distance d between the side surface 21 of the support member 20 and the inner surface 41 of the storage member 30 is constant.

In addition, in the above, an example has been shown in which the other end of the support member 20 is connected to the inside of the end wall of the storage member 30, but one end of the support member 20 may be connected to the inner surface 34b of the lid portion 34. In this case, the other end of the support member 20 may or may not be connected to the inside of the end wall of the storage member 30.

In addition, in the above example, the communication portion 33 is provided on one side wall 42 of each storage member 30, but the communication portion 33 may be provided on multiple side walls 42 of each storage member 30.

In the above, as shown in FIG. 5, an example has been shown in which the groove portion 70 extends over the entire length of the support member 20 in the longitudinal direction L. However, as long as the stability of the connective tissue formation structure assembly 1 after implantation is not reduced, the groove portion 70 may extend, for example, partially along the longitudinal direction L of the support member 20. In addition, the groove portion 70 may be provided on both opposing sides as shown in FIG. 5, or may be provided on only one side.

In the above, an example was shown in which the outer shape of the storage member 30 is a rectangular tube, but the configuration of the storage member 30 may be such that cylindrical storage members 30 are arranged as shown in FIG. 16, that triangular tube-shaped storage members 30 are arranged in parallel as shown in FIG. 17, or that triangular tube-shaped storage members 30 are arranged alternately upside down as shown in FIG. 18.

In addition, in the above, as shown in FIG. 7, examples are shown in which multiple connective tissue body formation structures 10 are regularly and alternately joined at the edges 421a and 421b, but multiple connective tissue body formation structures 10 may be irregularly joined at the edges 421a and 421b. The joining arrangement of the connective tissue body formation structures 10 by the edges 421a and 421b can be appropriately set according to the shape inside the living body.

In the above, as shown in FIG. 14, an example in which the terminal corner 44 has one sidewall inclined surface 46 has been shown, but the terminal corner 44 may have two sidewall inclined surfaces. In this case, the two sidewall inclined surfaces face each other via the corner inclined surface 45. When the terminal corner 44 has two sidewall inclined surfaces, the connective tissue formation structure assembly 1 is further prevented from getting caught and damage to the subcutaneous tissue during implantation is further suppressed.

Also, as shown in FIG. 19, a cover tube 23 extending along the longitudinal direction L may be provided on the side surface 21 of the support member 20. The cover tube 23 is cylindrical and covers the periphery of the side surface 21 of the support member 20. As with the support member 20, one end of the cover tube 23 may protrude from the opening 31 of the storage member 30.

The lid 34 may also have one or more through holes that connect the connective tissue body formation space 32 to the outside of the connective tissue body formation structure 10. Connective tissue enters the connective tissue body formation space 32 from the outside of the connective tissue body formation structure 10 via the communication portion 33 and the through holes, so that a good cylindrical connective tissue body can be easily formed within the connective tissue body formation space 32.

At least one of the four corners of the lid 34 may be curved. When the connective tissue body formation structure assembly 1 is inserted into the living body from the curved corner of the lid 34, the operability of the connective tissue body formation structure assembly 1 during insertion is improved. In addition, the curved corner of the lid 34 of the connective tissue body formation structure assembly 1 during implantation can be suppressed from causing damage to the skin and subcutaneous tissue, so that the stability of the connective tissue body formation structure assembly 1 after implantation is further improved. From the viewpoint of improving the operability of the connective tissue body formation structure assembly 1 during insertion and the stability of the connective tissue body formation structure assembly 1 after implantation, it is preferable that one corner of the lid 34 is curved, more preferably two corners are curved, even more preferably three corners are curved, and most preferably all corners are curved.

Although the embodiments have been described above, the present invention is not limited to the above embodiments, but includes all aspects included in the concept and claims of this disclosure, and can be modified in various ways within the scope of this disclosure.

LIST OF SYMBOLS 1 Structural assembly for forming connective tissue body 10 Structure for forming connective tissue body 10a Structure for forming connective tissue body arranged at end 20 Support member 21 Side surface of support member 22 End surface of support member 23 Cover tube 30 Storage member 30a Storage member arranged at end 31 Opening 32 Connective tissue body formation space 33 Communication portion 34 Lid portion 34a Surface for easy separation of lid portion 34b Inner surface of lid portion 41 Inner surface of storage member 42, 42a Side wall of storage member 421a, 421b Edge of side wall of storage member 42b End side surface of storage member 42c Side surface of storage member 43 End surface of storage member 44 End corner portion 45 Corner inclined surface 46 Side wall inclined surface 50 Weakly bonded portion 60 Connection portion 60a One end of connection portion 60b Portion excluding both ends of connection portion 60c: other end of connecting portion 70: groove portion 80: movable portion 90: covering portion L: longitudinal direction of supporting member

Claims (13)

A plurality of connective tissue formation structures each having a tubular support member and a housing member for housing the support member,
The plurality of connective tissue formation structures are arranged in parallel,
At least one of the plurality of connective tissue formation structures is detachably connected to an adjacent one of the connective tissue formation structures during implantation in a living body;
A connective tissue formation space capable of forming a connective tissue is provided between the support member and the inner surface of the storage member,
A structure assembly for connective tissue formation, characterized in that the container member is provided with a communication part that communicates the connective tissue formation space with the outside of the structure for connective tissue formation. The connective tissue formation structure assembly according to claim 1, wherein the multiple connective tissue formation structures are arranged two-dimensionally. The connective tissue formation structure assembly according to claim 1 or 2, wherein at least one of the multiple connective tissue formation structures is detachably bonded to an adjacent connective tissue formation structure via a weak adhesive portion. The connective tissue formation structure assembly according to claim 1 or 2, wherein at least one of the multiple connective tissue formation structures is detachably connected to an adjacent connective tissue formation structure via a connecting portion. The structure assembly for forming connective tissue according to claim 4, wherein the density of the connecting portion is less than the density of the containing member. The connective tissue formation structure assembly according to any one of claims 1 to 5, wherein at least one of the plurality of connective tissue formation structures has a groove extending along the longitudinal direction of the support member. The connective tissue formation structure assembly according to any one of claims 1 to 6, wherein all of the connective tissue formation structures are detachably connected to adjacent connective tissue formation structures. The connective tissue formation structure assembly according to any one of claims 1 to 7, wherein at least one of the multiple connective tissue formation structures is movably connected to an adjacent connective tissue formation structure. The connective tissue formation structure assembly according to any one of claims 1 to 8, wherein all of the connective tissue formation structures are movably connected to adjacent connective tissue formation structures. The connective tissue formation structure assembly according to any one of claims 1 to 9, wherein at least one end corner of the container member constituting the connective tissue formation structure arranged at the end among the multiple connective tissue formation structures arranged in parallel is provided with a corner inclined surface connecting the adjacent end side surface and end surface between the adjacent end side surface and end surface. The connective tissue formation structure assembly according to claim 10, wherein a covering made of a material softer than the housing member is provided on at least the inclined corner surface of the housing member. A step (S-1) of inserting and implanting the connective tissue formation structure assembly according to any one of claims 1 to 11 into a living body other than a human;
A step (S-2) of forming a connective tissue in the connective tissue formation space of the connective tissue formation structure assembly implanted in the living body;
A method for forming a connective tissue body, comprising a step (S-3) of removing the connective tissue body formation structure assembly containing the connective tissue body formed in the connective tissue body formation space from the living body. The method for forming a connective tissue body according to claim 12, wherein in the step (S-3), each of the structures for connective tissue body formation constituting the connective tissue body formation structure assembly is taken out from one take-out section.

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