Structure for forming connective tissue body and method for forming connective tissue body

Abstract

To provide a structure for a connective tissue body formation which is used by being implanted into a living body other than a human and is excellent in at least one of easiness of insertion into a living body, stability after implanting into the living body and productivity of a connective tissue body, and method for forming a connective tissue body.SOLUTION: A structure for a connective tissue body formation includes a plate member group provided with a plurality of rectangular plate members which are oppositely separated, and at least one separation member provided among the plurality of plate members to oppositely separating the plurality of plate members, at least one corner part of each plate member is provided with an inclined plane for connecting two adjacent side surfaces between the two adjacent side surfaces of each plate member, the plurality of plate members are oppositely separated from one another in parallel, and a connective tissue body formation space in which a connective tissue body can be formed, and at least one communication part for communicating the connective tissue body formation space with the outside of the structure for a connective tissue body formation are provided among the plurality of plate members.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to a structure for forming a connective tissue structure and a method for forming a connective tissue structure. [Background technology]

[0002] In recent years, there has been active research into regenerative medicine, which aims to restore the functions of cells, tissues, organs, etc. lost due to illness or accidents using artificial materials and cells.

[0003] For example, when a foreign body penetrates deep inside a living body, fibroblasts gradually gather around the foreign body, forming a connective tissue structure mainly composed of fibroblasts and collagen, etc. Using this reaction, technology is being researched to form a connective tissue structure by implanting a foreign body in the living body.

[0004] For example, Patent Document 1 describes a substrate for forming a membranous connective tissue body, which can be placed in an environment where biological tissue material is present and can form a membranous connective tissue body on its surface, in which two tissue formation surfaces for forming connective tissue are arranged opposite each other across a tissue formation space so that both sides of the membranous connective tissue body are formed to match the surface of the substrate, and at least one of the tissue formation surfaces has multiple types of slits formed therein that connect the tissue formation space with the outside of the substrate, and the longitudinal directions of the various slits are set in different directions.

[0005] Patent document 2 also describes a substrate for forming a membranous connective tissue body, which can be placed in an environment where biological tissue material is present to form a membranous connective tissue body on its surface, and which has two connective tissue forming surfaces arranged opposite each other so that both sides of the membranous connective tissue body are formed to fit the substrate surface.

[0006] Patent documents 1 and 2 describe a method in which a substrate for forming a connective tissue body is implanted as a foreign body in a living body such as a human or placed in a culture device, a connective tissue body is formed inside the substrate for forming a connective tissue body, and then the substrate for forming a connective tissue body is removed from the living body or the culture device to obtain the connective tissue body.

[0007] When forming connective tissue bodies in the human body, so-called autotransplantation or allotransplantation, it is necessary to perform a procedure of incising and inserting a substrate for forming a connective tissue body into the human body, a procedure of suturing the incision after insertion, a procedure of incising again and taking out the substrate for forming a connective tissue body from the body after the formation of the connective tissue body, and a procedure of suturing the incision again, which places a heavy burden on the human body due to multiple procedures.In addition, since the substrate for forming a connective tissue body is embedded in the human body, it is difficult to increase the size and amount of the substrate for forming a connective tissue body, and it is difficult to mass-produce connective tissue bodies by one embedding of the substrate for forming a connective tissue body.

[0008] In addition, as a powerful means for mass-producing connective tissue bodies, the use of a large connective tissue body forming substrate to prepare a sheet-like connective tissue body with a large area has been considered. In the case of a cylindrical connective tissue body forming substrate as in Patent Document 1, even when a large animal is used, a gap occurs between the cylindrical connective tissue body forming substrate and the living body during implantation, and it is difficult to easily adhere to the living body, making it difficult to prepare a sheet-like connective tissue body with a large area. In addition, since the connective tissue body formed with the cylindrical connective tissue body forming substrate is cylindrical, there is a difference in area between the inner and outer surfaces of the cylindrical connective tissue body, and the physical properties of the front and back surfaces of the sheet-like connective tissue body obtained by cutting the cylindrical connective tissue body in the longitudinal direction may differ, and the sheet-like connective tissue body may tend to curl in a specific direction. In particular, when the sheet-like connective tissue body has a large area, the difference in physical properties between the front and back surfaces becomes significant, and the quality of the sheet-like connective tissue body is likely to vary. In addition, when the cylindrical connective tissue body forming substrate is large, the living body needs to be incised into a large cylindrical shape, so the incision procedure is not easy and the burden on the living body is large.

[0009] Furthermore, it is difficult to control the behavior of animals other than humans, especially large animals, during movement and exercise. For example, animals such as cows, horses, pigs, and goats generate a large force when walking, so that a part of the substrate for forming a connective tissue body during implantation may break through the skin of the large animal and go out, and if the part of the substrate for forming a connective tissue body that has gone out gets caught on a fence in a ranch and the animal walks, 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 substrate for forming a membranous connective tissue body such as that in Patent Document 2 is used, the end of the substrate for forming a membranous connective tissue body is sharper than that of a cylindrical substrate for forming a connective tissue body, and in addition, the substrate for forming a membranous connective tissue body during implantation is likely to adhere to the living body, so that problems such as the above-mentioned skin tearing are likely to occur, and it may be difficult to grow the connective tissue body or maintain the quality of the connective tissue body.

[0010] Furthermore, when a connective tissue structure is formed using a culture device, very expensive equipment is required compared to a method in which a substrate for forming a connective tissue structure is implanted in a living body. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] JP 2017-113051 A [Patent Document 2] JP 2014-030598 A Summary of the Invention [Problem to be solved by the invention]

[0012] The object of the present disclosure is to provide a structure 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 has excellent at least one of ease of insertion into the body, stability after implantation in the body, and productivity of the connective tissue body. [Means for solving the problem]

[0013] [1] A structure for forming connective tissue bodies comprising a plate member group having a plurality of rectangular plate members facing each other and spaced apart, and at least one spacer member provided between the plate members constituting the plate member group and spaced apart the plate members facing each other, wherein at least one corner of each of the plate members is provided with an inclined surface connecting two adjacent side surfaces of each of the plate members, the plate members are parallel to each other and spaced apart, and between the plate members there is provided a connective tissue body formation space extending in the in-plane direction of the plate members and capable of forming connective tissue bodies, and at least one communication portion connecting the connective tissue body formation space and the outside of the structure for forming connective tissue bodies. [2] The structure for forming connective tissue described in [1] above, wherein in a cross section of the plate member parallel to the in-plane direction of the plate member, the angle between the inclined surface and each of the side surfaces connected to the inclined surface is greater than 90 degrees and less than 180 degrees. [3] The connective tissue formation structure described in [2] above, wherein the inclined surface is flat. [4] The connective tissue formation structure described in [2] above, wherein the inclined surface is curved, and in a cross section of the plate member parallel to the in-plane direction of the plate member, the inclined surface is arc-shaped. [5] The connective tissue formation structure according to any one of the above [1] to [4], wherein the inclined surfaces are provided at a plurality of adjacent corners of each of the plate members. [6] The connective tissue formation structure according to any one of the above [1] to [5], wherein the inclined surfaces are provided at all corners of each of the plate members. [7] The connective tissue formation structure described in [5] or [6] above, wherein the inclined surfaces provided at the adjacent corners are connected to each other. [8] A connective tissue formation structure described in any one of [1] to [7] above, wherein a connective tissue formation promoting substance that promotes the formation of connective tissue is provided on one of the two opposing inner surfaces of the plurality of plate members. [9] A structure for forming a connective tissue body described in any one of [1] to [8] above, wherein, among the plurality of plate members constituting the plate member group, the outer surface of one plate member arranged on the outermost side is convexly curved, and the outer surface of the other plate member arranged on the outermost side is flat.

[10] A structure for forming a connective tissue body according to any one of [1] to [9] above, wherein a corner portion having the inclined surface in one of the plate members arranged on the outermost side among the plurality of plate members constituting the plate member group is provided with a convex curved outer inclined surface connecting the inclined surface and the outer surface between the inclined surface and the outer surface of the plate member.

[11] The connective tissue formation structure according to any one of the above [1] to

[10] , wherein a covering portion made of a material softer than the plate member is provided on at least the inclined surface of the plate member.

[12] A method for forming a connective tissue body, comprising the steps of: (S-1) inserting and embedding a connective tissue body formation structure described in any one of [1] to

[11] above into a living body 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 embedded in the living body; and (S-3) removing the connective tissue body formation structure containing the connective tissue body formed in the connective tissue body formation space from the living body.

[13] The method for forming a connective tissue body described in

[12] above, further comprising, prior to the step (S-1), a step (SA) of providing an insertion part into a living body other than a human, into which the connective tissue body formation structure can be inserted, and in the step (S-1), the connective tissue body formation structure is inserted through the insertion part and embedded. Effect of the Invention

[0014] According to the present disclosure, it is possible to provide a connective tissue formation structure and a method for forming a connective tissue structure that can be implanted into a living body other than a human, and that has excellent at least one of ease of insertion into the body, stability after implantation in the body, and productivity of the connective tissue body. [Brief description of the drawings]

[0015] [Figure 1] FIG. 1 is a perspective view showing an example of a connective tissue formation structure according to an embodiment. [Diagram 2] FIG. 2 is a cross-sectional view taken along line AA of FIG. [Diagram 3] FIG. 3 is a perspective view showing an example of an inclined surface constituting the connective tissue formation structure of the embodiment. [Figure 4] FIG. 4 is a cross-sectional view taken along line BB of FIG. [Diagram 5] FIG. 5 is a perspective view showing an example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 6] FIG. 6 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 7] FIG. 7 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 8] FIG. 8 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 9] FIG. 9 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 10] FIG. 10 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 11] FIG. 11 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 12] FIG. 12 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 13] FIG. 13 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 14] FIG. 14 is a perspective view showing an example of an inclined surface constituting the connective tissue formation structure of the embodiment. [Figure 15] FIG. 15 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 16]FIG. 16 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. [Figure 17] FIG. 17 is a perspective view showing another example of a plate member constituting the connective tissue formation structure of the embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] Hereinafter, a detailed description will be given based on an embodiment.

[0017] As a result of extensive research, the researchers have discovered that by optimizing the shape and arrangement of the multiple plate members that make up the connective tissue body formation structure, the connective tissue body formation structure can be used in living organisms other than humans, and that it is superior in at least one of the following: ease of insertion into the body, stability after implantation in the body, and productivity of the connective tissue body; and have completed the present disclosure based on this finding.

[0018] The connective tissue body formation structure of one embodiment comprises a plate member group having a plurality of rectangular plate members facing each other and spaced apart, and at least one spacing member arranged between the plate members constituting the plate member group and spacing the plate members facing each other, at least one corner of each plate member is provided with an inclined surface connecting two adjacent side surfaces of each plate member, the plate members are parallel to each other and spaced apart, and between the plate members there is provided a connective tissue body formation space extending in the in-plane direction of the plate members and capable of forming connective tissue bodies, and at least one communication portion connecting the connective tissue body formation space and the outside of the connective tissue body formation structure.

[0019] Fig. 1 is a perspective view showing an example of a connective tissue formation structure of an embodiment, and Fig. 2 is a cross-sectional view taken along line AA in Fig. 1. Specifically, Fig. 2 is a cross-sectional view of the plate member 10 parallel to an in-plane direction L of the plate member 10.

[0020] As shown in FIG. 1, the connective tissue formation structure 1 has a plate member group 100 and a spacing member 20. The plate member group 100 includes a plurality of plate members 10. The plate members 10 constituting the plate member group 100 are rectangular and face each other at a distance. At least one spacing member 20 is provided between the plurality of plate members 10. The spacing member 20 is connected to the main surface of the plate member 10 and faces and spaces the plurality of plate members 10. For example, four spacing members 20 are provided between two closely facing plate members 10, near all corners 11 of the plate members 10. For example, the spacing members 20 are cylindrical.

[0021] A connective tissue formation space 30 is provided between the multiple plate members 10. The connective tissue formation space 30 provided between each plate member 10 extends in a sheet shape along the in-plane direction L of the multiple plate members 10. The connective tissue formation space 30 is a space in which a connective tissue can be formed.

[0022] Furthermore, at least one communication part 40 is provided between the multiple plate members 10 on the outer edge side of the plate members 10. The communication part 40 provided between each plate member 10 communicates the connective tissue body formation space 30 with the outside of the connective tissue body formation structure 1. The communication part 40 opens perpendicularly to the in-plane direction L of the plate member 10. Here, each communication part 40 is composed of two closely opposing plate members 10 and two spacing members 20 provided between each plate member 10.

[0023] As described below, when the connective tissue body formation structure 1 is embedded in a living organism other than a human (hereinafter also simply referred to as a living organism), the connective tissue enters the connective tissue body formation space 30 from the outside of the connective tissue body formation structure 1 through the communication part 40, and a sheet-like connective tissue body is formed in the connective tissue body formation space 30. The connective tissue body is composed of an extracellular matrix such as fibroblasts and collagen. The connective tissue body is used in a sheet or tube 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.

[0024] The material constituting the plurality of plate members 10 and the spacing members 20 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 adversely affect the connective tissue to be formed or the living body, or does not release such substances in large amounts. From this viewpoint, the material constituting the plurality of plate members 10 and the spacing members 20 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 surfaces of the plurality of plate members 10 and the spacing members 20 may 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.

[0025] As shown in FIG. 1 and FIG. 2, at least one corner 11 of each plate member 10 constituting the sheet-like connective tissue formation structure 1 is provided with an inclined surface 12. The inclined surface 12 is between two adjacent side surfaces 13 of each plate member 10 and connects to the two adjacent side surfaces 13. The inclined surface 12 is connected to the two adjacent side surfaces 13 at an angle of more than a right angle. For example, the inclined surface 12 is provided between the first side surface 13a and the second side surface 13b, and connects to the first side surface 13a and the second side surface 13b at an angle of more than a right angle. The multiple plate members 10 having the inclined surfaces 12 are spaced apart and parallel to each other, as shown in FIG. 1. That is, the multiple plate members 10 are spaced apart and opposed to each other in the same direction. Corner 11 with inclined surface 12 is not a right-angled shape like corner 11 without inclined surface 12, but is a chamfered surface that connects to first side surface 13a and second side surface 13b at an angle greater than a right angle.

[0026] The connective tissue formation structure 1 is used by being implanted in a living body other than human. Examples of living bodies other than 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 one implantation, and are widely raised as livestock.

[0027] The connective tissue body formation structure 1 is embedded in the living body in the subcutaneous tissue of the limbs, shoulders, back, abdomen, etc. After a part 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 structure 1 is inserted into the subcutaneous tissue by inserting it, and then the partially peeled skin is sutured to the living body, thereby embedding the connective tissue body formation structure 1 in the subcutaneous tissue. The sheet-like connective tissue body formation structure 1 can be inserted while cutting open the subcutaneous tissue when being inserted. For example, the connective tissue body formation structure 1 is inserted into the living body from an insertion part formed by incising the living body. Since the insertion part into which the sheet-like connective tissue body formation structure 1 is inserted is linear, the insertion part can be formed by a simple incision procedure.

[0028] As described above, the sheet-like connective tissue body formation structure 1 includes a plurality of plate members 10 arranged in parallel and having an inclined surface 12. When the connective tissue body formation structure 1 is inserted into a living body from the corner portion 11 having the inclined surface 12, the inclined surface 12 is located in front of the connective tissue body formation structure 1 in the insertion direction. When the sheet-like connective tissue body formation structure 1 is inserted into a living body, the plate member 10, particularly the corner portion 11 having the inclined surface 12, can be prevented from being caught by the subcutaneous tissue, the skin, the subcutaneous tissue, and the part where the skin is not peeled off, and the like, so that the operability of the sheet-like connective tissue body formation structure 1 during insertion is improved. In addition, even if an active living body collides with an obstacle such as a fence in a pasture during the implantation of the connective tissue body formation structure 1, the corner portion 11 having the inclined surface 12 can prevent the connective tissue body formation structure 1 from breaking through the skin and coming out of the living body, and can also prevent the connective tissue body formation structure 1 from damaging the skin and subcutaneous tissue during implantation. Furthermore, the sheet-like connective tissue formation structure 1 implanted in a living body is easily attached to the living body. Therefore, the connective tissue formation structure 1 can be placed in a stable environment, and a connective tissue with excellent quality can be formed.

[0029] On the other hand, when a conventional connective tissue body forming substrate, particularly a rectangular plate member having no inclined surface at the corner, is embedded in an animal other than a human, the sharp corners of the plate member, such as a right angle or acute angle, are easily caught by the skin or subcutaneous tissue, so that the substrate for forming a connective tissue body is not easily inserted into the living body. In addition, the substrate for forming a connective tissue body during embedding is likely to damage the skin or subcutaneous tissue, and in some cases, the sharp corners may break through the skin, causing at least a part of the substrate for forming a connective tissue body to come out of the living body. If the substrate for forming a connective tissue body breaks through the skin and comes out of the living body, the growth of the connective tissue body becomes insufficient, making it difficult to form a connective tissue body of good quality. In addition, with regard to the conventional cylindrical substrate for forming a connective tissue body, a large gap occurs between the substrate and the living body, and it is not easy to adhere to the living body, so it is not easy to obtain a good connective tissue body. In addition, when embedding the substrate in the subcutaneous tissue in order to insert the cylindrical substrate for forming a connective tissue body, it is necessary to peel off the skin, which is very laborious and time-consuming. When the size of the cylindrical substrate for forming connective tissue structures is increased for mass production of the connective tissue structures, these problems become more pronounced.

[0030] Thus, unlike conventional connective tissue body formation substrates, the connective tissue body formation structure 1 of the embodiment focuses on the shape and arrangement of the plate member. From the viewpoint of improving the productivity of connective tissue bodies, the connective tissue body formation structure 1 is used in a non-human living body and is embedded in subcutaneous tissue. For non-human living bodies, a part of the skin is peeled off and the connective tissue body formation structure 1 is inserted by inserting it into the subcutaneous tissue. By providing an inclined surface 12 at the corner 11, the ease of inserting the connective tissue body formation structure 1 is improved, and by providing an insertion part of the connective tissue body formation structure 1 in a linear shape, it becomes possible to peel off the skin and insert it at the same time while inserting the connective tissue body formation structure 1. In addition, the connective tissue body formation structure 1 having the inclined surface 12 has excellent stability after embedding and can stably form a connective tissue body in the living body.

[0031] 2, the angles α and β between the inclined surface 12 and each side surface 13 (here, the first side surface 13a and the second side surface 13b) connected to the inclined surface 12 are preferably greater than 90 degrees and less than 180 degrees, more preferably at least one of the angles α and β is 135 degrees or more, and most preferably both of the angles α and β are 157.5 degrees. When the angles α and β between the inclined surface 12 and each side surface 13 in the cross section of each plate member 10 are within the above range, the corners 11 having the inclined surface 12 are further prevented from getting caught when the connective tissue body formation structure 1 is inserted, and damage to subcutaneous tissue and the like caused by the corners 11 having the inclined surface 12 during the implantation of the connective tissue body formation structure 1 is further prevented, so that the ease of insertion of the connective tissue body formation structure 1 and the stability after implantation are further improved.

[0032] Moreover, the inclined surface 12 is planar. The planar inclined surface 12 may be composed of one planar portion as shown in Figs. 1 and 2, and is preferably composed of a plurality of planar portions as shown in Figs. 3 and 4. Here, the inclined surface 12 is composed of a first planar portion 12a connected to the first side surface 13a and a second planar portion 12b connected to the second side surface 13b. When the planar inclined surface 12 is composed of a plurality of planar portions as shown in Figs. 3 and 4, the ease of insertion of the connective tissue formation structure 1 and the stability after implantation are further improved.

[0033] When the planar inclined surface 12 is composed of a plurality of planar portions, the angle γ between the plurality of planar portions (here, the first planar portion 12a and the second planar portion 12b) in a cross section of the plate member 10 parallel to the in-plane direction L of the plate member 10 as shown in Fig. 4 is preferably greater than 90 degrees and less than 180 degrees, more preferably greater than 120 degrees and less than 180 degrees, and most preferably 135 degrees. When the angle γ between the plurality of planar portions is within the above range, the ease of insertion of the connective tissue formation structure 1 into a living body and the stability after implantation in a living body are further improved.

[0034] FIG. 5 is a perspective view showing an example of a plate member 10 constituting the connective tissue body formation structure 1. As shown in FIG. 5, the inclined surfaces 12 are preferably provided at a plurality of adjacent corners 11 of each plate member 10. Here, the inclined surfaces 12 are provided at two adjacent corners 11 of each plate member 10, between the first side surface 13a and the second side surface 13b, and between the first side surface 13a and the fourth side surface 13d, respectively. With respect to the connective tissue body formation structure 1 having the inclined surfaces 12 at the adjacent corners 11 in this manner, even if the connective tissue body formation structure 1 is inserted into a living body from the first side surface 13a sandwiched between the two adjacent inclined surfaces 12 in addition to being inserted from the corner 11 having the inclined surface 12, the first side surface 13a and the two inclined surfaces 12 become the front surface in the insertion direction of the connective tissue body formation structure 1, and the connective tissue body formation structure 1 is prevented from getting caught during insertion, so that the ease of insertion of the connective tissue body formation structure 1 is further improved. Furthermore, since the inclined surfaces 12 are provided at the multiple corners 11, damage to the subcutaneous tissue and the like is further suppressed, and the stability of the connective tissue formation structure 1 after implantation is further improved.

[0035] FIG. 6 is a perspective view showing another example of the plate member 10 constituting the connective tissue body formation structure 1. As shown in FIG. 6, it is more preferable that the inclined surface 12 is provided at three adjacent corners 11 of each plate member 10. Here, the inclined surface 12 is provided between the first side surface 13a and the second side surface 13b, between the second side surface 13b and the third side surface 13c, and between the first side surface 13a and the fourth side surface 13d, respectively. In the connective tissue body formation structure 1 having the inclined surface 12 at three adjacent corners 11 in this manner, when the embedded connective tissue body formation structure 1 is taken out from the living body from the inclined surface 12 between the second side surface 13b and the third side surface 13c located on the rear side in the insertion direction, the corners 11 having the inclined surface 12 are prevented from getting caught. Therefore, the operability of the connective tissue body formation structure 1 when it is taken out from the living body is improved. In addition, since the number of corners 11 having the inclined surface 12 is increased, damage to subcutaneous tissue and the like during implantation is further suppressed.

[0036] Fig. 7 is a perspective view showing another example of the plate member 10 constituting the connective tissue body formation structure 1. As shown in Fig. 7, it is more preferable that the inclined surface 12 is provided at all corners 11 of each plate member 10. In this way, for the connective tissue body formation structure 1 having the inclined surface 12 at all corners 11, no matter from which direction the connective tissue body formation structure 1 is inserted into or removed from a living body, the connective tissue body formation structure 1 is prevented from getting caught, so the ease of insertion and removal of the connective tissue body formation structure 1 is further improved. In addition, since the inclined surface 12 is provided at all corners 11, damage to subcutaneous tissue and the like during implantation is further suppressed.

[0037] FIG. 8 is a perspective view showing another example of the plate member 10 constituting the connective tissue body formation structure 1. As shown in FIG. 8, it is preferable that the inclined surfaces 12 provided at the adjacent corners 11 are connected to each other. Here, the inclined surfaces 12 are provided between the first side surface 13a and the second side surface 13b and between the first side surface 13a and the fourth side surface 13d, respectively, and the two inclined surfaces 12 are connected to each other. The first side surface 13a is substantially composed of two inclined surfaces 12. When the connective tissue body formation structure 1 having the inclined surfaces 12 continuously connected to each other is inserted into a living body from the two inclined surfaces 12, the connective tissue body formation structure 1 is prevented from getting caught during insertion of the connective tissue body formation structure 1, making it easier to insert the connective tissue body formation structure 1. In addition, since the inclined surfaces 12 are provided at the multiple corners 11, damage to subcutaneous tissue and the like during implantation is further suppressed.

[0038] Fig. 9 is a perspective view showing another example of the plate member 10 constituting the connective tissue formation structure 1. As shown in Fig. 9, it is preferable that each of the inclined surfaces 12 provided at the adjacent corners 11 is connected only to the inclined surface 12 adjacent to one side. Here, all the corners 11 have inclined surfaces 12, and the inclined surface 12 provided between the first side surface 13a and the second side surface 13b and the inclined surface 12 provided between the first side surface 13a and the fourth side surface 13d are connected to each other, and the inclined surface 12 provided between the third side surface 13c and the second side surface 13b and the inclined surface 12 provided between the third side surface 13c and the fourth side surface 13d are connected to each other. In addition, the inclined surface 12 provided between the first side surface 13a and the second side surface 13b is not connected to the inclined surface 12 provided between the third side surface 13c and the second side surface 13b, and the inclined surface 12 provided between the first side surface 13a and the fourth side surface 13d is not connected to the inclined surface 12 provided between the third side surface 13c and the fourth side surface 13d. The connecting surfaces formed by connecting the two inclined surfaces 12 face each other. In this way, for the connective tissue formation structure 1 having the plate member 10 that is continuously connected to one adjacent inclined surface and not continuously connected to the other inclined surface, no matter from which direction the connective tissue formation structure 1 is inserted into and removed from a living body, the connective tissue formation structure 1 is prevented from getting caught, making the insertion and removal of the connective tissue formation structure 1 smoother. In addition, since all corners 11 are provided with inclined surfaces 12, damage to subcutaneous tissue and the like during implantation is further suppressed.

[0039] 8 and 9, when the inclined surfaces 12 provided at adjacent corners 11 are connected, the angles a and b between the two inclined surfaces 12 in a cross section of the plate member 10 parallel to the in-plane direction L of the plate member 10 are preferably greater than 90 degrees and less than 180 degrees, and more preferably greater than or equal to 120 degrees and less than 180 degrees. When the angles a and b are within the above ranges, the insertion and removal of the connective tissue formation structure 1 becomes easier, and the stability after implantation is further improved.

[0040] FIG. 10 is a perspective view showing another example of the plate member 10 constituting the connective tissue body formation structure 1. As shown in FIG. 10, in a plurality of plate members 10, it is preferable that a connective tissue body formation promoter 50 that promotes the formation of connective tissue bodies is provided on one of the two opposing inner surfaces 10a. Examples of the connective tissue body formation promoter 50 include blood, fat, collagen, gelatin, and substances containing growth factors and the like. When the connective tissue body formation promoter 50 is provided only on one of the two opposing inner surfaces 10a, it becomes easy to distinguish the front and back sides of the sheet-like connective tissue body taken out of the connective tissue body formation structure 1, and product management such as packaging of the connective tissue body is improved.

[0041] FIG. 11 is a perspective view showing another example of the plate member 10 constituting the connective tissue body formation structure 1. As shown in FIG. 11, it is preferable that, among the multiple plate members 10 constituting the plate member group 100, the outer surface 101b of one plate member 101 arranged on the outermost side is convexly curved, and the outer surface 102b of the other plate member 102 arranged on the outermost side is flat. The convex curved surface of the outer surface 101b protrudes toward the outside of the connective tissue body formation structure 1 in a direction away from the in-plane direction L of the plate member 10. When the connective tissue body formation structure 1 is embedded in a living body so that the convexly curved outer surface 101b faces the skin side and the flat outer surface 102b faces the subcutaneous tissue side, the connective tissue body formation structure 1 is embedded along the internal shape of the living body, and the adhesion between the connective tissue body formation structure 1 and the inside of the living body is improved. Therefore, gaps are unlikely to occur between the convex curved outer surface 101b and the skin, or between the flat outer surface 102b and the subcutaneous tissue, and even if gaps do occur, the gaps can be narrowed. In such an embedded connective tissue body formation structure 1, connective tissue in the living body can easily enter the connective tissue body formation space 30 from the communication part 40 of the connective tissue body formation structure 1, so the time required for connective tissue body formation can be shortened. As a result, a connective tissue body with excellent quality can be more stably formed.

[0042] FIG. 12 is a perspective view showing another example of the plate member 10 constituting the connective tissue formation structure 1. As shown in FIG. 12, among the multiple plate members 10 constituting the plate member group 100, the corner portion 11 having the inclined surface 12 in one plate member 101 arranged on the outermost side is preferably provided with a convex outer inclined surface 14 connecting the inclined surface 12 and the outer surface 101b between the inclined surface 12 and the outer surface 101b of the plate member 101. The outer inclined surface 14 is a chamfered surface connecting the inclined surface 12 and the outer surface 101b at an angle of 90 degrees or more. The convex curved surface of the outer inclined surface 14 is raised in the same manner as the convex curved surface of the outer surface 101b shown in FIG. 11. When the one plate member 101 arranged on the outermost side is provided with the outer inclined surface 14 in this way, the catch of the connective tissue formation structure 1 and damage to the subcutaneous tissue during implantation are further suppressed.

[0043] Fig. 13 is a perspective view showing another example of the plate member 10 constituting the connective tissue formation structure 1. As shown in Fig. 13, it is preferable that a covering portion 60 made of a material softer than the plate member 10 is provided on at least the inclined surface 12 of the plate member 10. When the plate member 10 is provided with the covering portion 60 in this manner, even if the corner portion 11 including the inclined surface 12 gets caught on a living body, damage to the living body is suppressed, and damage to subcutaneous tissue and the like during implantation is further suppressed.

[0044] 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 1 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 30 of the connective tissue body formation structure 1 embedded in the living body, and a step (S-3) of removing the connective tissue body formation structure 1 containing the connective tissue body formed in the connective tissue body formation space 30 from the living body.

[0045] In step (S-1), the connective tissue body formation structure 1 is inserted in a predetermined site in a living body other than a human, and the connective tissue body formation structure 1 is embedded in the living body. The sheet-like connective tissue body formation structure 1 is embedded in subcutaneous tissue of the limbs, shoulders, back, abdomen, etc. As an example, a part of the skin such as the epidermis and dermis that cover the subcutaneous tissue from the outside is peeled off from the living body, the connective tissue body formation structure 1 is inserted in a plug-in manner into the subcutaneous tissue, and the partially peeled skin is sutured to the living body, thereby embedding the connective tissue body formation structure 1 in the subcutaneous tissue. When inserting the sheet-like connective tissue body formation structure 1, the connective tissue body formation structure 1 can be inserted while cutting open the subcutaneous tissue.

[0046] In step (S-2) performed after step (S-1), the connective tissue body formation structure 1 is embedded in a living body for a predetermined time, and a sheet-like connective tissue body is formed in the connective tissue body formation space 30 of the connective tissue body formation structure 1. During the embedding of the connective tissue body formation structure 1, connective tissue in the living body enters the connective tissue body formation space 30 from the communication part 40 of the connective tissue body formation structure 1, and the connective tissue in the connective tissue body formation space 30 grows, thereby forming a connective tissue body in the connective tissue body formation space 30. When the connective tissue body formation structure 1 is embedded in a living body for 8 weeks or more, a good connective tissue body is formed in the connective tissue body formation space 30. The connective tissue body is composed of fibroblasts and an extracellular matrix such as collagen.

[0047] In step (S-3) carried out after step (S-2), the connective tissue body formation structure 1 containing the connective tissue formed in the connective tissue body formation space 30 is removed from the living body. When the connective tissue formed in the connective tissue body formation space 30 is bonded to biological tissue present around the connective tissue body formation structure 1, the surrounding biological tissue and the connective tissue body formation structure 1 are cut, and the connective tissue body formation structure 1 is removed from the living body.

[0048] Furthermore, the method for forming a connective tissue body of the embodiment further includes a step (SA) of providing an insertion part into which the above-mentioned connective tissue body formation structure 1 can be inserted in a living body other than a human prior to the step (S-1), and in the step (S-1), it is preferable to insert and implant the connective tissue body formation structure 1 through the insertion part. The insertion part provided in the step (SA) can be easily formed by making a small incision in the living body, compared to conventional cylindrical connective tissue body formation substrates. Furthermore, the sheet-like connective tissue body formation structure 1 can be inserted by slightly cutting the insertion part, without repeatedly cutting the living body. This reduces the burden on the animal and makes the work easier.

[0049] Furthermore, the method for forming a connective tissue body according to the embodiment may further include a step (SB) of separating the connective tissue body from the connective tissue body formation space 30 of the connective tissue body formation structure 1 taken out from the living body after the step (S-3). In the step (SB) performed after the step (S-3), the connective tissue body is separated from the connective tissue body formation space 30 of the connective tissue body formation structure 1 taken out from the living body to obtain a sheet-like connective tissue body. When the connective tissue is formed on the outer surface of the connective tissue body formation structure 1, the connective tissue is removed from the outer surface of the connective tissue body formation structure 1 and then separated from the connective tissue body formation space 30. A connective tissue body having a desired shape can be obtained by appropriately adjusting the interval between the multiple plate members 10 and the shape of the inner surface 10a of the plate member 10.

[0050] Furthermore, when the obtained connective tissue is used for xenotransplantation to 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. Examples of decellularization include methods of eluting and washing the extracellular matrix by ultrasonic treatment, surfactant treatment, and enzyme treatment such as collagenase. Examples of dehydration include washing with a water-soluble organic solvent such as methanol, ethanol, and isopropyl alcohol. Examples of fixation include treatment with an aldehyde compound such as glutaraldehyde and formaldehyde.

[0051] According to the embodiment described above, by arranging a plurality of plate members 10 each having an inclined surface 12 at at least one corner 11 facing each other in parallel and spaced apart, and optimizing the shape and arrangement of the plurality of plate members 10 constituting the connective tissue formation structure 1, the connective tissue formation structure 1 can be suitably implanted in a living body larger than a human. Furthermore, the connective tissue formation structure 1 is excellent in at least one of insertion into the living body, stability after implantation in the living body, and productivity of the connective tissue body.

[0052] In the above, an example of the inclined surface 12 composed of two flat surfaces 12a and 12b as shown in Figures 3 and 4 is shown, but the inclined surface may be composed of three or more flat surfaces. When the inclined surface is composed of three or more flat surfaces, it becomes easier to insert and the stability after implantation is further improved.

[0053] Although the above describes an example of a planar inclined surface 12, the inclined surface 12 may be curved. As shown in Fig. 14, the inclined surface 12 is curved, and in a cross section of the plate member 10 parallel to the in-plane direction L of the plate member 10, the inclined surface 12 is arc-shaped. The connective tissue formation structure 1 having the curved inclined surface 12 is easier to insert, and the stability after implantation is further improved. The inclined surface 12 may be a shape in which a curved surface and a flat surface are mixed.

[0054] 15, all of the inclined surfaces 12 provided at the adjacent corners 11 are connected to each other and are curved, and the inclined surfaces 12 may be arc-shaped in a cross section of the plate member 10 parallel to the in-plane direction L of the plate member 10. Such a connective tissue formation structure 1 can be further easily inserted and removed, and its stability after implantation is further improved.

[0055] 12 shows an example in which the outer inclined surface 14 is provided on one plate member 101 arranged on the outermost side, but the outer inclined surface may be provided on the other plate member 102 arranged on the outermost side in addition to the one plate member 101. The outer inclined surface provided on the plate member 102 connects the inclined surface 12 and the outer surface 102b at an angle of equal to or greater than a right angle between the inclined surface 12 and the outer surface 102b.

[0056] In addition, in the above, an example was shown in which the connective tissue body formation structure 1 includes three plate members 10, but the connective tissue body formation structure 1 may include two plate members 10 as shown in Fig. 16, or may include four or more plate members. The number of plate members 10 is appropriately changed depending on the number of connective tissue bodies to be formed.

[0057] Further, although an example in which spacing members 20 are provided in the vicinity of all corners 11 of plate member 10 has been described above, the locations and number of spacing members are not particularly limited, and for example, as shown in Fig. 17, one spacing member 20 may be provided in the center of plate member 10. Further, the shape of spacing member 20 is not particularly limited, and may be a rectangular column shape.

[0058] The plate member 10 may have one or more through holes penetrating from one main surface to the other main surface. The through holes realize communication between the connective tissue body formation space 30 and the outside of the connective tissue body formation structure 1, or communication between adjacent connective tissue body formation spaces 30. Since the connective tissue enters the connective tissue body formation space 30 from the outside of the connective tissue body formation structure 1 through the communication part 40 and the through holes, a good sheet-like connective tissue body can be easily formed in the connective tissue body formation space 30. Furthermore, since the connective tissue enters multiple adjacent connective tissue body formation spaces 30 through the through holes, a good connective tissue body can be easily formed in multiple connective tissue body formation spaces 30.

[0059] 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 scope of the claims of the present disclosure, and can be modified in various ways within the scope of the present disclosure. [Explanation of symbols]

[0060] 1 Structure for connective tissue formation 10 Plate members 10a Inner surface of plate member 100 Plate members group 101 One of the outermost plate members 102 The other outermost plate member 101b, 102b Outer surface of plate member 11 Corner 12 Slope 12a 1st plane part 12b 2nd plane part 13 Side 13a 1st side 13b Second side 13c 3rd aspect 13d 4th side 14 Outer slope 20 Spacer 30 Connective tissue formation space 40 Communication part 50 Connective tissue formation promoter 60 Covering part L In-plane direction of plate member

Claims

1. A plate member group including a plurality of rectangular plate members facing each other and spaced apart from each other; At least one spacing member provided between the plurality of plate members constituting the plate member group and spacing the plurality of plate members apart from each other; A structure for forming a connective tissue body, comprising: At least one corner of each of the plate members is provided with an inclined surface between two adjacent side surfaces of each of the plate members, the inclined surface being connected to the two adjacent side surfaces; The plurality of plate members are parallel to each other and spaced apart from each other, Between the plurality of plate members, a connective tissue body formation space extending in an in-plane direction of the plurality of plate members and capable of forming a connective tissue body, and at least one communication part communicating the connective tissue body formation space with the outside of the connective tissue body formation structure are provided, For use by implantation in non-human organisms A structure for forming a connective tissue body, comprising:

2. The connective tissue formation structure according to claim 1, wherein in a cross section of the plate member parallel to an in-plane direction of the plate member, the angle between the inclined surface and each of the side surfaces connected to the inclined surface is greater than 90 degrees and less than 180 degrees.

3. The connective tissue formation structure according to claim 2 , wherein the inclined surface is flat.

4. The connective tissue formation structure according to claim 2 , wherein the inclined surface is curved, and in a cross section of the plate member parallel to an in-plane direction of the plate member, the inclined surface is arc-shaped.

5. The connective tissue formation structure according to any one of claims 1 to 4, wherein the inclined surfaces are provided at a plurality of adjacent corners of each of the plate members.

6. The connective tissue formation structure according to any one of claims 1 to 5, wherein the inclined surfaces are provided at all corners of each of the plate members.

7. 7. The connective tissue formation structure according to claim 5, wherein the inclined surfaces provided at the adjacent corners are connected to each other.

8. The connective tissue formation structure according to any one of claims 1 to 7, wherein a connective tissue formation promoting substance that promotes the formation of connective tissue is provided on one of the two opposing inner surfaces of the plurality of plate members.

9. The connective tissue formation structure according to any one of claims 1 to 8, wherein, among the plurality of plate members constituting the plate member group, the outer surface of one plate member arranged on the outermost side is convexly curved, and the outer surface of the other plate member arranged on the outermost side is flat.

10. The connective tissue formation structure according to any one of claims 1 to 9, wherein a corner portion having the inclined surface in one of the plate members arranged on the outermost side among the plurality of plate members constituting the plate member group is provided with a convex curved outer inclined surface connecting the inclined surface and the outer surface between the inclined surface and the outer surface of the plate member.

11. The connective tissue formation structure according to any one of claims 1 to 10, wherein a covering portion made of a material softer than the plate member is provided on at least the inclined surface of the plate member.

12. A step (S-1) of inserting and implanting the connective tissue formation structure 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 implanted in the living body; a step (S-3) of removing the connective tissue formation structure containing the connective tissue formed in the connective tissue formation space from the living body; A method for forming a connective tissue structure, comprising the steps of:

13. The method further includes a step (SA) of providing an insertion part into a living body other than a human, into which the connective tissue body formation structure can be inserted, prior to the step (S-1), The method for forming a connective tissue body according to claim 12, wherein in the step (S-1), the connective tissue body formation structure is inserted through the insertion portion and embedded.

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