Tissue reinforcing material

Abstract

[Problem] To improve the pressure resistance of a tissue reinforcing material. [Solution] A tissue reinforcing material has a sheet-like body 10 that includes fibers composed of biodegradable material. The body 10 has formed therein a plurality of through-holes 11 and comprises a fused part 40 which is formed from fibers gathered and fused around the through-holes. The volume density of the body is 0.15 g / cm3 or less, and the porosity of a portion of the body excluding the through-holes is 50% or more.

Description

Tissue reinforcement material

[0001] This invention relates to a tissue reinforcing material.

[0002] In the medical field, surgical procedures to join living organs together (for example, gastrointestinal anastomosis) are well known. When such procedures are performed, it is known that the absence of delays in fusion at the junction where living organs are joined is an important determinant of postoperative prognosis.

[0003] Various methods and medical instruments are used in the procedure of anastomosing living organs. For example, methods using biodegradable sutures to suture living organs and methods using mechanical anastomosis devices that perform anastomosis with staples have been proposed. In particular, when performing anastomosis using a mechanical anastomosis device, the bonding strength between living organs at the junction can be increased compared to methods using sutures, thereby reducing the risk of anastomotic leakage.

[0004] Special Publication No. 2008-516678

[0005] In the anastomosis device described in Patent Document 1, a sheet-like member such as a support structure (hereinafter referred to as a tissue reinforcement material) is inserted to prevent leakage or rupture at the anastomosis site, thereby promoting the healing of the anastomosis site. Such tissue reinforcement materials are usually relatively thin and soft. The present inventors are diligently studying how to improve the pressure resistance of tissue reinforcement materials when in use.

[0006] Therefore, the present invention aims to improve the pressure resistance of tissue reinforcing materials.

[0007] The present invention is achieved by any one of the following means (1) to (12).

[0008] (1) The main body has a sheet-like thickness containing fibers made of biodegradable material, the main body has a plurality of through holes formed therein, and the fibers are gathered and fused together around the through holes, the volume density of the main body is 0.15 g / cm³ ３ A tissue reinforcing material, wherein the void ratio of the portion of the main body excluding the through-hole is 50% or more.

[0009] (2) A tissue reinforcing material having a sheet-like main body containing fibers made of biodegradable material, wherein when the equivalent circle diameter calculated from the area of ​​the voids where the fibers are not present is measured in a plan view along the thickness direction of the main body, the size distribution ratio of the equivalent circle diameter of the voids is such that the total area of ​​the voids with an equivalent circle diameter of less than 400 μm is 1.0% or more and 25% or less of the total area of ​​the main body, and furthermore, the total area of ​​the voids with an equivalent circle diameter of 400 μm or more and 1000 μm or less is 3.3% or more and 43% or less of the total area of ​​the main body, as described in (1) above.

[0010] (3) The tissue reinforcing material according to (1) above, wherein the distribution ratio of the equivalent circle diameter is such that the total area of ​​the voids with a pore diameter of less than 400 μm is 2.2% or more and 20% or less of the total area of ​​the main body, and furthermore, the total area of ​​the voids with a pore diameter of 400 μm or more and 1000 μm is 10% or more and 32% or less of the total area of ​​the main body.

[0011] (4) The mass per unit area of ​​the main body is 17 g / m² ２ 120g / m or more ２ The following is a tissue reinforcing material as described in any of (1) to (3) above.

[0012] (5) The mass per unit area of ​​the main body is 44 g / m² ２ Upper 120g / m ２ The following are tissue reinforcing materials as described in any of (1) to (3) above.

[0013] (6) The tissue reinforcing material according to any one of (1) to (5) above, wherein the ratio of the total area of ​​the void portion to the total area of ​​the main body portion including the void portion is 15% or more and 69% or less.

[0014] (7) The tissue reinforcing material according to any one of (1) to (5) above, wherein the ratio of the total area of ​​the voids to the total area of ​​the main body including the voids is 15% or more and 29% or less.

[0015] (8) The tissue reinforcing material according to any one of (1) to (7) above, wherein the thickness of the main body is 0.15 mm or more and 0.57 mm or less.

[0016] (9) The main body portion is used by being sandwiched between the anastomoses of a living organ, as described in any of (1) to (8) above.

[0017] (10) The tissue reinforcing material according to any one of (1) to (9) above, wherein the fused portion comprises a portion in which the fibers are completely fused and a portion in which the area around the fibers is fused while maintaining the shape of the fibers.

[0018] (11) The tissue reinforcing material according to any one of (1) to (10) above, wherein the main body portion comprises a proximity portion located near the through hole in the planar direction of the main body portion and a distal portion located further away from the through hole in the planar direction than the proximity portion, and the fibers are present at a higher density in the proximity portion than in the distal portion.

[0019] (12) The tissue reinforcing material described in (11) above, wherein the fused portion is formed in the vicinity thereof.

[0020] According to the tissue reinforcing materials described in (1) to (12) above, the pressure resistance of the tissue reinforcing material can be improved.

[0021] This is a perspective view showing a tissue reinforcement material according to an embodiment. This is an enlarged cross-sectional view showing the through-hole in the main body of the tissue reinforcement material. This is a diagram showing the shape pattern of the through-hole in the tissue reinforcement material. This is a diagram showing the shape pattern of a modified example of the through-hole in the tissue reinforcement material. This is a diagram showing the shape pattern of a modified example of the through-hole in the tissue reinforcement material. This is a diagram showing the shape pattern of a modified example of the through-hole in the tissue reinforcement material. This is an exploded perspective view showing a part (tip) of a medical instrument used when anastomosing a living organ using the tissue reinforcement material. This is an enlarged image showing the fused portion of the tissue reinforcement material. This is an enlarged image showing the fused portion of the tissue reinforcement material. This is an enlarged image showing the fused portion of the tissue reinforcement material. This is a flowchart showing the manufacturing method of the tissue reinforcement material according to an embodiment. This is a diagram showing a needle member used in the manufacturing method of the tissue reinforcement material according to the first embodiment. This is a schematic diagram showing the formation of a through-hole in a sheet member with the needle member. This is a diagram showing a needle member used in the manufacturing method of the tissue reinforcement material according to the second embodiment. This is a graph showing examples and comparative examples when the horizontal axis is set to an opening ratio of 0 to 400 μm and the vertical axis is set to an opening ratio of 400 μm to 1000 μm in the tissue reinforcement material according to Experiment 1. This graph shows examples and comparative examples of the tissue reinforcement material used in Experiment 2, where the horizontal axis represents the porosity of the wire diameter portion and the vertical axis represents the volume density.

[0022] <First Embodiment> Hereinafter, embodiments for carrying out the present invention will be described in detail with reference to the drawings. The embodiments shown herein are illustrative examples for the purpose of embodying the technical idea of ​​the present invention and do not limit the present invention. Furthermore, all other implementable forms, examples, and operational techniques that can be conceived by those skilled in the art without departing from the spirit of the present invention are included in the scope and spirit of the present invention, as well as in the claims and their equivalents.

[0023] Furthermore, the drawings attached to this specification may be schematically represented with changes to scale, aspect ratio, shape, etc., from the actual object for the sake of illustration and ease of understanding, but these are merely examples and do not limit the interpretation of the present invention.

[0024] Furthermore, in the following explanations, ordinal numbers such as "first" and "second" are used, but unless otherwise specified, they are used for convenience and do not prescribe any particular order.

[0025] <Tissue Reinforcement Material> Figure 1 is a perspective view showing a tissue reinforcement material 100 according to an embodiment. Figure 2 is an enlarged view showing the through-holes 11 of the tissue reinforcement material 100. The tissue reinforcement material 100 is positioned sandwiched between two or more biological organs to be anastomosed (one site to be joined and the other site to be joined), and is configured as a flat sheet with multiple through-holes 11. Here, "positioned sandwiched between two or more biological organs to be anastomosed" means at least one of the following: the tissue reinforcement material 100 is positioned in a state where it is directly or indirectly in contact with the biological organs, the tissue reinforcement material 100 is positioned with a spatial gap formed between it and the biological organs, or the tissue reinforcement material 100 is positioned in both states (for example, the tissue reinforcement material 100 is in contact with one biological organ and not in contact with the other biological organ). Examples of biological organs include the digestive tract such as the large intestine and jejunum, and tubular organs such as the pancreatic duct. The tissue reinforcement material 100 is positioned between two or more biological organs to be anastomosed (one site to be joined and the other site to be joined), thereby reinforcing the anastomotic site of the biological organs in a shape suitable for the anastomotic site until the anastomotic site of the biological organs fuses. As shown in Figure 1, the tissue reinforcement material 100 comprises a main body 10, a fixing part 20, an insertion part 30, and a fusion part 40. The tissue reinforcement material 100 may also consist of a main body 10, an insertion part 30, and a fusion part 40, without the fixing part 20. Note that some drawings show a Cartesian coordinate system, and below, the plane direction of the main body 10 will be referred to as the plane direction YZ, and the thickness direction will be referred to as the thickness direction X. Further details are provided below.

[0026] <Main body> The main body 10 is positioned between two biological organs to be anastomosed (for example, two large intestines, or a pancreatic duct and a jejunum) and is configured as a sheet that can follow the movement of the biological organs to be anastomosed. In this way, the main body 10 is used by being sandwiched between the anastomoses of the biological organs.

[0027] As shown in Figure 1, the main body 10 is formed in a circular shape as an example, and as shown in Figure 2, it has a plurality of through holes 11 formed to be inserted in the thickness direction X (axial direction) of the circular shape. As an example of the size (hole diameter D) of the through holes 11 of the main body 10, it is preferably 0.1 to 6 mm, more preferably 0.3 to 4 mm, and even more preferably 0.6 to 1.5 mm. The main body 10 can promote adhesion effect through the through holes 11. The ratio of the dimension of the through hole 11 (the distance shown in Figure 2, which is the hole diameter D of the through hole 11) to the pitch P (the distance shown in Figure 2, which is the distance between the opening edges of two through holes 11) can be configured to be 0.25 or more and less than 40. Since the main body 10 has a plurality of through holes 11, there are a plurality of values ​​for the hole diameter D corresponding to each through hole 11. Therefore, in this embodiment, when calculating the value of the ratio described above, the arithmetic mean of two or more values ​​of the hole diameter D corresponding to each of the plurality of through holes 11 is used as the representative value of the hole diameter D. On the other hand, the pitch P of the multiple through holes 11 is defined by the shortest distance between the openings of two through holes 11. However, there are multiple values ​​for pitch P corresponding to combinations of adjacent through holes 11. Therefore, in this embodiment, when calculating the ratio value described above, the arithmetic mean of two or more pitch P values ​​corresponding to each combination of adjacent through holes 11 is used as the representative value of pitch P. However, the pitch P described above is an example and may be periodic or random. Note that the (true) circle described as the shape of the main body 10 is an example and may also be configured to include other shapes such as ellipses, polygons such as quadrilaterals, and star shapes.

[0028] Figure 3 shows the shape pattern of the through-hole 11 in the main body 10, and Figures 4 to 6 show the shape patterns of modified examples of the through-hole 11 in the main body 10. In Figures 2 and 3, the through-hole 11 is shown with the same shape and equal pitch. However, the shape pattern of the through-hole 11 is not limited to this. In addition to the above, through-holes 11 of different sizes may be arranged at equal intervals as shown in Figure 4, through-holes of the same size may be arranged at a 60° staggered pitch (staggered arrangement) as shown in Figure 5, or through-holes 11 of different sizes may be arranged randomly as shown in Figure 6.

[0029] The thickness of the main body portion 10 (dimension T shown in FIG. 2) is not particularly limited, but is preferably 0.05 to 0.7 mm, more preferably 0.25 to 0.45 mm. Note that the above-described numerical values for the size such as the above-described thickness and size are also examples, and sizes other than the above may be used. When the dimension T, which is the thickness of the main body portion 10, is 0.7 mm or less (particularly when it is 0.45 mm or less), the flexibility of the main body portion 10 can be enhanced. Thereby, the main body portion 10 adheres to the living body organ, and the followability with respect to the movement of the living body organ is enhanced. On the other hand, when the dimension T, which is the thickness of the main body portion 10, is 0.05 mm or less, the strength of the main body portion 10 is insufficient, and it becomes difficult to arrange the tissue reinforcing material 100 between the living body organs to be anastomosed while being sagged.

[0030] When measuring the equivalent circle diameter calculated from the area of the void portion (including the through hole 11) in which no fiber exists in a plan view along the thickness direction X of the main body portion 10, the size distribution rate of the equivalent circle diameter of the void portion (hereinafter referred to as the pore size distribution rate) is such that the total area of the void portion having an equivalent circle diameter of less than 400 μm is 1.0% or more and 25% or less, more preferably 2.2% or more and 20% or less, with respect to the total area of the main body portion 10. Further, the total area of the void portion having an equivalent circle diameter of 400 μm or more and 1000 μm or less is 3.6% or more and 41% or less, more preferably 10% or more and 30% or less, with respect to the total area of the main body portion 10. The mass per unit area of the main body portion 10 (hereinafter referred to as the surface density) is 17 g / m ２ or more and 120 g / m ２ or less, more preferably 44 g / m ２ or more and 120 g / m ２ or less. Further, the ratio (hereinafter referred to as the porosity) of the total area of the void portion to the entire area of the main body portion 10 including the void portion is 15% or more and 69% or less, more preferably 15% or more and 29% or less. Also, the thickness of the main body portion 10 can be configured to be 0.15 mm or more and 0.57 mm or less. The volume density of the main body portion 10 is 0.15 g / cm ３ or less, and the porosity of the portion of the main body portion 10 excluding the through hole can be configured to be 50% or more.

[0031] The main body 10 can be made from a sheet-like molded product formed by knitting or weaving a multifilament of multiple fibers (e.g., yarn) made of biodegradable material. In other words, the main body 10 can be made from a biodegradable sheet made of biodegradable fibers. There are no particular restrictions on the constituent materials of the main body 10; for example, biodegradable resins that induce biological reactions can be used.

[0032] Examples of biodegradable resins include (1) polymers selected from the group consisting of aliphatic polyesters, polyesters, polyacid anhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphate esters, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose; and (2) copolymers composed of one or more monomers that make up (1) above.

[0033] In other words, the biodegradable sheet preferably contains at least one biodegradable resin selected from the group consisting of polymers selected from the group consisting of aliphatic polyester, polyester, polyacid anhydride, polyorthoester, polycarbonate, polyphosphazene, polyphosphate ester, polyvinyl alcohol, polypeptide, polysaccharide, protein, and cellulose, and copolymers composed of one or more monomers constituting the polymer. The main body 10 is preferably made of a bioabsorbable material such as polyglycolic acid (PGA) or PLGA (polylactic acid / glycolic acid copolymer).

[0034] In this embodiment, the main body 10 is made of a yarn (multifilament) composed of a plurality of fibers spun from PGA polymer. This multifilament is processed by a knitting machine for flat knitting (weft knitting) to form a sheet, and further, while heating a plurality of these sheets stacked, the forming process of the through holes 11 is performed, whereby the main body 10 with higher rigidity than before heating is created. The main body 10 thus created causes a biological reaction by a constituent material such as a biodegradable resin that constitutes the main body 10. The main body 10 induces the expression of biological components such as fibrin by this action. The biological components induced in this way can promote healing by accumulating so as to penetrate the through holes 11 of the main body 10 from both sides in the surface direction YZ. Therefore, by placing the main body 10 of the tissue reinforcing material 100 in a sandwiched state between the biological organs to be joined (for example, between the intestinal tubes that anastomose in the large intestine, between the cut surfaces of the intestinal tubes that anastomose in the large intestine, between the pancreatic parenchyma and the jejunum), the healing is promoted by the above mechanism. Further, the main body 10 can be formed by warp knitting (warp knitting) or a non-woven fabric and subjected to needle punching processing.

[0035] FIG. 7 is an exploded perspective view showing the tip of a medical instrument 200 used when placing the tissue reinforcing material 100 on a biological organ. The medical instrument 200 includes a first instrument 210 and a second instrument 250. The medical instrument 200 is also called a circular stapler, the first instrument 210 can also be called a trocar, and the second instrument 250 can also be called an anvil. A part on the outer side of the main body 10 is deformed by being sandwiched between a staple discharged from a discharge part 240 (corresponding to a staple part) of the first instrument 210 of the medical instrument 200 and a contact part 270 of the second instrument 250 facing the discharge part 240, and is integrated into a first joined part and a second joined part. A punching part 230 (corresponding to a cutter part) is provided in a circumferential shape inward in the radial direction of the discharge part 240, and biological tissue and the tissue reinforcing material 100 can be punched out in a circumferential shape. A positioning part 220 provided at the center of the first instrument 210 is housed inside a hollow shaft 260 provided so as to protrude from a contact part 270 that contacts the discharge part 240 in the second instrument 250, and the first instrument 210 and the second instrument 250 are aligned.

[0036] <Fixing portion> The fixing portion 20 is provided to prevent or suppress the displacement of the tissue reinforcing material 100 and prevent its detachment when the tissue reinforcing material 100 is placed between the first joint site and the second joint site. As shown in FIG. 1, the fixing portion 20 is formed along the inner peripheral edge in the hollow circular shape of the main body portion 10. That is, the fixing portion 20 is formed so as to surround the central portion Pt (virtual point) of the tissue reinforcing material 100 in the plane direction YZ. The tissue reinforcing material 100 is arranged in the order of the fixing portion 20 and the main body portion 10 in sequence from the central portion Pt to the outer direction in the plane direction YZ.

[0037] The fixing portion 20 is configured in a shape without providing the through hole 11 in the main body portion 10. The fixing portion 20 can be formed of a bioabsorbable material such as a thermoplastic resin such as PGA (polyglycolic acid), PLA (polylactic acid), PLGA (polylactic acid-glycolic acid copolymer), PDS (polydioxanone), PCL (polycaprolactone).

[0038] The fixing portion 20 may be provided over the entire circumference on the inner side in the plane direction YZ of the main body portion 10, or may be provided at one or a plurality of locations partially within the entire circumference. Also, although the fixing portion 20 is configured coaxially with the inner edge portion, the central position may be displaced from the main body portion 10 as long as it does not enter the fusion region. The inner side of the fixing portion 20 and the main body portion 10 is punched out by the punching portion 230 of the first instrument 210 of the medical instrument 200 during the procedure and separated from the outer side of the main body portion 10. Note that the fixing portion 20 may not be provided. When the fixing portion 20 is not provided, the inner peripheral edge of the tissue reinforcing material 100 is constituted by the main body portion 10 provided with the through hole 11 continuous inward from the main body portion 10.

[0039] In the present embodiment, the fixing portion 20 is arranged at a predetermined position by heat fusion to the main body portion 10 after the process of creating the through hole 11 involving heating. Note that the method of arranging the fixing portion 20 with respect to the main body portion 10 is not limited to only heat fusion, and a biocompatible adhesive or the like may be used.

[0040] <Insertion Section> As shown in Figure 1, the insertion section 30 is spaced apart from the outer peripheral edge of the main body 10 in the surface direction YZ of the main body 10 and is located approximately in the center in the surface direction, and in this embodiment it is formed by the fixing section 20. The insertion section 30 is configured to be insertable onto the shaft 260 of the second instrument 250 of the medical instrument 200. In this embodiment, the insertion section 30 has a hole diameter larger than the hole diameter D of each through hole 11, so it is configured to be insertable onto the shaft 260. The shaft 260 of the second instrument 250 is configured to accommodate the positioning section 220 of the first instrument 210.

[0041] In this embodiment, the insertion portion 30 is configured to be approximately circular when viewed from the thickness direction X. However, the specific shape of the hole is not limited to a circular shape as long as the main body portion 10 can promote the fusion of biological tissue. The cross-section of the insertion portion 30 is preferably a perfect circle, but it may also be configured to be linear, elliptical, triangular, square, concave, convex, cross-shaped, or other types of notches.

[0042] In this embodiment, the insertion portion 30 is created by cutting out a substantially circular section at a predetermined position of the main body portion 10 after the through-hole 11 has been created through a heating process. However, the method of creating the insertion portion 30 is not limited to cutting; for example, it may be cut out after heat processing.

[0043] <Fused portion> Figures 8 to 10 are images showing a part of the fused portion 40. The fused portion 40 is configured as a part where fibers gather and fuse together around the through hole 11. The through hole 11 of the main body portion 10 is formed along the thickness direction X of the main body portion 10. The fused portion 40 is configured to be formed along the thickness direction X.

[0044] The fused portion 40 shown in Figure 9 comprises a first portion 41 in which the fibers are completely fused, as shown in Figure 8, and a second portion 42 in which the area around the fibers is fused while maintaining the shape of the fibers. Here, "completely fused" means that the fibers are a single, unified entity (so integrated that even when examined under a microscope, the originally separate fibers cannot be distinguished). "The area around the fibers is fused while maintaining the shape of the fibers" means that the fibers are not a single, unified entity (so integrated that even when examined under a microscope, the originally separate fibers cannot be distinguished), but there is a portion in which the area around the fibers is melted and the fibers are fused together (so integrated that even when examined under a microscope, the originally separate fibers can be distinguished).

[0045] As shown in Figure 10, the main body 10 comprises a proximity portion 12 located near the through hole 11 in relation to the fusion portion 40, and a distal portion 13 located further away from the through hole 11 in the plane direction YZ than the proximity portion 12. The proximity portion 12 includes the opening edge of the through hole 11. The distal portion 13 includes the area around the center of the distance (pitch P) between two through holes 11. Here, in the main body 10, the area from the edge of one through hole 11 to less than 50% of the length between adjacent through holes 11 can be the proximity portion 12, and the remaining area can be the distal portion 13. The proximity portion 12 is configured to have a higher fiber density than the distal portion 13.

[0046] The fused portion 40 is formed in the vicinity portion 12 and distal portion 13 on one side (first surface) in the thickness direction X, as described later, and is formed only in the vicinity portion 12 on the other side (second surface opposite to the first surface). The fused portion 40 can be formed so that at least a portion of the multifilaments, which are made up of multiple fibers, are fused together. However, the fused portion 40 may be formed so that at least a portion of the fibers (threads) of the multifilament are fused together. The size of the fused portion 40 is not particularly limited, but for example, it can be set to 0.015 mm to 0.7 mm. The ratio of the fused portion 40 to the unfused portion can be set to 3% or more and 100% or less. Also, the occupancy rate of the fused portion 40 relative to the main body portion 10 when the main body portion 10 is viewed in plan (viewed from the thickness direction X) can be set to 0.002% or more.

[0047] <Method for forming fused portions> Next, a method for forming the fused portions 40 within the tissue reinforcing material 100 will be described. Figure 11 is a flowchart showing the method for forming the tissue reinforcing material 100 according to an embodiment. Figure 12 shows a needle member 320 used in the method for forming the fused portions 40 according to the first embodiment. Figure 13 shows the process of forming through holes 11 in the sheet member S used when forming the fused portions 40 in the tissue reinforcing material 100. The sheet member S is a sheet-like member made of a woven fabric containing fibers made of biodegradable material, without the through holes 11 formed therein.

[0048] One example of a method for forming the fused portion 40 is to use a forming member 300, as shown in Figure 12, in which a base portion 310 having a circular plane that serves as a base is provided with numerous heat-conductive needle members 320 at its tip. The base portion 310 of the forming member 300 incorporates a component that can be heated by generating ultrasonic waves, etc., and by generating heat in the base portion 310, heat can be conducted to the multiple needle members 320. In this embodiment, the forming member 300 is preheated. The needle members 320 are heated to a temperature above the melting temperature of the fibers made of the biodegradable material forming the main body portion 10, or above the melting point of the fibers (around 200°C, around 218°C, or 218°C or above for PGA, or around 200°C, around 215°C, or 215°C or above for PLGA). Then, the needle members 320 are inserted into the sheet member S of the tissue reinforcement material 100 before processing (S1), the base portion 310 is brought into contact with the sheet member S, and pressing is performed.

[0049] As a result, as shown in Figure 13, the area around the edge of the through hole 11 drilled by the needle member 320 (corresponding to the vicinity 12 of the main body 10) in the sheet member S is heated and melted, and the fibers around the through hole 11 melt together to form a fused portion 40 (S2). In this embodiment, the needle member 320 has a shape in which a cylindrical portion and a conical portion of the same diameter are superimposed on the base portion 310, but the shape of the needle member 320 is not particularly limited as long as a through hole 11 with the desired hole diameter D can be formed. For example, the needle member 320 may be conical, pyramidal, cylindrical, tapered, etc. Also, the needle member 320 may have the same or equivalent diameter as the hole diameter D. In this embodiment, the diameter of the cylindrical portion and the diameter of the bottom surface of the conical portion of the needle member 320 have the same diameter as the hole diameter D, and the cylindrical portion penetrates and drills through the sheet member S. However, if a through hole 11 can be formed with the desired hole diameter D, the cylindrical portion does not need to penetrate the sheet member S.

[0050] In Figure 13, part 14 indicates the area of ​​the sheet member S that the needle member 320 directly contacts, and part 15 indicates the area (first surface) that the base 310 directly contacts. The areas 14 and 15 where the base 310 and the needle member 320 directly contact each other experience a greater heat load than the areas where the base 310 and the needle member 320 do not directly contact each other (second surface). Therefore, when viewed from the thickness direction X, one side of the sheet member S (front side, areas 14 and 15 where the base 310 and the needle member 320 directly contact each other, the first surface) has more melted fibers and higher rigidity compared to the other side (back side, area where the base 310 and the needle member 320 do not directly contact each other, the second surface).

[0051] Furthermore, as shown in Figure 13, the surface (part 15) of the sheet member S that contacts the base 310 is an uneven plane due to the fibers, so there are parts that do not directly contact the base 310. The through hole 11 is formed by avoiding the fibers of the sheet member S at the edge (corresponding to the vicinity 12 of the main body 10) that is perforated by the needle member 320. As a result, the fiber density in the vicinity 12 of the through hole 11 is higher than in the distal part 13. In other words, the density of the through hole 11 is higher than the density of the surface of the sheet member S. The part 15, which is heated by contact with the base 310 and in which the fibers are partially melted and fused, is formed only on one side of the main body 10, so that the main body 10 can have both a certain degree of flexibility and rigidity. Furthermore, on one side (front side, the parts 14, 15, first surface) when viewed from the thickness direction X where the base 310 is in direct contact, the fused portion 40 is formed in the near portion 12 and the distal portion 13. On the other side (back side, the part where the base 310 and the needle member 320 are not in direct contact, second surface), the fused portion 40 is formed only in the near portion 12. The portion away from the vicinity of the needle member 320 (corresponding to the distal portion 13 of the main body 10) does not melt completely due to heat, but the fused portion 40 is formed in a state where it melts slightly due to heat conduction and the fibers do not completely melt. The fused portion 40 may be formed by fusing the threads between the multifilaments, or by fusing bundled multifilaments together. However, fusing bundled multifilaments together is expected to increase rigidity.

[0052] The number of sheet members S used to form the main body 10 is not particularly limited; it may be one sheet or two or more sheets, but preferably two to eight sheets, and even more preferably four sheets because they provide a good balance between heating conditions and strength. By forming the through holes 11 while applying heat, the area around the edges is melted, making it easier to maintain the shape of the through holes 11.

[0053] After heat is applied to the needle member 320, the sheet member S is cooled (S3), and the needle member 320 is removed from the sheet member S (S4). The cooling method is not particularly limited and may be performed by natural cooling or forced cooling using air, etc. Cooling may be performed with the needle member 320 still inserted, or after removing the needle member 320 from the sheet member S. When the heated needle member 320 is used to puncture and process the sheet member S as described above, and the needle member 320 is separated from the sheet member S and cooled, protrusions may form around the edges. These protrusions make positioning easier. Furthermore, the hardness of the sheet member S and the size and distribution of the through-holes can be adjusted by changing the temperature, time, pressure of the heat press, the diameter and pitch of the needle member, etc.

[0054] As described above, the tissue reinforcement material 100 according to this embodiment has a sheet-like main body portion 10 containing fibers made of biodegradable material. The main body portion 10 has a plurality of through holes 11 formed therein, and a fused portion 40 in which fibers gather and fuse around the through holes 11. By configuring it in this way, the overall rigidity of the tissue reinforcement material 100 is increased, and the occurrence of twisting or shifting during use can be prevented or suppressed. In addition, by increasing the rigidity of the main body portion 10, fraying when the tissue reinforcement material 100 is punched out with a stapler such as a medical instrument 200 can be prevented or suppressed, and it can be punched out more easily. The volume density of the main body portion 10 is 0.15 g / cm³. ３ The void ratio in the portion of the main body 10 excluding the through-holes 11 is set to 50% or more. By configuring it in this way, there are many three-dimensional voids in the portion where the mesh fibers are densely packed (hereinafter referred to as the wire diameter portion), making it easier for biological components such as fibrin and cells to adhere and proliferate when they invade. In other words, it is easier for the tissue reinforcement material 100 to function as a scaffold, and thus the pressure resistance of the tissue reinforcement material 100 can be improved.

[0055] Furthermore, when measuring the equivalent circle diameter calculated from the area of ​​the voids where no fibers exist in a plan view along the thickness direction X of the main body 10, the distribution of the equivalent circle diameter size of the voids is such that the area of ​​voids less than 400 μm is 1.0% to 25%, more preferably 2.2% to 20%, of the total area of ​​the main body, and the total area of ​​voids between 400 μm and 1000 μm is 3.6% to 41%, more preferably 10% to 30%, of the total area of ​​the main body. By configuring it in this way, when biological components such as fibrin and cells invade voids less than 400 μm, they can easily adhere and proliferate, making it easier for the tissue reinforcement material 100 to function as a scaffold, and it is expected that the adhesion effect between tissues in voids between 400 μm and 1000 μm will be improved.

[0056] Furthermore, the mass per unit area of ​​the main body 10 is 17 g / m². ２ 120g / m or more ２ More preferably, 44 g / m ２ 120g / m or more ２ The following is the configuration. By configuring it in this way, the adhesion effect can be improved.

[0057] Furthermore, the ratio of the total area of ​​the void portion to the total area of ​​the main body portion 10 including the void portion is 15% to 69%, more preferably 15% to 29%. By configuring it in this way, the adhesion effect can be improved.

[0058] Furthermore, by making the thickness of the main body 10 between 0.15 mm and 0.57 mm, the adhesion effect can be more easily achieved.

[0059] Furthermore, the main body 10 is configured to be used by being sandwiched between the anastomoses of living organs. This configuration promotes the fusion of separated living organs and contributes to the anastomosis of the relevant sites.

[0060] Furthermore, the fused portion 40 comprises a first portion 41 in which the fibers are completely fused and a second portion 42 in which the periphery of the fibers is fused while maintaining the shape of the fibers. In this way, the presence of the first portion 41 as well as the second portion 42 in the fused portion 40 makes it easier for biological components to penetrate the gaps between the fibers, thereby making it easier to exert an adhesion effect.

[0061] Furthermore, the main body portion 10 comprises a proximity portion 12 located near the through hole 11 in the YZ plane direction of the main body portion 10, and a distal portion 13 located further away from the through hole 11 in the YZ plane direction than the proximity portion 12. The proximity portion 12 is configured to have a higher fiber density than the distal portion 13. This configuration makes it easier to improve the strength of the main body portion 10, thereby making it easier to maintain the shape of the through hole 11.

[0062] Furthermore, the fused portion 40 is formed in the vicinity portion 12 and the distal portion 13 of the portion 15 (first surface) that is in direct contact with the base portion 310 and the needle member 320 in the thickness direction X of the main body portion 10. The fused portion 40 is formed only in the vicinity portion 12 on the side opposite to portion 15 (second surface) in the thickness direction X. This configuration makes it easier to maintain the shape of the through hole 11 and prevents or suppresses fraying when the tissue reinforcement material 100 is punched out by the medical instrument 200.

[0063] (Second Embodiment) Figure 14 is a schematic diagram showing a manufacturing method according to the second embodiment for forming the fused portion 40 of the tissue reinforcing material 100. In this embodiment, although the manufacturing method of the tissue reinforcing material 100 differs from that of the first embodiment, the tissue reinforcing material 100 itself is the same as in the first embodiment, so the description of the tissue reinforcing material 100 is omitted.

[0064] In this embodiment, as shown in Figure 14, multiple sheet members S containing biodegradable material are stacked, and multiple thermally conductive needle members 320a without a base portion 310 relative to the forming member 300 described in the first embodiment are pierced into the sheet members S to form through holes 11 in the sheet members S (S1). The multiple sheet members S containing biodegradable material that are stacked may each have different shape patterns of through holes 11. For example, from the shape patterns of through holes 11 of the main body portion 10 shown in Figures 3 to 6, sheet members S having through holes 11 arranged in two or more different shape patterns may be selected and stacked.

[0065] Then, with the needle member 320a punctured in the sheet member S, the needle member 320a is kept at a high temperature for a predetermined time. In this embodiment, the predetermined temperature can be set to any temperature that is above the melting point of the aforementioned fibers or the melting point of the aforementioned fibers. As a result, a fused portion 40 is formed in the sheet member S (S2). In this embodiment, the fused portion 40 is formed only in the vicinity portion 12 on either side (first surface and second surface) in the thickness direction X. After heating the needle member 320a, the sheet member S is cooled (S3), and the needle member 320a is removed from the sheet member S (S4).

[0066] As described above, in this embodiment, the fused portion 40 is formed in the vicinity portion 12 on either side in the thickness direction X. This configuration makes it easier to maintain the shape of the through hole 11.

[0067] When the needle member 320a is heated after passing it through the sheet member S to form a through hole 11, the needle member 320a is maintained at a temperature equal to or above the melting point of the fibers. With this configuration, the area around the through hole 11 can be melted to form a fused portion 40 in the fibers surrounding the through hole 11.

[0068] Furthermore, when the needle member 320a is passed through the sheet member S, the needle member 320a is passed through the sheet member S while multiple sheets of the sheet member S are stacked on top of each other. Then, the needle member 320a is kept at a high temperature for a predetermined time while it is in the state where it has passed through the sheet member S. By configuring it in this way, a tissue reinforcing material 100 can be obtained in which a fused portion 40 is formed on the fibers constituting the sheet member S.

[0069] It should be noted that the present invention is not limited to the embodiments described above, and various modifications are possible within the scope of the claims. In the first embodiment, it was explained that a preheated needle member 320 is used to puncture the sheet member S, but the fibers may be processed by needle punching to entangle them more than before the needle punching. This promotes entanglement between fibers, and it is expected that the rigidity of the main body 10 will be further increased when the fibers are fused together. In addition, in the second embodiment, the needle punching may be performed on the sheet member S before the fused portion 40 is formed. By performing needle punching, entanglement between fibers of multiple sheet members S can be promoted. Furthermore, by performing needle punching, multifilaments, which are bundles of multiple fibers, can be loosened, and entanglement between fibers can be promoted. By promoting entanglement between fibers, it becomes easier to form the fused portion 40 when the fibers are fused together, and the rigidity of the tissue reinforcement material 100 can be increased.

[0070] Furthermore, although the first embodiment described that a preheated needle member 320 is used to puncture the sheet member S to form the fused portion 40, the needle member 320 may be used to puncture the sheet member S with an unheated needle member 320 and then the base portion 310 may be heated. This configuration also makes it possible to form a fused portion 40 that increases the rigidity of the main body portion 10 and makes it less prone to twisting. Also, although the second embodiment described that the needle member 320a is used to puncture the sheet member S and then the needle member 320a is kept at a high temperature for a predetermined time, the needle member 320a may be used to heat the needle member 320a before puncturing the sheet member S.

[0071] (Experiment 1) The adhesion effect of the tissue reinforcement material was confirmed and explained below. In this experiment, the adhesion effect of the tissue reinforcement material was evaluated after measuring or calculating the pore size distribution rate, open area ratio, surface density, and thickness of the tissue reinforcement material for four comparative examples and thirteen examples. Note that for some of the comparative examples and examples, the experiment was conducted multiple times under the same conditions, and the number of samples listed in Tables 3 to 5 below differs. The pore size distribution rate was calculated by automatically analyzing the area of ​​the open area surrounded by fibers using image analysis software attached to the microscope, using magnified images (50x magnification) of the tissue reinforcement material taken with an optical microscope (digital microscope (VHX-2000, manufactured by Keyence Corporation)), under the analysis conditions described below. Each area was converted to an equivalent circle diameter (corresponding to the pore size), and the pore size distribution rate (%) for every 50 μm between pore sizes of 50 μm and 1000 μm was calculated. The overall pore size distribution rate (100%) is the area of ​​the rectangle in the magnified image acquired with an optical microscope (outer shape during image processing of the tissue reinforcement material), which can be calculated from the outer shape when there are no through holes, and the same applies to the overall open area rate. As for the analysis conditions, the brightness threshold in image analysis was set to 25, and no hole filling (processing to automatically fill small holes with an area below a specified value), no small particle removal, and no separation (processing to separate adjacent holes and recognize them as independent holes if their area is below a specified value when they are connected). The upper limit of the equivalent circle diameter was set to 1000 μm, which was determined from the upper limit of the sample size actually used in the experiment. Furthermore, the reason why the intermediate division of the sample was set to 400 μm, as shown below, is that the volume zone of the comparative example, which had a low adhesion effect, was 400 μm, and the volume zones of the example were 0-400 μm and 400 μm-1000 μm.

[0072] The pore size distribution ratio was calculated by determining the percentage of open areas relative to the total area of ​​the image (corresponding to the total area of ​​the mesh including the lines) based on the total area of ​​the open areas obtained by measuring the pore size distribution ratio.

[0073] The surface density was determined by measuring the weight of the tissue reinforcement material using a precision balance capable of measuring 0.01 mg, and then calculating the weight per unit area (g / m²). ２ It was converted to ).

[0074] The thickness was measured at five different locations on the tissue reinforcement material using a thickness gauge capable of measuring to 0.01 mm, and the average value was calculated.

[0075] For experiments on adhesion effects, a model of abdominal wall-cecal adhesion was created using rabbits. More specifically, under conditions without tissue reinforcement, a surgical procedure was performed by opening the abdomen of rabbits (strain: Japanese White, weight: 2.5-3.5 kg) under anesthesia. A 3 x 4 cm defect, including the peritoneal and muscular layers of the body cavity wall, was created on both the left and right lateral abdominal walls, 1 cm away from the midline. The abdominal wall and cecum were then fixed by suturing the four corners of a 2 x 3 cm area to create a suture pocket, which was then closed (abdominal closure). Under conditions with tissue reinforcement, the defect of the peritoneal and muscular layers of the body cavity wall was not performed. Instead, a 2 cm x 2.5 cm tissue reinforcement material was inserted between the suture pockets created by fixing the abdominal wall and cecum by suturing the four corners of a 2 x 3 cm area, and the suture pockets were closed (abdominal closure).

[0076] (Evaluation of adhesion score) Using this abdominal wall-cecal adhesion model, tissue reinforcement material was interposed between the abdominal wall and the cecum. Then, an autopsy was performed 3 days later (72 hours later), when the vulnerability of the postoperative biological tissue peaked, and the degree of adhesion at that time was evaluated according to the following grade.

[0077] Grade 0: No adhesions observed (detaches under its own weight) Grade 1: Adhesion that can be removed with slight blunt force without tissue damage Grade 2: Adhesion that can be removed with blunt force without tissue damage Grade 3: Adhesion that can be removed with blunt force, but with tissue damage Grade 4: Adhesion that can be removed with strong blunt force, but with tissue damage Grade 5: Adhesion that cannot be removed even with strong blunt force In this way, the abdominal wall tissue and cecal tissue were grasped with forceps, the adhesion sites were manually separated, and the adhesion score and adhesion effect were calculated for the following examples and comparative examples according to the judgment criteria described above.

[0078] (Evaluation of peel strength) The peel strength of each example and comparative example was evaluated by performing one of the following: measurement of the peak peel strength during vertical peeling, measurement of the average peel force during vertical peeling, or measurement of the average peel force during horizontal peeling.

[0079] (Peak Intensity of Vertical Dissection) For the peak intensity of vertical dissection, the entire circumference of the abdominal wall tissue was fixed to a silicone base with insect pins, and the end of the cecal tissue was clamped with a traction jig (clip). Then, a thread passed through the clip was attached to the hook of a push-pull gauge, and the push-pull gauge was pulled at a constant speed (3 mm / second) using a traction device, and the peak intensity of the force applied during vertical dissection was measured in real time from the measurement data (acquisition interval: 20 times / second).

[0080] (Average peeling force for vertical peeling) The average peeling force for vertical peeling was calculated by averaging the measurement data (acquisition interval 20 times / second) obtained from the peeling peak intensity of vertical peeling.

[0081] The adhesion effect was evaluated using ×, △, and ○, based on a comprehensive assessment of the adhesion score, the peak detachment strength of vertical delamination, and the average detachment force of vertical delamination. × indicates that the adhesion strength was less than the control (adhesion equivalent to wound healing in living tissue) when the adhesion score was less than 3, the peak detachment strength was less than 0.1 N, and the average detachment force was less than 0.03 N, resulting in no adhesion effect. △ indicates that the adhesion strength was between 3 and 5, the peak detachment strength was between 0.1 N and 0.6 N, and the average detachment force was between 0.03 N and 0.15 N, resulting in an adhesion effect that was comparable to the control or commercially available tissue reinforcement materials. ○ indicates that the adhesion strength was greater than that of commercially available tissue reinforcement materials when the adhesion score was greater than 5, the peak detachment strength was greater than 0.6 N, and the average detachment force was greater than 0.15 N, resulting in a high adhesion effect.

[0082] (Average dissection force for horizontal dissection) The average dissection force for horizontal dissection was measured by clamping the end of the abdominal wall tissue with a traction jig (clip) and fixing the thread attached to the traction jig to a base. The end of the cecal tissue was clamped with a traction jig (clip) fixed to a push-pull gauge. The push-pull gauge was pulled at a constant speed (3 mm / second) using a traction device, and measurement data (acquisition interval: 20 times / second) was acquired in real time, and the average value of the obtained measurement data (acquisition interval: 20 times / second) (average dissection force for horizontal dissection) was calculated.

[0083] Then, the average peeling force of the horizontal dissection was considered, and the adhesion effect was evaluated as follows using ×, △, and ○. × indicates that the average peeling force of the horizontal dissection was less than 0.04 N, and the adhesion strength was less than the control (adhesion equivalent to wound healing in living tissue), so it was evaluated as having no adhesion effect. △ indicates that when the average peeling force of the horizontal dissection was between 0.04 N and 0.12 N, the adhesion strength was comparable to the control or commercially available tissue reinforcement materials, so it was evaluated as having an adhesion effect. ○ indicates that when the average peeling force of the horizontal dissection was greater than 0.12 N, the adhesion strength was considered to be higher than that of commercially available tissue reinforcement materials, so it was evaluated as having a high adhesion effect.

[0084] Table 1 below shows the adhesion score results for Comparative Examples 1 to 4, and Table 2 shows the peel strength evaluation results for Comparative Examples 1, 2, and Examples 1 to 13. Tables 3 to 5 show the pore size distribution for the Examples and Comparative Examples, and Table 6 shows the number of data points, mean, standard deviation, and 99.7% confidence interval used to calculate the pore ratio of 399 μm or less and 400 μm or more in the Examples. The sample names and specifications used in Tables 4 and 5 are the same as those in Tables 1 and 2.

[0085] In this case, the "sample preparation conditions" listed in Tables 1 and 2 refer to the preparation conditions for the main body of the tissue reinforcement material used in Experiment 1. Regarding the comparative examples listed in Tables 1, 3 and Figure 15, Comparative Example 1 is an example in which no tissue reinforcement material was inserted as a control after creating an abdominal wall-cecal adhesion model. Comparative Example 2 is an example using NeoVeil Sheet (registered trademark) 015G type (manufactured by Gunze Medical Co., Ltd.). Comparative Example 3 is an example using NeoVeil Sheet (registered trademark) 03G type (manufactured by Gunze Medical Co., Ltd.). Comparative Example 4 is an example using Vicryl (registered trademark) mesh (manufactured by Johnson & Johnson Co., Ltd.). Furthermore, the sample preparation conditions for Examples 1 to 13 listed in Tables 2, 4, 5 and Figure 15 will be explained below. All tissue reinforcement materials listed in the examples were made from PGA polymer spun as the material. "Fabric classification" indicates the knitting method using the spun yarn, with Yokoami representing horizontal knitting (weft knitting) and Tateami representing warp knitting. Furthermore, "Number of filaments in the yarn" indicates the number of fiber bundles that make up one yarn. "Number of layers of fabric" indicates the number of layers of sheets created by either weft knitting or warp knitting used in the heat processing for creating through holes. "Needle punching" indicates whether needle punching was performed in the preliminary stage before the heat processing for creating through holes. "Heat processing" indicates the heating conditions (temperature, pressure, time, etc.) in the through-hole creation process.

[0086] The "size range" listed in Tables 3 to 5 refers to the ranges obtained by dividing the pore size distribution rate calculated by the measurement method described above into 50 μm units. "Sample No." indicates the identification number of the sample tested under the conditions of each example and comparative example, and the preparation conditions for each sample are the same for the same example. In the case of examples and comparative examples with multiple samples, the "average value" indicates the average value calculated from the pore size distribution rate of each sample.

[0087] The "Example Average" listed in Table 6 indicates that the average value, standard deviation (S.D.), and 99.7% confidence interval for the open area ratio were calculated based on the average value of each example. Furthermore, "Total Samples for Each Example" indicates that the average value, standard deviation (S.D.), and 99.7% confidence interval for the open area ratio were calculated from all samples in each example.

[0088]

[0089]

[0090]

[0091]

[0092]

[0093]

[0094] At this time, based on the pore size distribution rates listed in Tables 4 and 5, the pore size ratios for open holes with pore sizes of 0-399 μm and the pore size ratios for open holes with pore sizes of 400-1000 μm were calculated in the examples. Specifically, the sum of the pore size distribution rates for each pore size from 0 to 399 μm was used as the pore size ratio for open holes with pore sizes of 0-399 μm, and the sum of the pore size distribution rates for each pore size from 400-1000 μm was used as the pore size ratio for open holes with pore sizes of 400-1000 μm. Figure 15 is a graph plotting the examples (Example) and comparative examples (Reference) with the pore size ratios for 0-399 μm on the horizontal axis and the pore size ratios for 400-1000 μm on the vertical axis. From the measurement results of all the example samples listed in Tables 4 and 5, the measured range of porosity was found to be 2.2% (Example 4) to 19.3% (Example 10) for 0-399 μm, and 10.7% (Example 5) to 31.9% (Example 13) for 400 μm-1000 μm. When the measured range of each porosity is expressed with two significant figures, the lower limit is rounded down to the third digit, and the upper limit is rounded up to the third digit, the porosity for 0-399 μm is 2.2% to 20%, and the porosity for 400 μm-1000 μm is 10% to 32%.

[0095] Furthermore, the range of porosity for each of the examples and comparative examples was determined as shown in "All Samples of Examples" in Table 6. Based on the average value (Ave.) and standard deviation (S.D.) σ calculated from all samples of examples listed in Tables 4 and 5, and assuming a normal distribution for the data, the range of porosity was extended to a 99.7% confidence interval. When the significant figures were rounded down to two digits, with the lower limit truncated to the third digit and the upper limit rounded up to the third digit, the total area of ​​voids less than 400 μm was considered to be between 1.0% and 22% of the main body, and the ratio of the total area of ​​the main body to the total area of ​​voids between 400 μm and 1000 μm was considered to be between 7.3% and 40%. Note that, statistically, the lower limit of the total area of ​​voids less than 400 μm is a negative value, but this value cannot be negative in the actual tissue reinforcement material 100. Therefore, based on actual measurements of the tissue reinforcement material 100, we believe that the lower limit for the total area of ​​voids less than 400 μm is 1%, which translates to 1.0% when expressed to two significant figures.

[0096] Furthermore, as shown in the "Average Values ​​of Examples" in Table 6, the porosity was expanded to a value with a 99.7% confidence interval based on the average value (Ave.) and standard deviation (S.D.) σ calculated from the average values ​​of each example in Tables 4 and 5. At this time, using two significant figures, rounding down the third digit for the lower limit and rounding up the third digit for the upper limit, the total area of ​​voids less than 400 μm was considered to be between 1.0% and 25% of the main body, and the ratio of the total area of ​​the main body to the total area of ​​voids between 400 μm and 1000 μm was considered to be between 3.3% and 43%. Similar to when the porosity was calculated from all samples in the examples, the lower limit of the total area of ​​voids less than 400 μm is a negative value in statistical analysis, but since this value cannot be negative in the actual tissue reinforcement material 100, the lower limit is considered to be 1%, which is 1.0% when expressed with two significant figures. Furthermore, for all methods of calculating the porosity ratio, the lower limit of the 99.7% confidence interval is the average value (Ave.) minus three times the standard deviation (3σ), and the upper limit is the average value (Ave.) plus three times the standard deviation (3σ). Within this range, it can be said that the adhesion effect of the tissue reinforcement material 100 can be generally exerted. Based on these results, the inventors believe that through-holes of 0 to 400 μm serve as a scaffold for tissue regeneration, and through-holes of 400 μm to 1000 μm contribute to the adhesion between tissues.

[0097] Furthermore, the mass per unit area of ​​the main body 10, expressed with two significant figures, with the lower limit rounded down to the third digit and the upper limit rounded up to the third digit, is 17 g / m² from the surface density in Table 2. ２ 120g / m or more ２ Furthermore, based on the values ​​from the examples where the adhesion effect was positive, a more preferable value is 44 g / m². ２ 120g / m or more ２ It is believed to be the following:

[0098] Furthermore, when the ratio of the total area of ​​the void portion to the total area of ​​the main body portion 10 including the void portion is expressed with two significant figures, the lower limit is rounded down to the third digit, and the upper limit is rounded up to the third digit, it was found to be between 15% and 69%, and more preferably between 15% and 29%, based on the porosity ratio in Table 2.

[0099] Furthermore, it was found that the thickness of the main body 10 is between 0.15 mm and 0.57 mm, which is greater than or equal to the thickness shown in Table 2.

[0100] (Experiment 2) Next, we will explain the results of our investigation into the pressure resistance of tissue reinforcement material 100. In this experiment, under general anesthesia, the lower large intestine of a living pig was dissected with a linear stapler, the number of staples on the circular stapler was reduced, and the tissue reinforcement materials of Examples A to E and Comparative Examples B to D were sandwiched between them to perform a DST (Double Stapling Technique) anastomosis. Three days after the surgery, an autopsy was performed, the intestine was removed, and the burst pressure (burst intensity) was measured in vitro. To measure the burst pressure, an intestine fixation jig was attached to the opening of the removed intestine, closed, and the intestine was submerged in water. Air was then injected at a constant rate (1200 ml / h) using a peristaltic pump from the tube connection site on one side of the jig, and the pressure at which air leaked from the anastomosis site was defined as the burst pressure (mmHg). Table 7 below shows the specifications, volume density, and burst pressure of the example and comparative example used in this experiment. The volume density was calculated by measuring the weight and dimensions (length × width × thickness) of the sample. The porosity was calculated by analyzing the porosity of the wire diameter portion of the sample using μX rays under the following conditions. The apparatus used was a high-resolution desktop 3DX microscope, SKYSCAN 1272, with a pixel size of 3 μm and a tube voltage of 80 kV. The analysis mode was set to Morphological Operation for the (analysis target area) and Amplitude distribution analysis for (porosity analysis). Figure 16 is a graph showing the results of the example and comparative example, with the wire diameter porosity (%) on the horizontal axis and the vertical axis on the vertical axis. Note that for Table 7, explanations are omitted for parts that overlap with Tables 1 to 7 explained in Experiment 1. In the sample preparation conditions, "perforation" refers to the process of creating through holes by punching holes in the main sheet after heat treatment, and this was performed only in Comparative Example D. In Experiment 2, Comparative Example A is shown as a control case in which no tissue reinforcement material was inserted. Comparative Example B is an example using NeoVeil Sheet (registered trademark) 015G type (manufactured by Gunze Medical Co., Ltd.). Comparative Example C is an example using Vicryl (registered trademark) mesh (manufactured by Johnson & Johnson K.K.).Comparative Example D is an example in which NeoVeil Nano (registered trademark) D15 type (Gunze Medical Co., Ltd.) was subjected to heat processing and through-hole creation processing under the conditions described in Table 7. Examples A to E are all tissue reinforcement materials made from PGA polymer spun as the material and prepared under the sample preparation conditions described in Table 7.

[0101]

[0102] Figure 16 plots the Example and Reference examples on a graph with the porosity of the linear section on the horizontal axis and the volume density on the vertical axis, based on the results described in Table 7. Referring to the Comparative Example in Table 7, it was suggested that for improved pressure resistance, it is important that both the volume density and the porosity of the linear section of the structural reinforcement material are within a predetermined range. In this case, the volume density of the Example in Table 7, when expressed with two significant figures (rounded up to the third significant figure), is 0.15 g / cm³. ３ The following was found, and the void ratio excluding the through-holes in the main body 10 was found to be 50% or more. From these results, the inventors believe that the presence of many three-dimensional voids in the wire diameter portion of the mesh makes it easier for biological components such as fibrin and cells to adhere and proliferate when they invade, thus making it easier for the tissue reinforcement material 100 to function as a scaffold. Within this range, it can be said that the pressure-resistant effect of the tissue reinforcement material 100 can be generally achieved. In addition, by applying heat processing to the main body, the overall rigidity is increased, which prevents or suppresses the occurrence of twisting and shifting during use, and fraying when punched out with a stapler such as a medical device 200, making it easier to punch out. Therefore, it is possible to achieve both improved pressure resistance and improved operability.

[0103] The present invention is not limited to the embodiments described above, and various modifications are possible within the scope of the claims.

[0104] This application is based on Japanese Patent Application No. 2024-232159, filed on 27 December 2024, the disclosures of which are cited in their entirety by reference.

[0105] 10 Main body, 11 Through hole, 12 Nearby part, 13 Distal part, 40 Fused part, 41 First part, 42 Second part, 100 Tissue reinforcement material, X Thickness direction, YZ Plane direction.

Claims

1. The main body has a sheet-like thickness containing fibers made of biodegradable material, the main body has a plurality of through holes formed therein, and the fibers are gathered and fused together around the through holes, the volume density of the main body is 0.15 g / cm³ ３ A tissue reinforcing material, wherein the void ratio of the portion of the main body excluding the through-hole is 50% or more.

2. A tissue reinforcing material having a sheet-like main body containing fibers made of biodegradable material, wherein when the equivalent circle diameter calculated from the area of ​​the voids where the fibers are absent is measured in a plan view along the thickness direction of the main body, the size distribution ratio of the equivalent circle diameter of the voids is such that the total area of ​​the voids with an equivalent circle diameter of less than 400 μm is 1.0% or more and 25% or less of the total area of ​​the main body, and furthermore, the total area of ​​the voids with an equivalent circle diameter of 400 μm or more and 1000 μm or less is 3.3% or more and 43% or less of the total area of ​​the main body, as described in claim 1.

3. The tissue reinforcing material according to claim 1, wherein the distribution ratio of the equivalent circle diameter is such that the total area of ​​the voids with a pore diameter of less than 400 μm is 2.2% or more and 20% or less of the total area of ​​the main body, and furthermore, the total area of ​​the voids with a pore diameter of 400 μm or more and 1000 μm is 10% or more and 32% or less of the total area of ​​the main body.

4. The mass per unit area of ​​the main body is 17 g / m². ２ 120g / m or more ２ The tissue reinforcing material according to claim 1, which is as follows:

5. The mass per unit area of ​​the main body is 44 g / m². ２ 120g / m or more ２ The following is the tissue reinforcing material according to claim 4.

6. The tissue reinforcing material according to claim 1, wherein the ratio of the total area of ​​the voids to the total area of ​​the main body including the voids is 15% or more and 69% or less.

7. The tissue reinforcing material according to claim 6, wherein the ratio of the total area of ​​the voids to the total area of ​​the main body including the voids is 15% or more and 29% or less.

8. The tissue reinforcing material according to claim 1, wherein the thickness of the main body is 0.15 mm or more and 0.57 mm or less.

9. The tissue reinforcing material according to claim 1, wherein the main body is used by being sandwiched between the anastomoses of a living organ.

10. The tissue reinforcing material according to claim 1, wherein the fused portion comprises a portion in which the fibers are completely fused and a portion in which the area around the fibers is fused while maintaining the shape of the fibers.

11. The tissue reinforcing material according to claim 1, wherein the main body comprises a proximity portion located near the through hole in the planar direction of the main body, and a distal portion located further away from the through hole in the planar direction than the proximity portion, wherein the fibers are present at a higher density in the proximity portion than in the distal portion.

12. The tissue reinforcing material according to claim 11, wherein the fused portion is formed in the vicinity of the fused portion.

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